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1.
Healthcare (Basel) ; 12(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38610125

RESUMEN

Non-pharmaceutical midwifery techniques, including perineal warm compresses, to improve maternal outcomes remain controversial. The aims of this study are to assess the effects of perineal warm compresses on reducing perineal trauma and postpartum perineal pain relief. This systematic review included randomized controlled trials (RCTs). We searched seven bibliographic databases, three RCT register websites, and two dissertation databases for publications from inception to 15 March 2023. Chinese and English publications were included. Two independent reviewers conducted the risk of bias assessment, data extraction, and the evaluation of the certainty of the evidence utilizing the Cochrane risk of bias 2.0 assessment criteria, the Review Manager 5.4, and the online GRADEpro tool, respectively. Seven RCTs involving 1362 primiparous women were included. The combined results demonstrated a statistically significant reduction in the second-, third- and/or fourth- degree perineal lacerations, the incidence of episiotomy, and the relief of the short-term perineal pain postpartum (within two days). There was a potential favorable effect on improving the integrity of the perineum. However, the results did not show a statistically significant supportive effect on reducing first-degree perineal lacerations and the rate of perineal lacerations requiring sutures. In summary, perineal warm compresses effectively reduced the second-, third-/or fourth-degree perineal trauma and decreased the short-term perineal pain after birth.

2.
Cell Biochem Funct ; 42(2): e3961, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38425124

RESUMEN

A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , MicroARNs/metabolismo
3.
J Proteomics ; 296: 105113, 2024 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-38346667

RESUMEN

This study aimed to investigate the different regulatory mechanisms of euryhaline fish under regular hyperosmotic and extreme hyperosmotic stress. The OmB (Oreochromis mossambicus brain) cells were exposed to three treatments: control, regular hyperosmotic stress and extreme hyperosmotic stress. After 12 h exposure, proteomics, metabolomics analyses and integrative analyses were explored. Both kinds of stress lead to lowering cell growth and morphology changes, while under regular hyperosmotic stress, the up-regulated processes related with compatible organic osmolytes synthesis are crucial strategy for the euryhaline fish cell line to survive; On the other hand, under extreme hyperosmotic stress, the processes related with cell apoptosis and cell cycle arrest are dominant. Furthermore, down-regulated pyrimidine metabolism and several ribosomal proteins partially participated in the lowered cell metabolism and increased cell death under both kinds of hyperosmotic stress. The PI3K-Akt and p53 signaling pathways were involved in the stagnant stage of cell cycles and induction of cell apoptosis under both kinds of hyperosmotic stress. However, HIF-1, FoxO, JAK-STAT and Hippo signaling pathways mainly contribute to disrupting the cell cycle, metabolism and induction of cell apoptosis under extreme hyperosmotic stress. SIGNIFICANCE: In the past, the research on fish osmoregulation mainly focused on the transcription factors and ion transporters of osmoregulation, the processes between osmotic sensing and signal transduction, and the associations between signaling pathways and regulation processes have been poorly understood. Investigating fish cell osmoregulation and potential signal transduction pathways is necessary. With the advancements in omics research, it is now feasible to investigate the relationship between environmental stress and molecular responses. In this study, we aimed to explore the signaling pathways and substance metabolism mode during hyper-osmoregulation in OmB cell line, to reveal the key factors that are critical to cell osmoregulation.


Asunto(s)
Osmorregulación , Tilapia , Animales , Tilapia/metabolismo , Proteómica , Fosfatidilinositol 3-Quinasas/metabolismo , Adaptación Psicológica
4.
BMC Neurol ; 24(1): 7, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167007

RESUMEN

OBJECTIVE: To investigate the potential diagnostic and prognostic implications of inflammatory cytokine levels in the cerebrospinal fluid (CSF) of patients with spontaneous intracerebral hemorrhage (SICH) upon their initial hospital admission. METHODS: Our cohort included 100 patients diagnosed with acute SICH, presenting to the Department of Neurosurgery. Additionally, we recruited 50 individuals without central nervous system (CNS) pathology, treated concurrently at our facility, as controls. CSF samples, collected upon hospital entry, were quantitatively assessed for 10 inflammatory cytokines using the Mesoscale Discovery Platform (MSD, Rockville, MD, USA) electrochemiluminescence technology, followed by validation through enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a marked elevation of IL-6, IL-8, IL-10, and TNF-α in the CSF of the SICH subgroup compared to controls. Higher Glasgow Coma Scale (GCS) scores in SICH patients corresponded with lower CSF concentrations of IL-6, IL-8, IL-10, and TNF-α, indicating an inverse relationship. Notably, CSF inflammatory cytokine levels were consistently higher in SICH patients with hydrocephalus than in those without. Increases in IL-6, IL-8, IL-10, and TNF-α in the CSF were notably more pronounced in the poor prognosis group (Glasgow Outcome Scale, GOS 1-3) compared to those with a favorable prognosis (GOS 4-5). The AUC values for these cytokines in predicting SICH prognosis were 0.750, 0.728, 0.717, and 0.743, respectively. CONCLUSIONS: Initial CSF levels of IL-6, IL-8, IL-10, and TNF-α upon admission provide significant insights into the severity of neural damage and are robust indicators for prognosis in SICH patients.


Asunto(s)
Citocinas , Interleucina-10 , Humanos , Factor de Necrosis Tumoral alfa , Interleucina-6 , Interleucina-8/líquido cefalorraquídeo , Hemorragia Cerebral/diagnóstico , Pronóstico
5.
J Environ Public Health ; 2023: 3414849, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38115991

RESUMEN

In the process of China's rapid urbanization, the health level of residents has been improved to a great extent. However, with the expansion of urban scale and spatial restructuring, a series of urban environmental problems have posed new challenges to public health. However, the impact of the built environment on residents' health is controversial, and the applicability of the conclusions based on western urban sprawl in China is not clear enough. In addition, the exploration of the impact path of the built environment on health is still not comprehensive and in-depth. Based on the China Labor Dynamics Survey (CLDS) in 2016 and relevant statistical yearbook data, this study explored the impact of the built environment at community and urban scale on residents' health and its age heterogeneity and further explored the mediating role of physical exercise, neighborhood support, and community safety. According to the research, the urban and community-built environment has significant impacts on residents' health, and the impact is significantly different at different scales. In addition, there is a significant difference in the impact of built environment factors on residents' health among populations with different life cycles. From the perspective of the impact path, greening coverage can improve residents' self-rated health by enhancing the perceived safety of living in the community. In contrast, the high community population density will not only weaken the degree of neighborhood support but also reduce the perception level of community residential safety, thus damaging residents' health. In short, from the perspective of environmental intervention, the previously mentioned results put forward possible suggestions on strengthening the construction of a healthy living environment so as to maximize the health effectiveness of cities and communities.


Asunto(s)
Entorno Construido , Humanos , China/epidemiología , Ciudades , Encuestas y Cuestionarios , Población Urbana
6.
J Colloid Interface Sci ; 651: 200-210, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37542895

RESUMEN

Excessive CO2 emissions and the resultant global warming present significant environmental challenges, posing threats to human health and public safety. Metal-organic frameworks (MOFs), known for their high specific area and large porosity, hold the promise for CO2 capture. However, a major obstacle is the low loading mass of MOFs and the limited interface affinity and compatibility between MOFs and substrates. In this study, we present an electrospinning-assisted in-situ synthesis dual metallic framework strategy for preparing flexible Zn/Co-ZIF nanofibrous membranes (NFMs). This method achieves the high loading mass of MOFs and introduces abundant Lewis basic sites, thereby enhancing the CO2 adsorption. The dual metallic Zn/Co-ZIF NFMs exhibit remarkable features, including high MOF loading mass (70.23 wt%), high specific surface area (379.63 m2g-1), large porosity (92.34 %), high CO2 adsorption capacity (4.43 mmol/g), high CO2/N2 adsorption selectivity (37), and high CO2/CH4 adsorption selectivity (31). Moreover, the dual metallic Zn/Co-ZIF NFMs demonstrate robust structural stability and durability attributed to the excellent interface affinity between MOFs and NFMs, retaining 96.56 % of their initial capacity after 10 adsorption-desorption cycles. This work presents a prospective direction for developing flexible dual metallic MOF NFMs for the efficient capture of CO2.

7.
Sheng Wu Gong Cheng Xue Bao ; 39(8): 3236-3252, 2023 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-37622358

RESUMEN

Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.


Asunto(s)
Escherichia coli , NAD , Escherichia coli/genética , Ácido Succínico , Ácido Acético , Adenosina Trifosfato
8.
Biol Direct ; 18(1): 19, 2023 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-37088822

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. METHODS: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. RESULTS: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. CONCLUSION: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.


Asunto(s)
Neoplasias Colorrectales , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proliferación Celular/genética , Carcinogénesis/genética , ARN , Regulación Neoplásica de la Expresión Génica
9.
FASEB J ; 37(4): e22839, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36946075

RESUMEN

Nearly half a million women are diagnosed with cervical cancer (CC) each year, with the incidence of CC stabilizing or rising in low-income and middle-income countries. Cancer cells use metabolic reprogramming to meet the needs of rapid proliferation, known as the Warburg effect, but the mechanism of the Warburg effect in CC remains unclear. microRNAs (miRNAs) have a wide range of effects on gene expression and diverse modes of action, and they regulate genes for metabolic reprogramming. Dysregulation of miRNA expression leads to metabolic abnormalities in tumor cells and promotes tumorigenesis and tumor progression. In this study, we found that miR-145 was negatively correlated with metabolic reprogramming-related genes and prevented the proliferation and metastasis of CC cell lines by impeding aerobic glycolysis. A dual-luciferase reporter assay showed that miR-145 can bind to the 3'-untranslated region (3'-UTR) of MYC. Chromatin Immunoprecipitation-quantitative real-time PCR indicated that MYC was involved in the regulation of glycolysis-related genes. In addition, miR-145 mimics significantly suppressed the growth of CC cell xenograft tumor, prolonged the survival time of mice, and dramatically silenced the expression of tumor proliferation marker Ki-67. Therefore, the results suggested that miR-145 affects aerobic glycolysis through MYC, which may be a potential target for the treatment of CC.


Asunto(s)
MicroARNs , Neoplasias del Cuello Uterino , Humanos , Femenino , Animales , Ratones , Línea Celular Tumoral , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores de Tumor/metabolismo , Proliferación Celular/genética , Glucólisis/genética , Regulación Neoplásica de la Expresión Génica
10.
Anal Chim Acta ; 1253: 341030, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36965987

RESUMEN

Mobile sensing enabled by MS2 technology, which integrates microfluidic and smartphone components, has seen many applications in recent years. In this direction, we developed an MS2 platform (an integrated kit) for nucleic acid assay, which included a chitosan-modified minimalistic microfluidic chip (CM3-chip), a smartphone-based fluorescence detector (SF-detector), an APP for imaging and analysis, reagents, and accessories. Once the lysed sample was loaded into the CM3-chip modified by 1% concentration and 200-260 kDa molecular weight of chitosan, the following assay can be completed in approximately 1 h. The Mkit can detect 3 × 10° copies µL-1 of plasmid DNA and its polymerase chain reaction (PCR) efficiency was 96.8%. The CM3-chip equipped for the Mkit can enrich nucleic acid from the pH = 5 of lysis buffer, instead of using conventional adsorption mediums such as the magnetic beads and silica gel membranes, which could result in unexpected impurity residuals and tedious cleaning operations. In addition, the performance of the Mkit equipped with the pristine chip was demonstrated to perform poorer than that coupled with the CM3-chip in which the enriched nucleic acid can be all used for "in-situ PCR". The universality, selectivity, and user-friendliness of the Mkit were also validated. We finally demonstrated the feasibility of the Mkit for testing artificially prepared infected samples. H5N6 and IAV-infected saliva samples provided the limits of detection of 5 × 102 copies mL-1 and 3.24 × 102 copies mL-1 per chamber, respectively. The streamlined assay and compact device should enable the great potential of the Mkit in research and potential diagnostic uses.


Asunto(s)
Quitosano , Técnicas Analíticas Microfluídicas , Ácidos Nucleicos , Microfluídica , Teléfono Inteligente , Quitosano/química , ADN/genética , Ácidos Nucleicos/análisis , Técnicas de Amplificación de Ácido Nucleico/métodos
11.
Bioresour Bioprocess ; 10(1): 25, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38647943

RESUMEN

Improving the growth status of Aspergillus oryzae is an efficient way to enhance L-malate production. However, the growth mechanism of filamentous fungi is relatively complex, which limits A. oryzae as a cell factory to produce L-malate industrially. This study determined the relationship between growth status and L-malate production. The optimal ranges of colony diameter, percentage of vegetative mycelia, and pellet number of A. oryzae were determined to be 26-30 mm, 35-40%, and 220-240/mL, respectively. To achieve this optimum range, adaptive evolution was used to obtain the evolved strain Z07 with 132.54 g/L L-malate and a productivity of 1.1 g/L/h. Finally, a combination of transcriptome analysis and morphological characterization was used to identify the relevant pathway genes that affect the growth mechanism of A. oryzae. The strategies used in this study and the growth mechanism provide a good basis for efficient L-malate production by filamentous fungi.

12.
Anim Nutr ; 10: 86-98, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35647324

RESUMEN

A two-factor (2 × 3) orthogonal test was conducted to investigate the effects of dietary myo-inositol (MI) on the osmoregulation and carbohydrate metabolism of euryhaline fish tilapia (Oreochromis niloticus) under sustained hypertonic stress (20 practical salinity units [psu]). 6 diets containing either normal carbohydrate (NC, 30%) or high carbohydrate (HC, 45%) levels, with 3 levels (0, 400 and 1,200 mg/kg diet) of MI, respectively, were fed to 540 fish under 20 psu for 8 weeks. Dietary MI supplementation significantly improved growth performance and crude protein content of whole fish, and decreased the content of crude lipid of whole fish (P < 0.05). Curled, disordered gill lamella and cracked gill filament cartilage were observed in the gill of fish fed diets without MI supplementation. The ion transport capacity in gill was significantly improved in the 1,200 mg/kg MI supplementation groups compared with the 0 mg/kg MI groups (P < 0.05). Moreover, the contents of Na+, K+, Cl- in serum were markedly reduced with the dietary MI supplementation (P < 0.05). The fish fed 1,200 mg/kg MI supplementation had the highest MI content in the gills and the lowest MI content in the serum (P < 0.05). Additionally, the fish fed with 1,200 mg/kg MI supplementation had the highest MI synthesis capacity in gills and brain (P < 0.05). Dietary MI markedly promoted the ability of carbohydrate metabolism in liver (P < 0.05). Moreover, fish in the 1,200 mg/kg MI groups had the highest antioxidant capacity (P < 0.05). This study indicated that high dietary carbohydrate would intensify stress, and impair the ability of osmoregulation in tilapia under a long-term hypersaline exposure. The supplementation of MI at 1,200 mg/kg in the high carbohydrate diet could promote carbohydrate utilization and improve the osmoregulation capacity of tilapia under long-term hypertonic stress.

13.
Vaccines (Basel) ; 10(4)2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35455313

RESUMEN

MHC-I antigen processes and presentation trigger host-specific anti-viral cellular responses during infection, in which epitope-recognizing cytotoxic T lymphocytes eliminate infected cells and contribute to viral clearance through a cytolytic killing effect. In this study, Hantaan virus (HTNV) GP-derived 9-mer dominant epitopes were obtained with high affinity to major HLA-I and H-2 superfamilies. Further immunogenicity and conservation analyses selected 11 promising candidates, and molecule docking (MD) was then simulated with the corresponding MHC-I alleles. Two-way hierarchical clustering revealed the interactions between GP peptides and MHC-I haplotypes. Briefly, epitope hotspots sharing good affinity to a wide spectrum of MHC-I molecules highlighted the biomedical practice for vaccination, and haplotype clusters represented the similarities among individuals during T-cell response establishment. Cross-validation proved the patterns observed through both MD simulation and public data integration. Lastly, 148 HTNV variants yielded six types of major amino acid residue replacements involving four in nine hotspots, which minimally influenced the general potential of MHC-I superfamily presentation. Altogether, our work comprehensively evaluates the pan-MHC-I immunoreactivity of HTNV GP through a state-of-the-art workflow in light of comparative immunology, acknowledges present discoveries, and offers guidance for ongoing HTNV vaccine pursuit.

14.
Front Immunol ; 13: 846402, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35281055

RESUMEN

Background: Increasing evidence shows that the ubiquitin-proteasome system has a crucial impact on lung adenocarcinoma. However, reliable prognostic signatures based on ubiquitination and immune traits have not yet been established. Methods: Bioinformatics was performed to analyze the characteristic of ubiquitination in lung adenocarcinoma. Principal component analysis was employed to identify the difference between lung adenocarcinoma and adjacent tissue. The ubiquitin prognostic risk model was constructed by multivariate Cox regression and least absolute shrinkage and selection operator regression based on the public database The Cancer Genome Atlas, with evaluation of the time-dependent receiver operating characteristic curve. A variety of algorithms was used to analyze the immune traits of model stratification. Meanwhile, the drug response sensitivity for subgroups was predicted by the "pRRophetic" package based on the database of the Cancer Genome Project. Results: The expression of ubiquitin genes was different in the tumor and in the adjacent tissue. The ubiquitin model was superior to the clinical indexes, and four validation datasets verified the prognostic effect. Additionally, the stratification of the model reflected distinct immune landscapes and mutation traits. The low-risk group was infiltrating plenty of immune cells and highly expressed major histocompatibility complex and immune genes, which illustrated that these patients could benefit from immune treatment. The high-risk group showed higher mutation and tumor mutation burden. Integrating the tumor mutation burden and the immune score revealed the patient's discrepancy between survival and drug response. Finally, we discovered that the drug targeting ubiquitin and proteasome would be a beneficial prospective treatment for lung adenocarcinoma. Conclusion: The ubiquitin trait could reflect the prognosis of lung adenocarcinoma, and it might shed light on the development of novel ubiquitin biomarkers and targeted therapy for lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Estudios Prospectivos , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Transcriptoma , Ubiquitinación , Ubiquitinas/metabolismo
15.
Int Immunol ; 34(6): 313-325, 2022 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-35192720

RESUMEN

Ebolavirus (EBOV) causes an extremely high mortality and prevalence disease called Ebola virus disease (EVD). There is only one glycoprotein (GP) on the virus particle surface, which mediates entry into the host cell. Major histocompatibility complex (MHC) class-I restricted cluster of differentiation 8 (CD8+) T cell responses are important antiviral immune responses. Therefore, it is of great importance to understand EBOV GP-specific MHC class-I restricted epitopes within immunogenicity. In this study, computational approaches were employed to predict the dominant MHC class-I molecule epitopes of EBOV GP for mouse H2 and major alleles of human leukocyte antigen (HLA) class-I supertypes. Our results yielded 42 dominant epitopes in H2 haplotypes and 301 dominant epitopes in HLA class-I haplotypes. After validation by enzyme-linked immunospot (ELISpot) assay, in-depth analyses to ascertain their nature of conservation, immunogenicity, and docking with the corresponding MHC class-I molecules were undertaken. Our study predicted MHC class-I restricted epitopes that may aid the advancement of anti-EBOV immune responses. An integrated strategy of epitope prediction, validation and comparative analyses was postulated, which is promising for epitope-based immunotherapy development and application to viral epidemics.


Asunto(s)
Ebolavirus , Animales , Epítopos de Linfocito T , Glicoproteínas , Antígenos HLA , Antígenos de Histocompatibilidad Clase I , Ratones
16.
Int Immunopharmacol ; 103: 108505, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34995995

RESUMEN

BACKGROUND: Taxol-resistance gene 1 (TXR1) is closely correlated with the paclitaxel resistance in the cancer chemotherapy. However, due to the lack of monoclonal antibodies (mAbs) with strong specificity and high sensitivity, little information is found about TXR1 target-related tumor therapy. METHODS: We developed an TXR1 recombinant DNA vaccine by inserting TXR1 DNA sequence into lysosome-associated membrane protein 1 (LAMP1). Adaptive immune responses were assessed by indirect enzyme-linked immunosorbent assay (ELISA), Enzyme-linked immunospot test (ELISpot), and cytotoxic T-lymphocyte (CTL) cytotoxicity. RESULTS: The pGEX4T-1-TXR1 reconstructed prokaryotic expression plasmid was constructed for producing high-purity TXR1 protein. Subsequently, a total of four mAbs for TXR1 and two PcAbs were successfully constructed and identified. We further found that TXR1 was highly expressed in breast cancer tissue than normal controls. Therefore, we constructed four tumor vectors, pVAX1-LAMP/TXR1, pVAX1-LAMP, pVAX1/TXR1 and pVAX1, for immunization. After three times of immunization, ELISpot data showed that single peptide 6,9,11 could stimulate T cells secreting IFN-γ in pVAX1-LAMP/TXR1 group. Moreover, the number of specific T cells and immune response effects significantly increased comparing to the pVAX1-LAMP control group. In addition, cytotoxicity showed that when the effect to target ratio was 40:l the killing effect of pVAX1-LAMP/TXR1 group was significantly higher than the pVAX1-TXR1 group. CONCLUSION: Our results provides new evidence for the TXR1 related tumor immunology and aids the early prevention of cancer.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Vacunas de ADN , Animales , Anticuerpos Antivirales , Vacunas contra el Cáncer/genética , ADN , Humanos , Ratones , Ratones Endogámicos BALB C , Neoplasias/terapia
17.
Int J Biol Sci ; 18(2): 507-521, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35002506

RESUMEN

Enhanced aerobic glycolysis constitutes an additional source of energy for tumor proliferation and metastasis. Human papillomavirus (HPV) infection is the main cause of cervical cancer (CC); however, the associated molecular mechanisms remain poorly defined, as does the relationship between CC and aerobic glycolysis. To investigate whether HPV 16/18 E6/E7 can enhance aerobic glycolysis in CC, E6/E7 expression was knocked down in SiHa and HeLa cells using small interfering RNA (siRNA). Then, glucose uptake, lactate production, ATP levels, reactive oxygen species (ROS) content, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were evaluated. RNA-seq was used to probe the molecular mechanism involved in E6/E7-driven aerobic glycolysis, and identified IGF2BP2 as a target of E6/E7. The regulatory effect of IGF2BP2 was confirmed by qRT-PCR, western blot, and RIP assay. The biological roles and mechanisms underlying how HPV E6/E7 and IGF2BP2 promote CC progression were confirmed in vitro and in vivo. Human CC tissue microarrays were used to analyze IGF2BP2 expression in CC. The knockdown of E6/E7 and IGF2BP2 attenuated the aerobic glycolytic capacity and growth of CC cells, while IGF2BP2 overexpression rescued this effect in vitro and in vivo. IGF2BP2 expression was higher in CC tissues than in adjacent tissues and was positively correlated with tumor stage. Mechanistically, E6/E7 proteins promoted aerobic glycolysis, proliferation, and metastasis in CC cells by regulating MYC mRNA m6A modifications through IGF2BP2. We found that E6/E7 promote CC by regulating MYC methylation sites via activating IGF2BP2 and established a link between E6/E7 and the promotion of aerobic glycolysis and CC progression. Blocking the HPV E6/E7-related metabolic pathway represents a potential strategy for the treatment of CC.


Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Proteínas de Unión al ARN/genética , Proteínas Represoras/genética , Neoplasias del Cuello Uterino/patología , Efecto Warburg en Oncología , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Terapia Genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Metiltransferasas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Infecciones por Papillomavirus/virología , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Neoplasias del Cuello Uterino/virología , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Acad Med ; 97(3): 380-384, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34554942

RESUMEN

PROBLEM: Graduate medical education programs and national organizations are becoming more involved in promoting trainee financial wellness. Current literature reports residents have poor financial knowledge, high debt levels, low concern about their finances, and deficits in financial preparedness, but there has been little published on best practices for implementing financial wellness programs for residents or measuring meaningful outcomes of such programs. APPROACH: From June 2017 to 2019, the authors invited 277 internal medicine residents from the Stony Brook University Hospital, Montefiore Medical Center, and Johns Hopkins Bayview Medical Center residency programs to participate in financial wellness programs. Each institution held at least one 90-minute financial planning session; Stony Brook also had biannual financial wellness check-ins. Participants were invited to complete a presession, an immediate postsession, and a year-end survey to assess changes in financial planning behaviors. OUTCOMES: Survey response rates were 49% (135/277) for the presession survey, 47% (130/277) for the immediate postsession survey, and 22% (61/277) for the year-end survey. Ninety-six percent (125/130) found the sessions helpful and 98% (120/123) recommended continuing the program in the future. At year-end, the most frequent completed financial planning actions prompted by the session included saving emergency funds, creating a monthly budget, consolidating loans via the Public Service Loan Forgiveness program, contributing to retirement savings, and participating in an employer's retirement plan. Residents liked that some sessions were during intern orientation before the selection of retirement plans. Postgraduate year (PGY) 1 residents were more likely to complete positive financial planning actions and to agree or strongly agree that the session prompted them to take financial planning actions than PGY-2 and PGY-3 residents. NEXT STEPS: While financial wellness programs are well received by internal medicine residents, more robust evidence is needed on curricular delivery methods and program features that promote positive financial planning behaviors.


Asunto(s)
Administración Financiera , Internado y Residencia , Educación de Postgrado en Medicina , Promoción de la Salud , Humanos , Encuestas y Cuestionarios
19.
Sci Rep ; 11(1): 15795, 2021 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-34349183

RESUMEN

AgNPs are nanomaterials with many potential biomedical applications. In this study, the two novel yeast strains HX-YS and LPP-12Y capable of producing biological silver nanoparticles were isolated. Sequencing of ribosomal DNA-ITS fragments, as well as partial D1/D2 regions of 26S rDNA indicated that the strains are related to species from the genus Metschnikowia. The BioAgNPs produced by HX-YS and LPP-12Y at pH 5.0-6.0 and 26 °C ranged in size from 50 to 500 nm. The antibacterial activities of yeast BioAgNPs against five pathogenic bacteria were determined. The highest antibacterial effect was observed on P. aeruginosa, with additional obvious effects on E. coli ATCC8099 and S. aureus ATCC10231. Additionally, the BioAgNPs showed antiproliferative effects on lung cancer cell lines H1975 and A579, with low toxicity in Beas 2B normal lung cells. Therefore, the AgNPs biosynthesized by HX-YS and LPP-12Y may have potential applications in the treatment of bacterial infections and cancer.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Neoplasias Pulmonares/patología , Nanopartículas del Metal , Metschnikowia/metabolismo , Nanoestructuras , Pseudomonas aeruginosa/efectos de los fármacos , Compuestos de Plata/metabolismo , Compuestos de Plata/farmacología , Staphylococcus aureus/efectos de los fármacos , Línea Celular Tumoral , ADN Ribosómico , Humanos , Metschnikowia/genética , Metschnikowia/aislamiento & purificación
20.
Antiviral Res ; 193: 105141, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34274417

RESUMEN

Ebola virus (EBOV) of the genus Ebolavirus belongs to the family Filoviridae, which cause disease in both humans and non-human primates. Zaire Ebola virus accounts for the highest fatality rate, reaching 90%. Considering that EBOV has a high infection and fatality rate, the development of a highly effective vaccine has become a top public health priority. Glycoprotein (GP) plays a critical role during infection and protective immune responses. Herein, we developed an EBOV GP recombinant DNA vaccine that targets the major histocompatibility complex (MHC) class II compartment by fusing with lysosomal-associated membrane protein 1 (LAMP1). Through lysosome trafficking and antigen presentation transferring, the LAMP1 targeting strategy successfully improved both humoral and cellular EBOV-GP-specific immune responses. After three consecutive immunizations, the serum antibody titers, especially the neutralizing activity of mice immunized with the pVAX-LAMP/GPEBO vaccine were significantly higher than those of the other groups. Antigen-specific T cells showed positive activity against three dominant peptides, EAAVSHLTTLATIST, IGEWAFWETKKNLTR, and ELRTFSILNRKAIDF, with high affinity for MHC class II molecules predicted by IEDB-recommended. Preliminary safety observation denied histological alterations. DNA vaccine candidate pVAX-LAMP/GPEBO shows promise against Ebola epidemic and further evaluation is guaranteed.


Asunto(s)
Vacunas contra el Virus del Ébola/inmunología , Ebolavirus/inmunología , Glicoproteínas/inmunología , Vacunas de ADN/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Células 3T3 BALB , Vacunas contra el Virus del Ébola/administración & dosificación , Vacunas contra el Virus del Ébola/efectos adversos , Vacunas contra el Virus del Ébola/genética , Ebolavirus/genética , Femenino , Glicoproteínas/genética , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Proteínas de Membrana de los Lisosomas/genética , Proteínas de Membrana de los Lisosomas/inmunología , Ratones , Pruebas de Neutralización , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/efectos adversos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología
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