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In mammals, CD4 is found to be expressed on T cells and innate immune cells, however, teleost cells bearing CD4 have not been well identified and characterized. In this study, we identified two different CD4-1+ cell subsets in grass carp (Ctenopharyngodon idella): CD4-1+ lymphocytes (Lym) and CD4-1+ myeloid cells (Mye), both of which had the highest proportions in the head kidney. The mRNA expression analysis showed that CD4-1, CD4-2, TCRß, CD3γ/δ, and LCK1 are highly expressed in CD4-1+ Lym and also expressed in CD4-1+ Mye. Furthermore, we found that CD4-1+ Lym have a Lym morphology and highly express T-cell cytokines, suggesting that they are CD4+ T cells equivalent to mammalian Th cells. On the other hand, CD4-1+ Mye were found to have a morphology of macrophage and highly express macrophage marker gene MCSFR, indicating that they are macrophages. In addition, functional analysis revealed that CD4-1+ Mye possess phagocytic ability and great antigen-processing ability. Taken together, our study sheds further light on the composition and function of CD4+ cells in teleost fish.
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Carpas , Proteínas de Peces , Animales , Carpas/inmunología , Carpas/genética , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígenos CD4/genética , Antígenos CD4/inmunología , Antígenos CD4/metabolismo , Riñón Cefálico/inmunología , Riñón Cefálico/citología , Células Mieloides/inmunología , Inmunidad Innata/genéticaRESUMEN
Silica nanoparticles (SiNPs) are widely used in the biomedical field and can enter the central nervous system through the blood-brain barrier, causing damage to hippocampal neurons. However, the specific mechanism remains unclear. In this experiment, HT22 cells were selected as the experimental model in vitro, and the survival rate of cells under the action of SiNPs was detected by MTT method, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and adenosine triphosphate (ATP) were tested by the kit, the ultrastructure of the cells was observed by transmission electron microscope, membrane potential (MMP), calcium ion (Ca2+) and apoptosis rate were measured by flow cytometry, and the expressions of mitochondrial functional protein, mitochondrial dynein, mitochondrial autophagy protein as well as apoptosis related protein were detected by Western blot. The results showed that cell survival rate, SOD, CAT, GSH-Px, ATP and MMP gradually decreased with the increase of SiNPs concentration, while intracellular ROS, Ca2+, LDH and apoptosis rate increased with the increase of SiNPs concentration. In total cellular proteins,the expressions of mitochondrial functional proteins VDAC and UCP2 gradually increased, the expression of mitochondrial dynamic related protein DRP1 increased while the expressions of OPA1 and Mfn2 decreased. The expressions of mitophagy related proteins PINK1, Parkin and LC3â ¡/LC3â increased and P62 gradually decreased, as well as the expressions of apoptosis related proteins Apaf-1, Cleaved-Caspase-3, Caspase-3, Caspase-9, Bax and Cyt-C. In mitochondrial proteins, the expressions of mitochondrial dynamic related proteins DRP1 and p-DRP1 were increased, while the expressions of OPA1 and Mfn2 were decreased. Expressions of mitochondrial autophagy associated proteins PINK1, Parkin, LC3II/LC3I increased, P62 decreased gradually, as well as the expressions of apoptosis related proteins Cleaved-Caspase-3, Caspase-3, and Caspase-9 increased, and Cyt-C expressions decreased. To further demonstrate the role of ROS and DRP1 in HT22 cell apoptosis induced by SiNPs, we selected the ROS inhibitor N-Acetylcysteine (NAC) and Dynamin-related protein 1 (DRP1) inhibitor Mdivi-1. The experimental results indicated that the above effects were remarkably improved after the use of inhibitors, further confirming that SiNPs induce the production of ROS in cells, activate DRP1, cause excessive mitochondrial division, induce mitophagy, destroy mitochondrial function and eventually lead to apoptosis.
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Dinaminas , Mitofagia , Nanopartículas , Dióxido de Silicio , Adenosina Trifosfato , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Dinaminas/metabolismo , Nanopartículas/toxicidad , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/farmacología , Superóxido Dismutasa/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Ratones , Línea Celular TumoralRESUMEN
Nuclear receptor binding SET domain protein 3 (NSD3) has recently been recognized as a new epigenetic target in the fight against cancer. NSD3, which is amplified, overexpressed or mutated in a variety of tumors, promotes tumor development by regulating the cell cycle, apoptosis, DNA repair and EMT. Therefore, the inhibition, silencing or knockdown of NSD3 are highly promising antitumor strategies. This paper summarizes the structure and biological functions of NSD3 with an emphasis on its carcinogenic or cancer-promoting activity. The development of NSD3-specific inhibitors or degraders is also discussed and reviewed in this paper.
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Lisina , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
Last several years, a rapid increase in drug resistance to traditional antibiotics has driven the emergence and development of antimicrobial peptides (AMPs). AMPs have also gained considerable attention from scientists due to their high potency in combatting infectious pathogens. A subset of analogues and their derivatives with specific targets have been successfully designed based on natural peptide patterns. In this review, scientific knowledge on the mechanisms of action related to biological activity and structure-activity relationship (SAR) of AMPs are summarized, and the biological applications in several important fields are critically discussed. SAR shows that the positive charge, secondary structure, special amino acid residues, hydrophobicity, and helicity of AMPs are closely related to their biological activities. The combination of nanotechnology, bioinformatics, and genetic engineering can accelerate to achieve the application of AMPs as effective, safe, economical, and nonresistant antimicrobial agents in medicine, the food and feed industries, and agriculture in coming years. Given the intense interest in AMPs, further investigations are needed in the future to evaluate the specific structure and function that make their use favorable in several industries. This review may provide a comprehensive reference for future studies on chemical modifications, mechanistic exploration, and applications of AMPs.
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Antiinfecciosos , Péptidos Antimicrobianos , Péptidos Catiónicos Antimicrobianos/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/farmacología , Relación Estructura-ActividadRESUMEN
Prunus mume Sieb. Et Zucc (P. mume) is an acidic fruit native to China (named Chinese Mei or greengage plum). It is currently cultivated in several Asian countries, including Japan ("Ume"), Korea (Maesil), and Vietnam (Mai or Mo). Due to its myriad nutritional and functional properties, it is accepted in different countries, and its characteristics account for its commercialization. In this review, we summarize the information on the bioactive compounds from the fruit of P. mume and their structure-activity relationships (SAR); the pulp has the highest enrichment of bioactive chemicals. The nutritional properties of P. mume and the numerous uses of its by-products make it a potential functional food. P. mume extracts exhibit antioxidant, anticancer, antimicrobial, and anti-hyperuricaemic properties, cardiovascular protective effects, and hormone regulatory properties in various in vitro and in vivo assays. SAR shows that the water solubility, molecular weight, and chemical conformation of P. mume extracts are closely related to their biological activity. However, further studies are needed to evaluate the fruit's potential nutritional and functional therapeutic mechanisms. The industrial process of large-scale production of P. mume and its extracts as functional foods or nutraceuticals needs to be further optimized.
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Prunus , Prunus/química , Frutas/química , Extractos Vegetales/farmacología , Extractos Vegetales/análisis , Relación Estructura-Actividad , Suplementos DietéticosRESUMEN
Immunoglobulins (Igs) are important effector molecules that mediate humoral immunity. A typical Ig consists of two heavy and two light chains. In teleosts, three Ig heavy chain isotypes (Igµ, Igδ and Igτ) and three Ig light chain isotypes (Igκ, Igλ and Igσ) have been identified. Compared to the heavy chains, teleost Ig light chains have been poorly studied due to the lack of antibodies. In this study, a mouse anti-Nile tilapia Igλ monoclonal antibody (mAb) was prepared, which could specifically recognize Igλ in serum and Igλ+ B cells in tissues. Further, the composition of IgM+ and Igλ+ B cell subsets was analyzed using this antibody and a mouse anti-tilapia IgM heavy chain mAb. The ratio of IgM+Igλ+ B cells to total IgM+ B cells in head kidney and peripheral blood was about 30%, while that in spleen was about 50%; the ratio of IgM-Igλ+ B cells to total Igλ+ B cells in head kidney and peripheral blood was about 45%, while that in spleen was about 25%. The IgM-Igλ+ B cells was speculated to be IgT+ B cells. Finally, we detected an increase in the level of specific antibodies against the surface antigen-Sip of Streptococcus agalactiae in serum after S. agalactiae infection, indicating that mouse anti-tilapia Igλ mAb can be used to detect the antibody level after immunization of Nile tilapia, which lays a foundation for the evaluation of immunization effect of tilapia vaccine.
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Subgrupos de Linfocitos B , Cíclidos , Enfermedades de los Peces , Infecciones Estreptocócicas , Tilapia , Ratones , Animales , Anticuerpos Monoclonales , Inmunidad Humoral , Inmunosupresores , Streptococcus agalactiae , Inmunoglobulina MRESUMEN
The study aimed to explore the role and mechanism of unfolded protein response (UPR) in methylmercury (MeHg)-induced Mouse Spermatocytes (GC-2spd[ts]) apoptosis. Methods such as MTT, flow cytometry, and Western Blot were used to evaluate the cell viability, membrane potential (MMP), reactive oxygen species (ROS), calcium ion (Ca2+ ), rate of cell apoptosis, and the expression of apoptosis-related and UPR-related protein. The results showed that with the increase of MeHg concentration, cell viability and MMP decreased, ROS, Ca2+ , rate of cell apoptosis, and the expression of apoptosis-related protein and UPR-related protein increased. To further explore the effect of ROS-induced oxidative damage on it, the ROS inhibitor N-acetyl-L-cysteine (NAC) was used. The effects of MeHg on germ cell (GC-2) cells were partially inhibited after NAC pretreatment. Our present study proved that MeHg might induce cell apoptosis by activating the UPR signaling pathway in GC-2 cells and affect normal reproductive function.
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Compuestos de Metilmercurio , Espermatocitos , Masculino , Ratones , Animales , Especies Reactivas de Oxígeno/metabolismo , Espermatocitos/metabolismo , Compuestos de Metilmercurio/toxicidad , Estrés Oxidativo , Apoptosis , Respuesta de Proteína Desplegada , Transducción de SeñalRESUMEN
Nuclear receptor binding SET Domain Protein 1 (NSD1) is a bifunctional transcriptional regulatory protein that encodes histone methyltransferase. Mono- and di-methylation of H3K36 by NSD1 is mainly primarily involved in the regulation of gene expression, DNA repair, alternative splicing, and other important biological processes. Many types of cancers, including acute myelogenous leukemia (AML), liver cancer, lung cancer, endometrial carcinoma, colorectal cancer, and pancreatic cancer, are associated with NSD1 fusion, missense mutation, nonsense mutation, silent mutation, deletion, and insertion of frameshift, and deletion in a frame. Therefore, targeting NSD1 may be a potential strategy for tumor therapy. An in-depth study of the structure and biological activities of NSD1 sets the groundwork for improving tumor therapy and creating NSD1 inhibitors. This article emphasizes the role of NSD1 in tumorigenesis and the development of NSD1 targeted small-molecule inhibitors.
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N-Metiltransferasa de Histona-Lisina/metabolismo , Neoplasias/metabolismo , Animales , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , N-Metiltransferasa de Histona-Lisina/química , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genéticaRESUMEN
OBJECTIVE: Clostridioides difficile may colonize healthy infants and young children asymptomatically and for the long-term. C. difficile genotypes and the rate and determinants of colonization differ substantially and vary among countries and regions. A 1-year follow-up study was performed to determine the incidence, kinetics and influencing factors of C. difficile intestinal colonization. METHODS: Twenty-nine healthy infants (14 girls and 15 boys) living at home with their parents in Handan City were followed by survey from birth to 1 year of age, specifically from October 2014 through December 2015. C. difficile isolates were typed by PCR ribotyping and analyzed for the presence of toxin genes. RESULTS: During the follow-up study period in the first year of life, 20 of the 29 total enrolled infants acquired C. difficile. A total of 437 fecal samples were obtained, and 111 (25.4%) samples contained C. difficile, including 79 (71.2%) toxigenic strains. The toxigenic isolates comprised six PCR ribotypes, and two PCR ribotypes were identified as nontoxigenic strains. CONCLUSION: Our study showed that C. difficile colonization increase with age during the 12-month period, and the dominant toxigenic types of C. difficile isolates in infants were those involved in long-term colonization. Feeding patterns may affect the dynamic progress of C. difficile colonization.
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Portador Sano/epidemiología , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Infecciones por Clostridium/epidemiología , Biodiversidad , China/epidemiología , Clostridioides difficile/aislamiento & purificación , ADN Bacteriano , Heces/microbiología , Conducta Alimentaria , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Incidencia , Lactante , Recién Nacido , Intestinos/microbiología , Masculino , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S , RibotipificaciónRESUMEN
Acid stress is one of the most common adverse conditions during fermentation of fruit wines, and the acid tolerance of yeasts is, therefore, critical for fruit wine production. However, the biological mechanism underlying the acquired tolerance of yeasts against acid stress is poorly understood. We have previously obtained an evolved Saccharomyces cerevisiae strain ET008-c54 with increased tolerance against acid stress, and potentially, it serves as a promising yeast strain for greengage wine fermentation. In the current study, we further revealed the alterations responsible for the adaptation of ET008-c54 to low pH by whole-genome re-sequencing, transcriptomic, and metabolic analyses. Results confirmed the outstanding fermenting performance of ET008-c54 at low pH as compared with the parental ET008. More specifically, the growth rate of ET008-c54 at low pH was increased by 6.24 times and the fermentation time was shortened by 70%. Differences were also observed in the physiology of the strains through ergosterol, H+-ATPase activity, and aroma determinations. By integrating both RNA-seq and whole-genome re-sequencing data, we demonstrated some metabolic pathways in ET008-c54, namely ergosterol synthesis and ferrous iron uptake, in which several acid-responsive genes were involved being upregulated. Also, upregulation of the pathways responsible for aroma compound formation, including fatty acid ethyl ester synthesis and aromatic amino acid biosynthesis, was identified. Thus, the enhanced fermentation ability of ET008-c54 at low pH should be, at least partly, contributed by the altered gene expressions associated with the aforementioned pathways. By elucidating the biological mechanism of yeasts against acid stress, this current study allows better-defined targets for future studies of genetic improvement of wine yeasts and enhancement of the fermentation processes. KEY POINTS: ⢠Metabolic analysis confirmed the excellent fermentation performance of ET008-c54. ⢠Acid tolerance genes for ergosterol synthesis and ferrous iron uptake were upregulated. ⢠Aroma genes for fatty acid ethyl ester and aromatic amino acid synthesis were upregulated.
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Vino , Fermentación , Frutas , Genómica , Saccharomyces cerevisiae/genética , Transcriptoma , Vino/análisisRESUMEN
Acid tolerance and aroma profile are crucial factors for wine production in Saccharomyces cerevisiae. However, most wine yeasts to date fail to endure low-pH environments, therefore resulting in problems such as lengthened fermentation and poor flavor during acidic fruit wine production. In the present study, we established a multiple-step screening strategy, which was composed of atmospheric and room temperature plasma (ARTP), high-throughput screening (HTS), and laboratory adaptive evolution (ALE), to screen yeast strains for potential wine-producing with enhanced performances during low pH conditions. Importantly, we obtained the S. cerevisiae strain from the mutant library, ET008-c54, which displayed exhibited excellent performances in survival rate, fermentation time, aroma profile, and genetic stability. More specifically, the survival rate of ET008-c54 at low pH was increased by 10-fold, the fermentation time of greengage plum wine was shortened by about 70%, and the content of main aroma compounds was significantly increased by 52%. Collectively, we demonstrate the practical application of the screening platform designed for discovering mutant strains in winemaking technology.
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Ácidos/metabolismo , Odorantes/análisis , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Evolución Molecular Dirigida , Fermentación , Ensayos Analíticos de Alto Rendimiento , Concentración de Iones de Hidrógeno , Mutagénesis , Fenotipo , Saccharomyces cerevisiae/crecimiento & desarrollo , Vino/análisis , Vino/microbiologíaRESUMEN
Cardiovascular disease (CVD), cancer and diabetes are serious threat to human health and more and more aroused people's attention. It is important to find the safe and effective prevention and treatment methods for the three deadly diseases. At present, a generally attention in the possible positive effects of edible berries for the three deadly diseases has been noted. Berry phytochemical compounds regulate different signaling pathways about cell survival, growth and differentiation. They contribute to the prevention and treatment of CVD, cancer and diabetes. This article reviews previous experimental evidence, several common berry phytochemical compounds and their possible mechanisms involved in three deadly diseases were summarized.
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Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus/prevención & control , Diabetes Mellitus/terapia , Frutas/química , Neoplasias/prevención & control , Neoplasias/terapia , Fitoquímicos/uso terapéutico , Antioxidantes/química , Humanos , Extractos Vegetales/uso terapéutico , Polifenoles/química , Transducción de Señal/efectos de los fármacosRESUMEN
Multienzyme associations localized to specific subcellular sites are involved in several critical functions in cellular metabolism, such as plant survival and reproduction. To date, few multienzyme complexes involved in male fertility have been examined in Brassica napus Here, we reported that in B. napus, the members of a multienzyme complex work in an interaction pattern different from that in Arabidopsis thaliana for sporopollenin biosynthesis. 7365A, a male-sterile mutant with a relatively smooth anther cuticle, was found to have a dramatic reduction in both cutin monomers and wax composition. Proteomic comparison between the mutant 7365A and wild-type 7365B showed down-regulation of three sporopollenin biosynthetic enzymes, namely BnPKSA, BnPKSB and BnTKPR; these enzymes were tightly co-expressed with BnACOS5. BnPKSA and BnPKSB showed similar expression patterns but distinct accumulation levels, suggesting that they had partially distinct functions during sporopollenin biosynthesis. In vitro and in vivo analyses demonstrated that BnPKSB directly interacted with BnPKSA and BnACOS5, but no such interactions were found in the present investigation for BnTKPR1. Interestingly, the interaction between PKSA and PKSB has not been discovered in Arabidopsis, which may indicate a new interaction representing an additional efficient regulation method in B. napus Taken together, we propose that BnPKSA and BnPKSB may comprise a heterodimer combined with BnACOS5, constituting a sporopollenin metabolon in tapetal cells that is related to male reproductive development in B. napus.
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Brassica napus/enzimología , Regulación de la Expresión Génica de las Plantas , Complejos Multienzimáticos , Proteómica , Biopolímeros/biosíntesis , Biopolímeros/genética , Brassica napus/genética , Brassica napus/crecimiento & desarrollo , Brassica napus/ultraestructura , Carotenoides/biosíntesis , Carotenoides/genética , Regulación hacia Abajo , Flores/enzimología , Flores/genética , Flores/crecimiento & desarrollo , Flores/ultraestructura , Lípidos de la Membrana/metabolismo , Modelos Biológicos , Mutación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Multimerización de ProteínaRESUMEN
BACKGROUND: To investigate the in vitro and in vivo antitumor activity of dual PI3K/mTOR inhibitor BEZ235 (NVP-BEZ235) in HER2-positive gastric cancer. METHODS: HER2-positive breast cancer cell line (BT474), HER2-positive (NCI-N87 and SNU216), and HER2-negative (MKN45) gastric cancer cell lines were used in this study. Cell viability, cell cycle, and HER2 downstream signaling pathways were analyzed using the MTS assay, flow cytometry, and western blotting, respectively. For the in vivo experiments, HER2-positive gastric cancer patient-derived xenografts were treated with BEZ235 to assess its antitumor activity. RESULTS: The sensitivity of trastuzumab in BT474 cells was higher than that for NCI-N87 and SNU216 cells, which may be partially attributed to continuously active HER2 downstream signaling pathway. BEZ235 inhibited the proliferation of NCI-N87 and SNU216 cells in vitro in a dose-dependent manner by inducing the cell cycle arrest at the G1 phase. BEZ235 demonstrated greater inhibitory effects than trastuzumab, a unique targeted drug, in both the in vitro and in vivo set of experiments. Additionally, our results indicate that BEZ235 displayed some synergism with trastuzumab. BEZ235 exhibited its antitumor activity in gastric cancer by inhibiting important HER2 downstream signaling pathways, as indicated by the inhibition of phosphorylated AKT and S6. CONCLUSION: The present study has demonstrated, for the first time, the antitumor activity of BEZ235 against HER2-positive gastric cancer in patient-derived xenografts, as well its synergistic interaction with trastuzumab. These important findings can be utilized to facilitate the design of future clinical trials.
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Antineoplásicos/farmacología , Imidazoles/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Quinolinas/farmacología , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Ratones , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Trastuzumab/farmacología , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Genistein, a major isoflavone constituent in soybeans, has been reported to exhibit multiple anti-tumor effects, such as inducing cell cycle arrest, triggering apoptosis, and inactivating critical signaling pathways in a few human cancer cells. Here, we investigated the anti-tumor effects of genistein on the small-cell lung cancer (SCLC) cell line H446 and the underlying molecular mechanisms. H446 cells were treated with various concentrations of genistein, and experiments including CCK-8 assay, colony formation assay, flow cytometry analysis, wound healing assay, real-time polymerase chain reaction (PCR), western blot analysis, and plasmid transfection were used to investigate the influence of genistein on cell proliferation, migration ability, apoptosis, cell cycle progression, as well as the mRNA and protein alterations of FoxM1 pathway molecules. We found that genistein significantly inhibited the proliferation and migration ability of H446 cell, accompanied by apoptosis and G2/M phase cell cycle arrest. In addition, genistein enhanced the anti-proliferative effect of cisplatin on H446 cells. Importantly, genistein led to attenuation of the FoxM1 protein and down-regulated a series of FoxM1 target genes regulating cell cycle and apoptosis including Cdc25B, cyclin B1, and survivin. In addition, up-regulation of FoxM1 by cDNA transfection prior to genistein treatment could reduce genistein-induced H446 proliferation inhibition. Thus, for the first time, we demonstrated that genistein exerted multiple anti-tumor effects in H446 SCLC cell line at least partly mediated by the down-regulation of FoxM1. FoxM1 has the potential as a novel therapeutic agent in SCLC and is worthy of further study.
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Antineoplásicos/farmacología , Factores de Transcripción Forkhead/antagonistas & inhibidores , Genisteína/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/fisiología , Humanos , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
This study examines the differences in service level and coverage of public transit (PT) and private vehicles (PV) with multi-source data in Shanghai. To construct computable networks and address visual results, the constrained shortest path algorithm and a spatial grid accessibility model are employed to seek the optimal path for travelers to city key points. Travel time ratio of PV and PT is applied to reflect the competitiveness of the two modes over different areas of Shanghai. Results show that for PV, although the average travel time meets the needs of car travel, 51 % of the population cannot get to graded city centers within 45 min. In addition, the PV accessibility gradually weakens from the central city to the outside, highways and expressways may be feasible solutions. For PT, half of the population can't reach any city key points within two transfers, and almost all of these people live in the suburbs. Less than 30 % of the population can reach the city key points within 1 h, of which rail transit contributes more than conventional buses. Furthermore, the travel accessibility of PV is much better than that of PT. The average travel time ratio in all comparable grids is 2.04 for hubs, and 2.10 for graded city centers. For travels to graded city centers, the travel time ratio of suburbs is 35 % higher than that of central city, indicating that the inequity distribution of public transportation resources is worse in the suburbs than in the central city. This study also measures equity performance of groups based on spatial location and income level, and we find out that more core locations and higher income lead to higher accessibility. The gap among groups is significant, with a Gini coefficient over 0.5.
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Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.
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Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood-brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.
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Autofagia , Inflamasomas , Inflamación , Compuestos de Metilmercurio , Microglía , Proteína con Dominio Pirina 3 de la Familia NLR , Compuestos de Metilmercurio/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Autofagia/efectos de los fármacos , Ratones , Inflamasomas/metabolismo , Animales , Inflamación/inducido químicamente , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacosRESUMEN
With the acceleration of global aging and the rise in living standards, the achievement of healthy aging is becoming an imperative issue globally. Ginseng, a medicinal plant that has a long history of dietary intake and remarkable medicinal value, has become a research hotspot in the field of food and medicine. Ginsenosides, especially protopanaxadiol-type saponins and protopanaxatriol-type saponins, are among the most important active ingredients in ginseng. Ginsenosides have been found to exhibit powerful and diverse pharmacological activities, such as antiaging, antitumor, antifatigue and immunity enhancement activities. Their effects in antiaging mainly include (1) promotion of metabolism and stem cell proliferation, (2) protection of skin and nerves, (3) modulation of intestinal flora, (4) maintenance of mitochondrial function, and (5) enhancement of telomerase activity. The underlying mechanisms are primarily associated with the intervention of the signaling pathways in apoptosis, inflammation and oxidative stress. In this review, the mechanism of action of ginsenosides in antiaging as well as the potential values of developing ginsenoside-based functional foods and antiaging drugs are discussed.
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Sinomenine is an active substance extracted from the traditional Chinese medicine Sinomenium acutum. Sinomenine has been shown to mediate a wide range of pharmacological actions and is known to possess good anti-inflammatory, immunosuppressive, antitumor, neuroprotective, antiarrhythmic and other pharmacological effects. Understanding the underlying mechanisms and the association between the targets and the pharmaceutical effects on different diseases is crucial to the discovery and design of new treatment strategies. In this review, we aim to give a systematic and comprehensive overview of the research progress of sinomenine over the past 20 years. We first describe the metabolism of sinomenine in vivo and then summarize the pharmacological actions of sinomenine on different diseases. Furthermore, the potential binding properties of sinomenine and the potential of developing new sinomenine-based drugs are also reviewed.