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1.
Future Oncol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643088

RESUMO

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.

2.
Hum Vaccin Immunother ; : 1-9, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34403292

RESUMO

Children with hematological malignancies are at increased risk of hepatitis B virus infection. This study assessed the immunogenicity and safety profile of HBV vaccination in pediatric hemato-oncological children. A nonrandomized interventional study was conducted from January 2017 to February 2020 in Shanghai, China. Seventy-three pediatric hemato-oncological children with hepatitis B surface antibody (anti-HBs) titers <10 mIU/ml were recruited. The participants received three doses of recombinant HBV vaccine according to the 0-, 1-, and 6- month immunization schedule. Adverse events following immunization and anti-HBs titers (at baseline, 1 month, and 6 months after inoculation) were recorded. Forty-three males and thirty females with median ages of 9.12 and 9.60 years, respectively, were included. The mean anti-HBs titer was 4.88 ± 2.61 mIU/ml, 893.12 ± 274.12 mIU/ml, and 711.45 ± 337.88 mIU/ml at baseline, one month, and six months after inoculation, respectively (P< .001). A total of fourteen adverse events following immunization were reported, and among them, 5 (6.85%), 5 (6.85%), and 4 (5.48%) events were reported after the first, second, and third inoculation, respectively (P= .927). In conclusions, the HBV vaccine is immunogenic and safe in children with hematological malignancies. It is worth noting that the anti-HBs titer was decreased at the 6-month follow-up, and periodic monitoring of the anti-HBs titer accompanied by timely booster vaccination should be carefully considered.Abbreviations: AEFI: Adverse events following immunization; HBV: Hepatitis B virus; Anti-HBs: Antibody against hepatitis B surface antigen; HBsAg: Hepatitis B surface antigen; APC: Antigen-presenting cell; HSCT: Hemopoietic stem cell transplantation; COVID-19: Corona Virus Disease 2019.

3.
Front Immunol ; 12: 642546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936059

RESUMO

Background: Vaccination is the best way to protect children under 5 years from death or disability. Children with biliary atresia (BA), which is the most common pediatric cholestatic end-stage liver disease (PELD), are more vulnerable to infectious diseases. However, the vaccination coverage and factors modulating vaccine responses in children with BA are largely unknown. Methods: In this study, 288 children (median age: 7 months) diagnosed with BA before liver transplantation were enrolled for the evaluation of vaccination status and the factors affecting the immune response to the hepatitis B (HBV) vaccine. Moreover, 49 BA children (median age: 4 months) were enrolled for flow cytometric analysis of CD4+ T cells and CD19+ B cell subsets and correlations with serum bile acid levels. Results: Generally, these children had very low routine vaccination rates for the meningococcal serogroup AC (Men AC) (41.2%), measles-mumps-rubella (MMR) (31.3%), poliomyelitis (Polio) (25.3%), hepatitis A (HAV) (25.0%), Japanese encephalitis (JE) (15.0%), diphtheria-tetanus-pertussis (DTP) (14.2%), meningococcal serogroup A (Men A) (13.5%) and varicella (VAR) (10.8%) vaccines, but not for the HBV (96.2%) and bacillus Calmette-Guérin (BCG) (84.7%) vaccines. Remarkably, 19.8% (57/288) of the patients had HBV infection. Out of 220 patients vaccinated for HBV, 113 (51.4%), 85 (38.6%) and 22 (10%) had one, two or three doses of the HBV vaccine, respectively. Furthermore, logistic regression analysis revealed that the bile acid level was an independent factor associated with poor HBV vaccine response (p = 0.03; OR = 0.394; 95% CI = 0.170-0.969). Immunophenotyping showed that bile acids were only negatively correlated with the CD19+CD27+IgG+ post-class-switched memory B cell ratio (p = 0.01). Conclusion: This study reveals the overall vaccination rates of routine vaccines in Chinese BA children are very low and the poor HBV vaccine responses are associated with bile acids, possibly via the inhibition of CD19+CD27+IgG+ post-class-switched memory B cell response. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR1800019165.


Assuntos
Linfócitos B/imunologia , Ácidos e Sais Biliares/sangue , Atresia Biliar , Linfócitos T CD4-Positivos/imunologia , Vacinas contra Hepatite B/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vacinação/estatística & dados numéricos
4.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097545

RESUMO

Epidermal electrophysiology is widely carried out for disease diagnosis, performance monitoring, human-machine interaction, etc. Compared with thick, stiff, and irritating gel electrodes, emerging tattoo-like epidermal electrodes offer much better wearability and versatility. However, state-of-the-art tattoo-like electrodes are limited in size (e.g., centimeters) to perform electrophysiology at scale due to challenges including large-area fabrication, skin lamination, and electrical interference from long interconnects. Therefore, we report large-area, soft, breathable, substrate- and encapsulation-free electrodes designed into transformable filamentary serpentines that can be rapidly fabricated by cut-and-paste method. We propose a Cartan curve-inspired transfer process to minimize strain in the electrodes when laminated on nondevelopable skin surfaces. Unwanted signals picked up by the unencapsulated interconnects can be eliminated through a previously unexplored electrical compensation strategy. These tattoo-like electrodes can comfortably cover the whole chest, forearm, or neck for applications such as multichannel electrocardiography, sign language recognition, prosthetic control or mapping of neck activities.

5.
Life Sci ; 215: 73-79, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30391650

RESUMO

AIMS: Ovarian cancer is the most leading cause of deaths among gynecologic malignancies, and Neuron-restrictive silencer factor (NRSF) can be upregulated or downregulated according to the type of tumor. However, the expression and function of NRSF in ovarian cancer is still unknown. MAIN METHODS: Expression of NRSF in normal ovary and ovarian cancer cells were evaluated by quantitative PCR (qPCR). NRSF expression in normal ovary and ovarian cancer tissue samples were examined by qPCR, western blotting and immunohistochemistry (IHC). MTT, colony formation, anchorage-independent growth assay were applied to examine the effect of NRSF on ovarian cancer cell proliferation. Bromodeoxyuridine (BrdUrd) labeling and flow cytometry assay were carried out to investigate the role of NRSF on cell cycle of ovarian cancer cells. Luciferase reporter assay and western blotting, immunofluorescence labeling were devoted to explore the mechanism by which NRSF contributes to proliferation of ovarian cancer cells. KEY FINDINGS: The results demonstrated that NRSF is significantly upregulated in ovarian cancer cells and tissues and negatively related with the survival of patients with ovarian cancer, and knockout of NRSF inhibit proliferation of ovarian cancer cells. Further analysis showed that NRSF can influence G1/S transition of cell cycle via regulating the transcription of Hippo pathway. SIGNIFICANCE: Herein, our study suggest that NRSF is associated with the progression of ovarian cancer, and NRSF may be a valuable early detection marker of ovarian cancer and inhibiting NRSF expression may be an effective method to treat ovarian cancer.


Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Ovarianas/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/genética , Western Blotting , Ciclo Celular/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Ovário/patologia , Reação em Cadeia da Polimerase , Taxa de Sobrevida
6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(9): 945-949, 2018 Sep 28.
Artigo em Chinês | MEDLINE | ID: mdl-30333284

RESUMO

OBJECTIVE: To explore the relationship between telomere length changes and age, and to provide data and reference for further study of geriatric medical problems.
 Methods: The healthy people over 20 years old were chosen as subject from several hospitals by random sampling method, and their peripheral blood samples were collected. The relative length of telomere was detected by quantitative real-time PCR, and the relationship between age and telomere length was analyzed by statistical software.
 Results: A total of 1 022 samples were obtained. There were significant differences in the relative telomere length among different age groups (F=21.492, P<0.001). Telomere length and age showed negative correlation (r=-0.325, P<0.001), the regression equation was y=-0.008x+1.772 (x for age, y for the average telomere length, P<0.001).
 Conclusion: The telomere length for peripheral blood leukocytes in healthy people varies between different age groups, suggesting that telomere length gradually decreases with age.


Assuntos
Telômero , Adulto , Fatores Etários , Humanos , Leucócitos Mononucleares , Análise de Regressão , Telômero/genética , Adulto Jovem
7.
J Mater Chem B ; 6(41): 6646-6659, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-32254873

RESUMO

In this work, we developed a novel core/shell chitosan (Cs)/hyaluronan (HA)-based hybrid nanoparticle, i.e. SNX@Cs-SNX/cHA, with good stability in the bloodstream and intracellular environment-sensitive drug delivery for breast cancer therapy. The core was a drug-loaded self-assembled micelle (SNX@Cs-SNX), and the shell was crosslinked to cysteine-conjugated hyaluronan (cHA) by disulfide bonds. Thanks to the combination of chemical bonding and physical encapsulation, the drug loading capacity of SNX@Cs-SNX/cHA nanoparticles was up to (14.6 ± 0.3)% in mass percentage. These stabilized core/shell nanoparticles were little affected by ionic strength (0.05-1.0 M sodium chloride solution), pH (6.8 and 7.4) and human plasma mimicking the bloodstream, but promptly disassembled by the multi-stimuli of glutathione (GSH), hyaluronidases (Hyals) and acidity (pH 5.0) mimicking the intracellular environment of breast cancer cells. In vitro 84% of the loaded drugs was released by GSH/Hyals/pH multi-stimuli within 72 h, as opposed to 28% at pH 7.4. SNX@Cs-SNX/cHA nanoparticles were highly endocytosed by both MCF-7 and MDA-MB-453 breast cancer cells and escaped from the endosomes/lysosomes as revealed by confocal laser scanning microscopy, showing a close IC50 value of 24.5 ng mL-1 and 41.0 ng mL-1 respectively to pure SNX. Thus, the SNX@Cs-SNX/cHA nanoparticle, which can not only increase the drug loading ability and stability in the blood circulation, but also control the fast intracellular drug delivery by GSH/Hyals/pH multi-stimuli in breast cancer cells, is a potential drug carrier for breast cancer therapy.

8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(11): 1293-1299, 2017 Nov 28.
Artigo em Chinês | MEDLINE | ID: mdl-29187657

RESUMO

OBJECTIVE: To build a social aging scale for healthy people, and get the accuracy and feasibility of the scale to judge the aging of healthy people on the basis of the empirical research.
 Methods: Stratified random sampling was conducted according to the nine different age groups, and the age-related social function information was collected for healthy people by using the scale, which was made in our own plant; the distribution of the score, the correlations between the score and age or telomere length were analyzed by statistical software.
 Results: A total of 2 297 subjects were collected for the analysis. The ratio of male to female was 0.8:1. Social function of aging score was in the range of 3.00-12.90; aging score of personal ability was in the range of 1.00-4.45; aging score of social participation was in the range of 1.00-4.52; and aging score of organizational communication was in the range of 1.00-5.00. The correlation coefficient of aging scores with age was 0.696 (P<0.001). The result of telomere length showed that the relative telomere length was 1.056±0.261. The telomere length in different groups were significantly different (F=35.803, P<0.001). The telomere length was negatively correlated with aging (r=-0.964, P<0.001) and social function of aging (r=-0.857, P<0.001), respectively.
 Conclusion: The scores of age-related social function, personal ability, social participation, and organizational communication are increased with age. The telomere length is negatively correlated to aging score. The scale is applicable to measure social function of aging, which can provide reference for evaluation of the comprehensive of aging.


Assuntos
Envelhecimento/fisiologia , Aptidão Física/fisiologia , Participação Social , Homeostase do Telômero/fisiologia , Fatores Etários , Pesquisa Empírica , Estudos de Viabilidade , Feminino , Humanos , Masculino
9.
J Clin Neurosci ; 43: 89-93, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28629681

RESUMO

Despite consistent evidence of a higher short-term risk of stroke mortality associated with ambient temperature, there are no findings on the association between extreme temperature and stroke. A total of 16,264 stroke hospital admissions were observed in three hospitals of Nanchang between 2008 and 2015. The case-crossover design was utilized for our study. Conditional logistic regression models were used to calculate the odds ratios. Extreme high temperature exposure during the 3days before the stroke was associated with both ischemic (OR=1.18; 95% CI: 1.07-1.36) and hemorrhagic stroke admissions (OR=1.34; 95% CI: 1.26-1.42) as compared to 3-day control periods (1-3days last week before the onset of stroke). Extreme low temperature was associated with hemorrhagic stroke admission (OR=1.42; 95% CI: 1.28-1.58) but not ischemic stroke (OR=1.06; 95% CI: 0.93-1.13). This study suggests that extreme high temperature might be a risk factor for both hemorrhagic and ischemic strokes, and that extreme low temperature might be a risk factor of hemorrhagic stroke. Further studies are necessary in order to clarify this relationship and provide evidence for stroke prevention.


Assuntos
Temperatura Baixa/efeitos adversos , Hospitalização/estatística & dados numéricos , Temperatura Alta/efeitos adversos , Hemorragias Intracranianas/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , China/epidemiologia , Estudos Cross-Over , Feminino , Humanos , Hemorragias Intracranianas/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Fatores de Risco , Acidente Vascular Cerebral/complicações
10.
Chem Biol Interact ; 264: 1-9, 2017 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-28088315

RESUMO

Paris saponins possess anticancer, anti-inflammatory, and antiviral effects. However, the anticancer effect of Paris saponins has not been well elucidated and the mechanisms underlying the potential function of Paris saponins in cancer therapy are needed to be further identify. In this study, we report that saponin compounds isolated from Paris polyphylla exhibited antitumor activity against breast cancer cell lines, MCF-7 and MDA-MB-231. Paris saponin XA-2 induced apoptosis in both cell lines, as evidenced by the activation of caspases and cleavage of Poly (ADP-ribose) polymerase. The ability of XA-2 to induce autophagy was confirmed by acridine orange staining, accumulation of autophagosome-bound Long chain 3 (LC3)-II, and measurement of autophagic flux. XA-2-induced autophagy was observed to promote apoptosis by the combined treatment of breast cancer cell lines with XA-2 and autophagy inhibitors 3-methyladenine and bafilomycin A1, respectively. Moreover, we report a decrease in the levels of Akt/mTOR signaling pathway proteins, such as the phosphorylated forms of Akt, mTOR, P70S6K, and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). Taken together, these results provide important insights explaining the anticancer activity of Paris saponins and the potential development of XA-2 as a new therapeutic agent.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/química , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Mama/efeitos dos fármacos , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Liliaceae/química , Saponinas/isolamento & purificação , Serina-Treonina Quinases TOR/metabolismo
11.
J Exp Clin Cancer Res ; 35(1): 161, 2016 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-27716441

RESUMO

BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumor, but treatment is difficult and prognosis remains poor. Recently, large-dose chemotherapy has been shown to improve outcome but this approach can cause many side effects. Minimizing the dose of chemotherapeutic drugs and optimizing their curative effects is a current goal in the management of osteosarcoma patients. METHODS: In our study, trypan blue dye exclusion assay was performed to investigate the optimal conditions for the sensitization of osteosarcoma U2OS cells. Cellular uptake of the fluorophores Lucifer Yellow CH dilithium salt and Calcein was measured by qualitative and quantitative methods. Human MTX ELISA Kit and MTT assay were used to assess the outcome for osteosarcoma U2OS cells in the present of shock wave and methotrexate. To explore the mechanism, P2X7 receptor in U2OS cells was detected by immunofluorescence and the extracellular ATP levels was detected by ATP assay kit. All data were analyzed using SPSS17.0 statistical software. Comparisons were made with t test between two groups. RESULTS: Treatment of human osteosarcoma U2OS cells with up to 450 shock wave pulses at 7 kV or up to 200 shock wave pulses at 14 kV had little effect on cell viability. However, this shock wave treatment significantly promoted the uptake of Calcein and Lucifer Yellow CH by osteosarcoma U2OS cells. Importantly, shock wave treatment also significantly enhanced the uptake of the chemotherapy drug methotrexate and increased the rate of methotrexate-induced apoptosis. We found that shock wave treatment increased the extracellular concentration of ATP and that KN62, an inhibitor of P2X7 receptor reduced the capacity methotrexate-induced apoptosis. CONCLUSIONS: Our results suggest that shock wave treatment promotes methotrexate-induced apoptosis by altering cell membrane permeability in a P2X7 receptor-dependent manner. Shock wave treatment may thus represent a possible adjuvant therapy for osteosarcoma.


Assuntos
Trifosfato de Adenosina/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Ósseas/metabolismo , Metotrexato/farmacologia , Osteossarcoma/metabolismo , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Tratamento por Ondas de Choque Extracorpóreas , Fluoresceínas/metabolismo , Humanos , Osteossarcoma/terapia , Receptores Purinérgicos P2X7/metabolismo
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(4): 422-6, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27241155

RESUMO

OBJECTIVE: To build a physiological aging scale for healthy people.
 METHODS: We collected age-related physiologic items through literature screening and expert interview. Two rounds of Delphi were implemented. The importance, feasibility and the degree of authority for the physiological index system were graded. Using analytic hierarchy process, we determined the weight of dimensions and items.
 RESULTS: Using Delphy mothod, 17 physiological and other professional experts offered the results as follow: coefficient of expert authorities Cr was 0.86±0.03, coordination coefficients for the first and second round were 0.264(χ2=229.691, P<0.001) and 0.293(χ2=228.474,P<0.001), respectively. The consistency was good. The aging scale for healthy people included 3 dimensions, namely physical form, feeling movement and functional status. Each dimension had 8 items. The weight coefficients for the 3 dimensions were 0.54, 0.16, and 0.30, respectively. The Cronbach's α coefficient of the scale was 0.893, the reliability was 0.796, and the variance of the common factor was 58.17%.
 CONCLUSION: The improved Delphi method or physiological aging scale is satisfied, which can provide reference for the evaluation of aging.


Assuntos
Envelhecimento/fisiologia , Técnica Delfos , Humanos , Reprodutibilidade dos Testes
13.
Zhonghua Fu Chan Ke Za Zhi ; 43(6): 425-8, 2008 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19035136

RESUMO

OBJECTIVE: To investigate the pattern of disease relapse and prognostic risk factor of patients with cervical carcinoma and pelvic lymph node metastasis. METHODS: A total of 124 cases of International Federation of Gynecology and Obstetrics (FIGO) Ib1-IIa cervical carcinoma with pelvic node metastasis who were treated at the Cancer Center of Sun Yat-sen University during January 1994 to December 2001 were selected for this study. Prognosis and recurrence were retrospectively analyzed using the clinico-pathological data RESULTS: The overall 5 year survival and 5 year disease-free survival were 63.3% and 61.4%, respectively. Overall recurrence rate was 39.5% (49/124), among which intra-pelvic relapse (61.0%, 25/41) was significantly more common than extra-pelvic relapse (31.7%,13/41; P=0.008). Multivariate analysis identified involvement of common iliac node as an independent prognostic factor (P=0.035). According to this factor, node-positive patients could be divided into low risk group (without common iliac node involvement, 104 cases) and high risk group (with common iliac node involvement, 20 cases). The 5 year disease-free survival were 69.4% and 24.5% respectively, with a significant difference (P=0.003). Intra-pelvic relapse was observed in 22.1% (23/104) of low risk and 25.0% (5/20) of high risk group respectively, with no significant difference (P>0.05). However extra-pelvic relapse was seen in 7.7% (8/104) of low risk and 40.0% (8/20) of high risk group, with a significant difference (P<0.01). CONCLUSIONS: Common iliac node involvement is a significant factor influencing the prognosis of patients with cervical carcinoma and pelvic lymph node metastasis. Patients with positive common iliac nodes have significantly decreased 5 year disease-free survival and higher extra-pelvic disease recurrence rates compared with those whose common iliac nodes are negative. These findings provide important data for design of individualized treatment mode.


Assuntos
Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Metástase Linfática , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Pelve/patologia , Pelve/cirurgia , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia
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