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Fucosyltransferase 2 (FUT2) gene, which regulates the formation of Histoblood group antigens, could determine the human susceptibility to norovirus. This study aimed to investigate the correlation between FUT2 gene polymorphism and susceptibility to norovirus gastroenteritis in Han Chinese population. A total of 212 children patients with acute gastroenteritis were enrolled. The stool and serum samples were collected respectively. We used the qPCR method to detect the norovirus infection status from the stool samples, and we used serum samples to detect the FUT2 polymorphism. A case-control study was conducted to investigate the three common SNPs polymorphisms (rs281377, rs1047781, and rs601338) of FUT2 gene with sanger sequencing method. The results indicated that the homozygous genotypes and mutant allele of rs1047781 (A385T) would downgrade the risk of norovirus gastroenteritis in Chinese Han population (AA vs. TT, odds ratio [OR] = 0.098, 95% confidence interval [CI] = 0.026-0.370, p = 0.001; AA + AT vs. TT, OR = 0.118. 95% CI = 0.033-0.424, p = 0.001; A vs. T, OR = 0.528, 95% CI = 0.351-0.974, p = 0.002). There were no significant difference of rs281377 (C357T) and rs601338 (G428A) polymorphisms between norovirus positive and norovirus negative groups (p > 0.05). The haplotype T-T-G was less susceptible (OR = 0.49, 95% CI = 0.31-0.79, p = 0.0034) to norovirus infection compared to other haplotypes. Our results investigated the relationship between the FUT2 gene polymorphisms and norovirus susceptibility in Han Chinese population, and firstly revealed that children with homozygous genotypes and mutant alleles of FUT2 rs1047781 (A385T) were less susceptible to norovirus gastroenteritis.
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Pueblo Asiatico , Infecciones por Caliciviridae , Fucosiltransferasas , Galactósido 2-alfa-L-Fucosiltransferasa , Gastroenteritis , Predisposición Genética a la Enfermedad , Genotipo , Norovirus , Polimorfismo de Nucleótido Simple , Humanos , Fucosiltransferasas/genética , Infecciones por Caliciviridae/genética , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/epidemiología , Femenino , Masculino , Gastroenteritis/virología , Gastroenteritis/genética , Estudios de Casos y Controles , Preescolar , Norovirus/genética , Pueblo Asiatico/genética , Lactante , China/epidemiología , Niño , Heces/virología , Alelos , Haplotipos , Pueblos del Este de AsiaRESUMEN
Light can influence many psychophysiological functions beyond vision, including alertness, circadian rhythm, and sleep, namely the non-image forming (NIF) effects of light. Melanopic equivalent daylight illuminance (mel-EDI) is currently recommended as the predictor of the NIF effects of light. Although light dose is also critical for entraining and regulating circadian cycle, it is still unknown whether relatively low mel-EDI light exposure for prolonged duration in the evening would affect pre-sleep arousal and subsequent sleep. In all, 18 healthy college students (10 females, mean [standard deviation] age 21.67 [2.03] years) underwent 2 experimental nights with a 1 week interval in a simulated bedroom environment. During experimental nights, participants were either exposed to high or low mel-EDI light (73 versus 38 lx mel-EDI, 90 versus 87 photopic lx at eye level, 150 photopic lx at table level) for 3.5 h before regular bedtime, and their sleep was monitored by polysomnography. Subjective sleepiness, mood, and resting-state electroencephalography during light exposure were also investigated. Results showed no significant differences in sleep structure and sleep quality between the two light conditions, whereas 3.5 h of exposure to high versus low mel-EDI light induced marginally higher physiological arousal in terms of a lower delta but higher beta power density before sleep, as well as a lower delta power density during sleep. Moreover, participants felt happier before sleep under exposure to high versus low mel-EDI light. These findings together with the current literature suggest that evening prolonged relatively low mel-EDI light exposure may mildly increase arousal before and during sleep but affected sleep structure less.
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Nivel de Alerta , Ritmo Circadiano , Electroencefalografía , Luz , Polisomnografía , Sueño , Humanos , Femenino , Nivel de Alerta/fisiología , Adulto Joven , Masculino , Sueño/fisiología , Ritmo Circadiano/fisiología , Afecto/fisiología , Adulto , Calidad del SueñoRESUMEN
In this study, we explored a concise and mild synthetic route to produce novel C-14 arylcarbamate derivatives of andrographolide, a known anti-inflammatory and anticancer natural product. Upon assessing their anti-cancer efficacy against pancreatic ductal adenocarcinoma (PDAC) cells, some derivatives showed stronger cytotoxicity against PANC-1 cells than andrographolide. In addition, we demonstrated one derivative, compound 3m, effectively reduced the expression of oncogenic p53 mutant proteins (p53R273H and p53R248W), proliferation, and migration in PDAC lines, PANC-1 and MIA PaCa-2. Accordingly, the novel derivative holds promise as an anti-cancer agent against pancreatic cancer. In summary, our study broadens the derivative library of andrographolide and develops an arylcarbamate derivative of andrographolide with promising anticancer activity against PDAC.
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Carcinoma Ductal Pancreático , Diterpenos , Neoplasias Pancreáticas , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Diterpenos/farmacología , Línea Celular TumoralRESUMEN
Needle electromyogram (EMG) research has suggested that endplate noise (EPN) is a characteristic of myofascial trigger points (MTrPs). Although several studies have observed MTrPs through ultrasonography, whether they are hyperechoic or hypoechoic in ultrasound images is still controversial. Therefore, this study determined the echogenicity of MTrP ultrasonography. In stage 1, the MTrP of rat masseter muscle was identified through palpation and marked. Needle EMG was performed to detect the presence of EPN. When EPN was detected, ultrasound scans and indwelling needles were used to identify the nodule with a different grayscale relative to that of its surrounding tissue, and the echogenicity of the identified MTrP was determined. In stage 2, these steps were reversed. An ultrasound scan was performed to detect the nodule at the marked site, and an EMG needle was inserted into the nodule to detect EPN. There were 178 recordings in each stage, obtained from 45 rats. The stage 1 results indicate that the MTrPs in ultrasound images were hypoechoic with a 100% sensitivity of assessment. In stage 2, the accuracy and precision of MTrP detection through ultrasonography were 89.9% and 89.2%, respectively. The results indicate that ultrasonography produces highly accurate and precise MTrP detection results.
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Síndromes del Dolor Miofascial , Puntos Disparadores , Ratas , Animales , Síndromes del Dolor Miofascial/diagnóstico por imagen , Ultrasonografía , Electromiografía , AgujasRESUMEN
BACKGROUND & AIMS: Pancreatic cancer (PC) is the third leading cause of cancer-related death with a 5-year survival rate of approximately 10%. It typically presents as a late-stage incurable cancer and chemotherapy provides modest benefit. Here, we demonstrate the feasibility, safety, and potency of a novel human natural killer (NK) cell-based immunotherapy to treat PC. METHODS: The expression of prostate stem cell antigen (PSCA) was evaluated in primary PC at messenger RNA and protein levels. The processes of retroviral transduction, expansion, activation, and cryopreservation of primary human NK cells obtained from umbilical cord blood were optimized, allowing us to develop frozen, off-the-shelf, allogeneic PSCA chimeric antigen receptor (CAR) NK cells. The safety and efficacy of PSCA CAR NK cells also expressing soluble (s) interleukin 15 (PSCA CAR_s15 NK cells) were evaluated in vitro and in vivo. RESULTS: PSCA was elevated in primary human PC compared with the adjacent or other normal tissues. PSCA CAR_s15 NK cells displayed significant tumor-suppressive effects against PSCA(+) PC in vitro before and after 1 cycle of freeze-thaw. The viability of frozen PSCA CAR_s15 NK cells persisted more than 90 days in vivo after their last infusion and significantly prolonged the survival of mice engrafted with human PC. CONCLUSIONS: PSCA CAR_s15 NK cells showed therapeutic efficacy in human metastatic PC models without signs of systematic toxicity, providing a strong rationale to support clinical development.
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Neoplasias Pancreáticas , Receptores Quiméricos de Antígenos , Animales , Línea Celular Tumoral , Citotoxicidad Inmunológica , Humanos , Inmunoterapia Adoptiva , Células Asesinas Naturales , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Neoplasias Pancreáticas/patología , Próstata , Células Madre/metabolismo , Neoplasias PancreáticasRESUMEN
BACKGROUND: Genomic imprinting refers to a subset of genes that are expressed from only one parental allele during seed development in plants. Studies on genomic imprinting have revealed that intraspecific variations in genomic imprinting expression exist in naturally genetic varieties. However, there have been few studies on the functional analysis of allele-specific imprinted genes. RESULTS: Here, we generated three reciprocal crosses among the B73, Mo17 and CAU5 inbred lines. Based on the transcriptome-wide analysis of allele-specific expression using RNA sequencing technology, 305 allele-specific imprinting genes (ASIGs) were identified in embryos, and 655 ASIGs were identified in endosperms from three maize F1 hybrids. Of these ASIGs, most did not show consistent maternal or paternal bias between the same tissue from different hybrids or different tissues from one hybrid cross. By gene ontology (GO) analysis, five and eight categories of GO exhibited significantly higher functional enrichments for ASIGs identified in embryo and endosperm, respectively. These functional categories indicated that ASIGs are involved in intercellular nutrient transport, signaling pathways, and transcriptional regulation of kernel development. Finally, the mutation and overexpression of one ASIG (Zm305) affected the length and width of the kernel. CONCLUSION: In this study, our data will be helpful in gaining further knowledge of genes exhibiting allele-specific imprinting patterns in seeds. The gain- and loss-of-function phenotypes of ASIGs associated with agronomically important seed traits provide compelling evidence for ASIGs as crucial targets to optimize seed traits in crop plants.
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Endospermo , Transcriptoma , Endospermo/metabolismo , Alelos , Zea mays/metabolismo , Semillas/genética , Impresión Genómica , Regulación de la Expresión Génica de las PlantasRESUMEN
Glioblastoma (GBM) is a highly aggressive cancer that currently lacks effective treatments. Pyroptosis has emerged as a promising therapeutic approach for cancer, but there is still a need for new pyroptosis boosters to target cancer cells. In this study, it is reported that Aloe-emodin (AE), a natural compound derived from plants, can inhibit GBM cells by inducing pyroptosis, making it a potential booster for pyroptosis-mediated GBM therapy. However, administering AE is challenging due to the blood-brain barrier (BBB) and its non-selectivity. To overcome this obstacle, AE@ZIF-8 NPs are developed, a biomineralized nanocarrier that releases AE in response to the tumor's acidic microenvironment (TAM). Further modification of the nanocarrier with transferrin (Tf) and polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) improves its penetration through the BBB and tumor targeting, respectively. The results show that AE-NPs (Tf-PEG-PLGA modified AE@ZIF-8 NPs) significantly increase the intracranial distribution and tumor tissue accumulation, enhancing GBM pyroptosis. Additionally, AE-NPs activate antitumor immunity and reduce AE-related toxicity. Overall, this study provides a new approach for GBM therapy and offers a nanocarrier that is capable of penetrating the BBB, targeting tumors, and attenuating toxicity.
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Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Glioblastoma/patología , Piroptosis , Línea Celular Tumoral , Transferrina , Neoplasias Encefálicas/tratamiento farmacológico , Microambiente TumoralRESUMEN
Efficient quantification of the affinity of a drug and the targeted protein is critical for strategic drug design. Among the various molecules, turn-on fluorescent probes are the most promising signal transducers to reveal the binding strength and site-specificity of designed drugs. However, the conventional method of measuring the binding ability of turn-on fluorescent probes by using the fractional occupancy under the law of mass action is time-consuming and a massive sample is required. Here, we report a new method, called dual-concentration ratio method, for quantifying the binding affinity of fluorescent probes and human serum albumin (HSA). Temperature-dependent fluorescence intensity ratios of a one-to-one complex (L â HSA) for a turn-on fluorescent probe (L), e. g., ThT (thioflavin T) or DG (dansylglycine), with HSA at two different values of [L]0 /[HSA]0 under the constraint [HSA]0 >[L]0 were collected. The van't Hoff analysis on these association constants further resulted in the thermodynamic properties. Since only two samples at different [L]0 /[HSA]0 are required without the need of [L]0 /[HSA]0 at a wide range, the dual-concentration ratio method is an easy way to greatly reduce the amounts of fluorescent probes and proteins, as well as the acquisition time.
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Colorantes Fluorescentes , Albúmina Sérica Humana , Humanos , Albúmina Sérica Humana/metabolismo , Albúmina Sérica/química , Sitios de Unión , Unión Proteica , Termodinámica , Espectrometría de FluorescenciaRESUMEN
Light-based technologies of different wavelengths can inactivate pathogenic microorganisms, but each wavelength has its limitations. This work explores the potential of sequential treatments with different wavelengths for enhancing the disinfection performance of individual treatments by employing various bactericidal mechanisms. The effectiveness, inactivation kinetics, and bactericidal mechanisms of treatments with 222/405, 280/405, and 405 nm alone against Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium, and Pseudomonas aeruginosa were evaluated. Inactivation experiments were performed in thin liquid bacterial suspensions that were treated either individually with 48 h of 405-nm light or sequentially with (i) 30 s of 222-nm far-UV-C light, followed by 48 h of 405-nm light, or (ii) 30 s of 280-nm far-UV-C light, followed by 48 h of 405-nm light. Survivors were recovered and enumerated by standard plate counting. All inactivation curves were non-linear and followed the Weibull model (0.99 ≥ R2 ≥ 0.70). Synergistic effects were found for E. coli, L. monocytogenes, and S. Typhimurium, with maximum inactivation level increases of 2.9, 3.3, and 1.1 log CFU after the sequential treatments, respectively. Marginal synergy was found for S. aureus, and an antagonistic effect was found for P. aeruginosa after sequential treatments. Significant differences in reactive oxygen species accumulation were found (P < 0.05) after various treatment combinations, and the performance of sequential treatments was correlated with cellular oxidative damage. The sequential wavelength treatments proposed demonstrate the potential for enhanced disinfection of multiple foodborne pathogens compared with individual wavelength treatments, which can have significant food safety benefits. IMPORTANCE Nonthermal light-based technologies offer a chemical-free method to mitigate microbial contamination in the food and healthcare industries. However, each individual wavelength has different limitations in terms of efficacy and operating conditions, which limits their practical applicability. In this study, bactericidal synergism of sequential treatments with different wavelengths was identified. Pre-treatments with 280 and 222 nm enhanced the disinfection performance of follow-up 405-nm treatments for multiple foodborne pathogens by inducing higher levels of cellular membrane damage and oxidative stress. These findings deliver useful information for light equipment manufacturers, food processors, and healthcare users, who can design and optimize effective light-based systems to realize the full potential of germicidal light technologies. The results from the sequential treatments offer practical solutions to improve the germicidal efficacy of visible light systems, as well as provide inspiration for future hurdle disinfection systems design, with a positive impact on food safety and public health.
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Escherichia coli O157 , Listeria monocytogenes , Staphylococcus aureus , Rayos Ultravioleta , Luz , Desinfección/métodos , Microbiología de Alimentos , Recuento de Colonia MicrobianaRESUMEN
Peanut meal (PM) is a by-product of extracting oil from peanut kernels. Although peanut meal contains protein, carbohydrates, minerals, vitamins, and small amounts of polyphenols and fiber, it has long been used as a feed in the poultry and livestock industries due to its coarse texture and unpleasant taste. It is less commonly utilized in the food processing industry. In recent years, there has been an increasing amount of research conducted on the deep processing of by-products from oil crops, resulting in the high-value processing and utilization of by-products from various oil crops. These include peanut meal, which undergoes treatments such as enzymatic hydrolysis in industries like food, chemical, and aquaculture. The proteins, lipids, polyphenols, fibers, and other components present in these by-products and hydrolysates can be incorporated into products for further utilization. This review focuses on the research progress in various fields, such as the food processing, breeding, and industrial fields, regarding the high-value utilization of peanut meal and its hydrolysates. The aim is to provide valuable insights and strategies for maximizing the utilization of peanut meal resources.
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Arachis , Fitomejoramiento , Manipulación de Alimentos , Hidrolisados de Proteína , Industria de Procesamiento de Alimentos , PolifenolesRESUMEN
Di(2-ethylhexyl) phthalate (DEHP) with continuous high concentration was used as the sole carbon and energy source to isolate a new bacterial consortium (K1) from agricultural soil covered with plastic film for a long time. Unclassified Comamonadaceae, Achromobacter, and Pseudomonas in K1 were identified as major genera of the consortium by high-throughput sequencing, and unclassified Commanadaceae was first reported to be related to DEHP degradation. Response surface method (RSM) showed that the optimum conditions for K1 to degrade DEHP were 31.4 °C, pH 7.3, and a concentration of 420 mg L-1. K1 maintains normal cell viability and stable DEHP degradation efficiency in the range of 10-3000 mg L-1 DEHP concentration, which is superior to existing research. The biodegradation of DEHP followed first-order kinetics when the initial concentration of DEHP was between 100 and 3,000 mg L-1. GC-MS analysis of different treatment groups showed that DEHP was degraded by the consortium group through the de-esterification pathway, and treatment effect was significantly better than that of the single bacteria treatment group. The subsequent substrate utilization experiment further confirmed that K1 could quickly mineralize DEHP. In addition, K1 has high degradation capacity for the most common phthalate acid esters in the environment.
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Dietilhexil Ftalato , Ácidos Ftálicos , Dietilhexil Ftalato/análisis , Dietilhexil Ftalato/metabolismo , Biodegradación Ambiental , Bacterias/genética , Bacterias/metabolismoRESUMEN
The present study conducted the concentration evaluation, pollution assessment, source analysis, and risk assessment of heavy metals in the soil of the CPUA, China, to contribute to the smooth construction of urban agglomeration. Elevated levels of mean concentrations of cadmium (Cd), chromium (Cr), and copper (Cu) in the soils were shown compared to background values. Cu and zinc (Zn) and also lead (Pb) and Cd exhibited spatial similarity. Manganese (Mn) and Cr exhibited point source characteristics such as the concentrations at a point much higher than the surrounding area. The potential ecological risk in the northern region belonged to the moderate risk level category. Cd contributed over 90% to the potential ecological risk. The health risk among children was higher than that among adults. The major exposure pathways were different for adults and children. Exposure, as shown using Hazard Index (HI), to adults was mainly through the skin contact route, while to children was through both the skin contact and ingestion route. The primary CR (carcinogenic risk) to adults was through the inhalation route, while that to children was through the ingestion route. In both children and adults, Cr was the main contributor to HI and CR. According to the Monte Carlo simulation results, the cumulative probability of exceeding the critical value of HI for children was approximately 2.8-3.0 times that for adults. According to the sensitivity analysis results, non-carcinogenic risk prevention should begin mainly by reducing exposure duration and skin contact. The cancer risk may be reduced primarily by decreasing the exposure duration and controlling ingestion. The PMF (Positive Matrix Factorization) source analysis revealed that Pb mainly came from transportation sources. In addition, Cu, Pb, and Mn were derived mainly from agricultural sources. Cr was derived mostly from a natural source, and Cd originated mainly from an industrial source.
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Metales Pesados , Contaminantes del Suelo , Adulto , Niño , Humanos , Suelo , Cadmio/análisis , Monitoreo del Ambiente/métodos , Plomo/análisis , Método de Montecarlo , Contaminantes del Suelo/análisis , Metales Pesados/toxicidad , Metales Pesados/análisis , Cromo/análisis , Medición de Riesgo , Manganeso/análisis , ChinaRESUMEN
The poor adhesion performance of typical gels still remains a challenge to find a simple method to achieve strong and reversible adhesion with the existence of water. Here, a poly(acryloyloxyethyl trimethyl ammonium chloride-co-2-vinyl-4-6-diamino-1,3,5-triazine) (P(DAC-co-VDT)) gel with high and adjustable interfacial adhesion is fabricated by combining cation-triazine π interaction and multiple hydrogen bonding and through a one-pot route. Characterization of the gels reveals that the two types of interactions are introduced into the gel network and that the gel-gel and gel-glass interfacial adhesion can be readily adjusted in a wide range from 15.98 to 123.60 kPa. This approach enables the creation of high-strength composites using P(DAC-co-VDT) gel as matrix, anionic monomer sodium p-styrene sulfonate as ion concentration adjustor, and discrete quartz sands as filler with easy and repeated moldability and self-healing capability.
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Triazinas , Enlace de Hidrógeno , Polielectrolitos , Geles/química , CationesRESUMEN
To investigate the variations in environmental behavior (levels, distribution, sources, and soil toxicity) of polycyclic aromatic hydrocarbons (PAHs) under the impact of anthropogenic activities during the urbanization process, we collected soil samples from 195 sites in the Central Plains Urban Agglomeration (CPUA), North China, and analyzed 16 U.S. Environmental Protection Agency (EPA) PAH priority pollutants. We divided the sampling sites into three groups (urban area, industrial area, and farmland) and collected soil samples (0-20 cm surface layer). ∑16PAHs concentrations in the soils of the urban area, industrial area, and farmland ranged from 24.2 to 4400 ng/g, 12.3-8780 ng/g, and 20.9-852 ng/g (the average value of 349, 634, and 186 ng/g), respectively. The 4 to 5 ring PAHs were dominant compounds in three soil types, accounting for 65-80% of the ∑16PAHs. The results of the source analysis showed that the PAHs in the soils of CPUA were mainly from energy consumption. PAH levels in urban and industrial soils had a potential low cancer risk. The impact of urbanization on PAHs in the soil was bidirectional. On the one hand, the level of PAHs in the farmland soil might increase due to burning coal and agricultural machinery, which releases diesel or petrol fumes. On the other hand, in the urbanization process, the PAH content in urban soil and industrial soil showed a downward trend due to the implementation of environmental protection policies in China, which have reduced the atmospheric input of PAHs into the soil.
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Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Efectos Antropogénicos , China , Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis , UrbanizaciónRESUMEN
Preeclampsia is one of the most serious pregnancy complications. It may be caused by immunological changes in the early placental microenvironment. The contents of small EVs may serve as biomarkers of pregnancy complications. Evidence suggests that the balance between T helper 17 (Th17) and regulatory T (Treg) cells are critical for preventing preeclampsia. The study recruited 39 pregnant women with preeclampsia and 127 healthy pregnant women. We assessed the levels of both Th17 and Treg cytokines (IL-10, IL-17, IL-21, IL-22, and TGF-ß) in their plasma and small EVs. We found significant differences in the levels of all cytokines in the plasma between the two groups during the second trimester. We also observed significant differences between the two groups in the levels of EV-encapsulated cytokines IL-21, IL-22, and TGF-ß, as well as in total small EVs, during the second trimester. The ROC analysis showed that the classification efficiency (AUC) of TGF-ß in small EVs was 0.81. TGF-ß had the best discriminant ability of all the single EV biomarkers tested, the cross-validation of the accuracy was 0.89. Th17 and Treg cytokines in plasma and small EVs may contribute to maternal immune activation and clarify the potential mechanisms of small EVs and cytokines in preeclampsia.
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Vesículas Extracelulares , Preeclampsia , Biomarcadores , Citocinas , Femenino , Humanos , Interleucina-10 , Interleucina-17 , Placenta , Preeclampsia/diagnóstico , Embarazo , Linfocitos T Reguladores , Células Th17 , Factor de Crecimiento Transformador betaRESUMEN
PURPOSE: To explore the therapeutic effects of Bu-Shen-Ning-Xin decoction (BSNXD) on POI and the underlying mechanism. METHODS: VCD was used to induce the in vivo and in vitro POI model. HE staining was used to evaluate the pathological state of ovarian tissues. ELISA was used to detect the production of hormones in the serum and granule cells (GCs). An immunohistochemical assay was used to determine the expression of ATG7 and p-AKT in the ovarian tissues. The number of oocytes in POI rats was counted. The mitochondrial membrane potential (MMP) in oocytes and GCs was detected by flow cytometry. A Western blot assay was used to measure the expression of AKT, p-AKT, p-mTOR, mTOR, S6K, p-S6K, ULK1, p-ULK1, Beclin-1, Bcl-2, LC3-II, LC3-I, ATG7, and cleaved Caspase3. The numbers of autophagosomes were detected by transmission electron microscope and autophagic flux assay. The CCK-8 assay was used to detect the cell viability. RESULTS: Decreased primary follicles in the ovarian tissues, elevated concentration of FSH, and LH, suppressed concentration of E2 and AMH in the serum, reduced number of oocytes, and mitochondrial dysfunction in oocytes induced by VCD were significantly reversed by BSNXD. Activated autophagy state and inhibited PI3K/AKT/mTOR pathway stimulated by VCD in both ovarian tissues and GCs were dramatically reversed by BSNXD. The protective effect of BSNXD on VCD-treated GCs was abolished by LY294002, an inhibitor of the PI3K/AKT/mTOR pathway. CONCLUSION: Our data revealed that BSNXD alleviated POI by regulating autophagy of granule cells through activating PI3K/AKT/mTOR pathway.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Animales , Apoptosis , Autofagia , Beclina-1/farmacología , Medicamentos Herbarios Chinos , Femenino , Hormona Folículo Estimulante/uso terapéutico , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Insuficiencia Ovárica Primaria/inducido químicamente , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Cefotetan is widely used to treat bacterial infections in the clinic owing to its broad spectrum of antibacterial activity. In the present study, we demonstrate that cefotetan can bind to the conserved ligand-binding pocket of human Raf1 kinase inhibitory protein (hRKIP), which acts as a negative regulator of the Ras/Raf1/MEK/ERK signaling pathway. The cefotetan-bound hRKIP adopts a rigid structure with insufficient space for binding Raf1 kinase, thereby reliving the inhibitory activity of hRKIP in the Ras/Raf1/MEK/ERK signaling pathway and enhancing the phosphorylation level of ERK. Both NMR titration and molecular docking approaches show that several residues (P74, Y81, W84, P111, P112, K113, S142, G143, D144, W173, P178, Y181 and L184) play crucial roles in hRKIP binding cefotetan. NMR dynamics analysis reveals that the binding of cefotetan with hRKIP promotes ps-ns internal motion but reduces µs-ms conformational exchange for residues in the cefotetan-binding pocket of hRKIP. Our results not only disclose the structural basis of cefotetan upregulating the Ras/Raf1/MEK/ERK signaling pathway but also benefit developing novel drugs against diseases caused by the impaired Ras/Raf1/MEK/ERK pathway.
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Cefotetán , Sistema de Señalización de MAP Quinasas , Humanos , Simulación del Acoplamiento Molecular , Transducción de Señal , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: To better understand biomechanical factors that affect intervertebral alignment throughout active therapeutic exercise, it is necessary to determine spinal kinematics when subjects perform spinal exercises. This study aims to investigate the outcomes of active cervical therapeutic exercise on intervertebral foramen changes in neck pain patients with disc herniation. METHODS: Thirty diagnosed C4/5 and/or C5/6 disc-herniated patients receiving an 8-week cervical therapeutic exercise program were followed up with videofluoroscopic images. The dynamic changes in the foramen were computed at different timepoints, including the neutral position, end-range positions in cervical flexion-extension, protrusion-retraction, and lateral flexion movements. RESULTS: The results showed that the active cervical flexion, retraction, and lateral flexion away from the affected side movements increased the area of the patients' intervertebral foramen; while the active extension, protrusion, and lateral flexion toward the affected side reduced the areas of intervertebral foramen before treatment. After the treatment, the active cervical flexion significantly increased the C2/3, C3/4, and C6/7 foramen area by 5.02-8.67% (p = 0.001 ~ 0.029), and the extension exercise significantly reduced the C2/3 and C4/5 area by 5.12-9.18% (p = 0.001 ~ 0.006) compared to the baseline. Active retraction movement significantly increased the foramen area from C2/3 to C6/7 by 3.82-8.66% (p = 0.002 ~ 0.036 with exception of C5/6). Active lateral flexion away from the affected side significantly increased the foramen by 3.71-6.78% (p = 0.007 ~ 0.046 with exception of C6/7). CONCLUSIONS: The 8-week therapeutic exercises including repeated cervical retraction, extension, and lateral flexion movements to the lesion led to significant changes and improvements in intervertebral foramen areas of the patients with disc herniation. TRIAL REGISTRATION: ISRCTN61539024.
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Desplazamiento del Disco Intervertebral , Disco Intervertebral , Fenómenos Biomecánicos , Vértebras Cervicales/diagnóstico por imagen , Terapia por Ejercicio , Humanos , Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/terapia , Cuello , Dolor de Cuello/diagnóstico por imagen , Dolor de Cuello/etiología , Dolor de Cuello/terapia , Rango del Movimiento ArticularRESUMEN
To improve the removal efficiency of antibiotics in moving bed biofilm reactor, suspended biochar block was prepared by the one-pot process and was used as carriers to construct a reaction device to study the treatment effect of antibiotic wastewater. The characteristics of the hanging biofilm in wastewater were investigated. And the mechanism of biochar as a biological carrier has been studied. The results showed that in the 45-day experiment, the maximum number of biofilms for suspended biochar carriers was twice 3.4 times that of the high-density polyethylene carriers. When 10 mg/L tetracycline was added to the reactor, the removal efficiency of the tetracycline removal rate was 71.85% and the chemical oxygen demand (COD), total nitrogen (TN), and NH4+-N removal efficiency reached to 89.95, 61.91 and 85.47% respectively. Suspension biochar carriers can reduce fluctuations in redox potentials, thereby improving the cellular efficiency of microorganisms. Meanwhile, it inhibits the production of soluble microbial products and extracellular polymers, reduces toxic effects, and enhances the adhesion between microorganisms and carriers. The microbial communities of the two carriers were investigated by high-throughput sequencing techniques. Suspended biochar significantly increased the relative abundance of Hydrogenophaga and Comamonas, and improved the ability of nitrification and denitrification. Comamonas could be responsible for tetracycline degradation.
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Compuestos Heterocíclicos , Aguas Residuales , Antibacterianos , Biopelículas , Reactores Biológicos , Carbón Orgánico , Desnitrificación , Nitrificación , Nitrógeno/química , Polietileno , Tetraciclina , Eliminación de Residuos Líquidos/métodosRESUMEN
OBJECTIVE: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined. DESIGN: We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs. RESULTS: MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09). CONCLUSIONS: Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.