RESUMEN
The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.
Asunto(s)
Metagenoma , Microbiota , Ovinos/genética , Animales , Transcriptoma , Rumen , Rumiantes/genéticaRESUMEN
Aging is linked to greater susceptibility to chronic inflammatory diseases, several of which, including periodontitis, involve neutrophil-mediated tissue injury. Here we found that aging-associated periodontitis was accompanied by lower expression of Del-1, an endogenous inhibitor of neutrophil adhesion dependent on the integrin LFA-1, and by reciprocal higher expression of interleukin 17 (IL-17). Consistent with that, IL-17 inhibited gingival endothelial cell expression of Del-1, thereby promoting LFA-1-dependent recruitment of neutrophils. Young Del-1-deficient mice developed spontaneous periodontitis that featured excessive neutrophil infiltration and IL-17 expression; disease was prevented in mice doubly deficient in Del-1 and LFA-1 or in Del-1 and the IL-17 receptor. Locally administered Del-1 inhibited IL-17 production, neutrophil accumulation and bone loss. Therefore, Del-1 suppressed LFA-1-dependent recruitment of neutrophils and IL-17-triggered inflammatory pathology and may thus be a promising therapeutic agent for inflammatory diseases.
Asunto(s)
Pérdida de Hueso Alveolar/inmunología , Proteínas Portadoras/metabolismo , Interleucina-17/antagonistas & inhibidores , Interleucina-17/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Periodontitis/metabolismo , Envejecimiento/inmunología , Animales , Proteínas de Unión al Calcio , Proteínas Portadoras/inmunología , Proteínas Portadoras/farmacología , Adhesión Celular/efectos de los fármacos , Moléculas de Adhesión Celular , Células Endoteliales/efectos de los fármacos , Células Endoteliales/inmunología , Femenino , Integrinas/antagonistas & inhibidores , Integrinas/inmunología , Integrinas/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Interleucina-17/inmunología , Antígeno-1 Asociado a Función de Linfocito/inmunología , Antígeno-1 Asociado a Función de Linfocito/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Atrofia Periodontal/inmunología , Atrofia Periodontal/metabolismo , Periodontitis/inmunología , Periodontitis/terapia , Receptores de Interleucina-17/deficiencia , Receptores de Interleucina-17/metabolismoRESUMEN
Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
Asunto(s)
MicroARNs , Células de Sertoli , 1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Actinas/genética , Actinas/metabolismo , Animales , Supervivencia Celular/genética , Masculino , Mamíferos/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Ratas , Ratas Sprague-Dawley , Células de Sertoli/metabolismo , Espermatogénesis/genética , Porcinos , Uniones Estrechas/metabolismoRESUMEN
Sperm associated antigen 6 (SPAG6) acts as a scaffolding protein in the center of the flagellar axoneme and has an impact on the maturation of the motility of mammalian sperm flagella and the maintenance of sperm structure. In our previous research, SPAG6 c.900 T>C in exon 7 and exon 7 skipped transcript was identified by analyzing RNA-seq data of testicular tissues from 60 day (sexually immature) and 180 day (sexually mature) Large White boars. Herein, we found porcine SPAG6 c.900 T>C to be associated with semen quality traits in Duroc, Large White and Landrace pigs. SPAG6 c.900 C can generate a new splice acceptor site, inhibit the occurrence of SPAG6 exon 7 skipping to a certain extent, thereby promote the growth of Sertoli cells and maintain the normal blood-testis barrier function. This study provides new insights into the molecular regulation of spermatogenesis and a new genetic marker for the improvement of semen quality in pigs.
Asunto(s)
Sitios de Empalme de ARN , Análisis de Semen , Porcinos/genética , Masculino , Animales , Análisis de Semen/veterinaria , Barrera Hematotesticular , Semen , Espermatozoides , MamíferosRESUMEN
Spermatogenesis is the developmental process that produces spermatozoa. The aim of this study was to investigate the single nucleotide polymorphisms (SNPs) within C7H15orf39 and NOS2 genes and to determine the correlations between two SNPs and semen quality in Duroc boars (n = 604). The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method was used for genotyping the selected two nonsynonymous SNPs. The significant correlation was observed between two SNPs (rs80969873: g.58385473 G > A within C7H15orf39; rs325865291: g.44175445 G > A within NOS2) and semen traits in Duroc boars. This study indicates the SNPs in C7H15orf39 and NOS2 may be the potential molecular marker for improving the semen quality traits in Duroc boars.
Asunto(s)
Polimorfismo de Nucleótido Simple , Análisis de Semen , Porcinos/genética , Animales , Masculino , Análisis de Semen/veterinaria , Polimorfismo de Nucleótido Simple/genética , Semen , Espermatozoides , Espermatogénesis/genéticaRESUMEN
In this study, we newly sequenced and analyzed the complete mitochondrial genomes of five genera and six species in Gargarini: Antialcidas floripennae, Centrotoscelus davidi, Kotogargara minuta, Machaerotypus stigmosus, Tricentrus fulgidus, and Tricentrus gammamaculatus. The mitochondrial genomes contain 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. The lengths of the mitochondrial genomes are 15,253 bp to 15,812 bp, and the AT contents of the obtained mitogenomes indicate a strong AT bias, ranging from 75.8% to 78.5%. The start codons of all PCGs show that most start with a typical ATN (ATA/T/G/C) codon and less start with T/GTG; the stop codon TAA is frequently used, and TAG and a single T are less used. In Gargarini mitogenomes, all tRNA genes can be folded into the canonical cloverleaf secondary structure, except for trnaS1, which lacks a stable dihydrouridine (DHU) stem and is replaced by a simple loop. At the same time, the phylogenetic analysis of the tribe Gargarini based on sequence data of 13 PCGs from 18 treehopper species and four outgroups revealed that the 10 Gargarini species form a steady group with strong support and form a sister group with Leptocentrini, Hypsauchenini, Centrotini, and Leptobelini. Diversification within Gargarini is distinguished by a Later Cretaceous divergence that led to the rapid diversification of the species. Moreover, the ancestral state reconstructions analysis showed the absence of the suprahumeral horn, which was confirmed as the ancestor characteristic of the treehopper, which has evolved from simple to complex. Our results shed new light specifically on the molecular and phylogenetic evolution of the pronotum in Gargarini.
Asunto(s)
Genoma Mitocondrial , Hemípteros , Animales , Hemípteros/genética , Filogenia , ARN de Transferencia/genética , ARN de Transferencia/química , Codón de Terminación , ARN Ribosómico/genética , ARN Ribosómico/químicaRESUMEN
In a healthy body, reactive oxygen species (ROS) and antioxidants remain balanced. When the balance is broken toward an overabundance of ROS, oxidative stress appears and may lead to oocyte aging. Oocyte aging is mainly reflected as the gradual decrease of oocyte quantity and quality. Here, we aim to review the relationship between oxidative stress and oocyte aging. First, we introduced that the defective mitochondria, the age-related ovarian aging, the repeated ovulation, and the high-oxygen environment were the ovarian sources of ROS in vivo and in vitro. And we also introduced other sources of ROS accumulation in ovaries, such as overweight and unhealthy lifestyles. Then, we figured that oxidative stress may act as the "initiator" for oocyte aging and reproductive pathology, which specifically causes follicular abnormally atresia, abnormal meiosis, lower fertilization rate, delayed embryonic development, and reproductive disease, including polycystic ovary syndrome and ovary endometriosis cyst. Finally, we discussed current strategies for delaying oocyte aging. We introduced three autophagy antioxidant pathways like Beclin-VPS34-Atg14, adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), and p62-Keap1-Nrf2. And we also describe the different antioxidants used to combat oocyte aging. In addition, the hypoxic (5% O2 ) culture environment for oocytes avoiding oxidative stress in vitro. So, this review not only contribute to our general understanding of oxidative stress and oocyte aging but also lay the foundations for the therapies to treat premature ovarian failure and oocyte aging in women.
Asunto(s)
Envejecimiento/fisiología , Oocitos/metabolismo , Estrés Oxidativo/fisiología , Reproducción/fisiología , Animales , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
Sertoli cells are the only somatic cells in the seminiferous epithelium which directly contact with germ cells. Sertoli cells exhibit polarized alignment at the basal membrane of seminiferous tubules to maintain the microenvironment for growth and development of germ cells, and therefore play a crucial role in spermatogenesis. Androgens exert their action through androgen receptor (AR) and AR signalling in the testis is essential for maintenance of spermatogonial numbers, blood-testis barrier integrity, completion of meiosis, adhesion of spermatids and spermiation. In the present study, we demonstrated that AR gene could promote the proliferation of immature porcine Sertoli cells (ST cells) and the cell cycle procession, and accelerate the transition from G1 phase into S phase in ST cells. Meanwhile, miR-124a could affect the proliferation and cell cycle procession of ST cells by targeting 3'-UTR of AR gene. Furthermore, AR bound to the RNF4 via AR DNA-binding domain (DBD) and we verified that RNF4 was necessary for AR to regulate the growth of ST cells. Above all, this study suggests that AR regulates ST cell growth via binding to RNF4 and miR-124a, which may help us to further understand the function of AR in spermatogenesis.
Asunto(s)
Proliferación Celular/genética , Proteínas Nucleares/genética , Receptores Androgénicos/genética , Células de Sertoli/metabolismo , Regiones no Traducidas 3'/genética , Animales , Ciclo Celular , Línea Celular , Proteínas de Unión al ADN/genética , Expresión Génica , Masculino , MicroARNs/metabolismo , Dominios Proteicos , Células de Sertoli/fisiología , Porcinos , Factores de Transcripción/genéticaRESUMEN
Four new tetrahydroanthracene derivatives (1, 3-5) and a known antibiotic, A-39183A (2), were discovered from the marine-sponge-derived actinomycete Streptomyces fumigatiscleroticus HDN10255. Their structures including absolute configurations were elucidated based upon MS and NMR spectroscopic data, ECD calculations, and biogenetic considerations. Compounds 2 and 4 showed considerable cytotoxicity with the best IC50 value of 1.8 µM against HeLa cells.
Asunto(s)
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Streptomyces/química , Animales , Línea Celular Tumoral , Células HeLa , Humanos , Isomerismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Poríferos/microbiologíaRESUMEN
Generation of durable tumor-specific immune response without isolation and expansion of dendritic cells or T cells ex vivo remains a challenge. In this study, we investigated the impact of nanoparticle-mediated photothermolysis in combination with checkpoint inhibition on the induction of systemic antitumor immunity. Photothermolysis based on near-infrared light-absorbing copper sulfide nanoparticles and 15-ns laser pulses combined with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) increased tumor infiltration by antigen-presenting cells and CD8-positive T lymphocytes in the B16-OVA mouse model. Moreover, combined photothermolysis, polymeric conjugate of the Toll-like receptor 9 agonist CpG, and αPD-1 significantly prolonged mouse survival after re-inoculation of tumor cells at a distant site compared to individual treatments alone in the poorly immunogenic syngeneic ID8-ip1-Luc ovarian tumor model. Thus, photothermolysis is a promising interventional technique that synergizes with Toll-like receptor 9 agonists and immune checkpoint inhibitors to enhance the abscopal effect in tumors.
Asunto(s)
Melanoma Experimental/tratamiento farmacológico , Terapia Fototérmica , Receptor de Muerte Celular Programada 1/genética , Receptor Toll-Like 9/genética , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunidad Innata/efectos de los fármacos , Inmunoterapia/métodos , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Nanopartículas/química , Nanopartículas/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Receptor Toll-Like 9/agonistasRESUMEN
Litter size is an important economic traits in pigs. SLA-11 gene is a member of SLA (swine leukocyte antigen) complex. In our previous study, the SLA-11 gene was differentially expressed in PMSG-hCG stimulated preovulatory ovarian follicles of Chinese Taihu and Large White sows. Here, we identified two mutations (c.754-132 T > C and c.1421 + 38 T > C) in SLA-11 gene and analyzed the associations of two SNPs with litter size traits in Large White (n = 263) and DIV (n = 117) sows. The results showed that in Large White pigs, SLA-11 c.754-132 CC sows produced 0.74 and 0.87 more pigs per litter for TNB and NBA of all parities than did TT sows (p < .05); In DIV pigs, SLA-11 c.754-132 CC sows produced 1.17 more pigs per litter for TNB of all parities than did TC sows (p < .05). In Large White pigs, SLA-11 c.1421 + 38 CC sows produced 0.9 more pigs per litter for TNB of all parities than did TT sows (p < .05), while in DIV pigs SLA-11 c.1421 + 38 CC sows produced 0.84 and 0.7 less pigs per litter for TNB and NBA of all parities than did TT sows (p < .05). Our research indicated that SLA-11 mutations were potential molecular markers for improving the litter size traits in pigs.
Asunto(s)
Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo de Nucleótido Simple/genética , Reproducción , Porcinos/genética , Animales , Gonadotropina Coriónica/farmacología , Combinación de Medicamentos , Femenino , Gonadotropinas Equinas/farmacología , Tamaño de la Camada/genética , Mutación , Folículo Ovárico/efectos de los fármacos , Embarazo , Porcinos/fisiologíaRESUMEN
To select new Large White line with high number of piglets born, genotypes of estrogen receptor (ESR), the follicle stimulating hormone ß subunit (FSHß), catenin alpha like 1 (CTNNAL1) and miR-27a were tested in 472 Large White sows. The associations of different genotypes with litter size traits were also studied. The results showed ESRBB and FSHßBB sows produced 0.41-1.49 more pigs per litter (p < .05) for total number born (TNB) and number born alive (NBA) than did other corresponding genotypes. TNB of CTNNAL1CG sows is 0.50 more pigs per litter (p < .05) than that of CTNNAL1GG sows with the dominance effect of 0.25 pigs per litter (p < .05). miR-27aBB sows had a less estimated breeding value (EBV) to TNB and had a more number of mummified pigs (NM) than did miR-27aAA or miR-27aAB sows (p < .05). Therefore, ESRB, FSHßB, CTNNAL1G, miR-27aA allele was favorable for litter size traits. Furthermore, combined genetic effect analysis showed ESRAAFSHßBB, ESRAACTNNAL1CG, ESRAAmiR-27aAA, FSHßBBCTNNAL1CC, FSHßBBmiR-27aAA and CTNNAL1CG miR-27aAB was the favorable combined genotype for litter size traits. These results identified favorable alleles and genotypes for litter size traits and suggested a potential selection scheme for litter size in Large White pigs.
Asunto(s)
Hormona Folículo Estimulante de Subunidad beta/genética , Tamaño de la Camada/genética , MicroARNs/genética , Receptores de Estrógenos/genética , Porcinos/genética , alfa Catenina/genética , Alelos , Animales , Cruzamiento , Femenino , Marcadores Genéticos , Genotipo , Polimorfismo de Nucleótido Simple , EmbarazoRESUMEN
Spermatogenesis is a complex process regulated by many genes. In this study, H2AFZ, RNF4 and NR4A1 genes were selected as candidate genes for boar semen quality traits based on their functions during spermatogenesis, and the associations of three loci (H2AFZ c.192 + 210-192 + 213delCGAT, RNF4 c.374 + 358 T > C and NR4A1 c.956 + 796 A > G) with sperm quality traits were analyzed in Duroc (n = 185), Large White (n = 87) and Landrace (n = 49) pig populations. The results showed H2AFZ c.192 + 210-192 + 213delCGAT AA boars produced 1.52% lower abnormal sperm rate (ASR) than AB boars in Landrace pigs (p < 0.05); RNF4 c.374 + 358 TC boars produced 0.31 × 108/ml higher sperm concentration (SCON) than CC boars (p < 0.05) in Large White pigs; NR4A1 c.956 + 796 A > G was associated with ASR in Duroc and Large White pigs and was associated with sperm motility (MOT) in Large White and Landrace pigs. This study indicated the H2AFZ, RNF4 and NR4A1 loci were the potential molecular markers for improving the semen quality traits in boars.
Asunto(s)
Histonas/genética , Proteínas Nucleares/genética , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Espermatogénesis/genética , Porcinos/genética , Factores de Transcripción/genética , Alelos , Animales , Estudios de Asociación Genética , Sitios Genéticos , Genotipo , Masculino , Polimorfismo de Nucleótido Simple , Análisis de Semen , Recuento de Espermatozoides , Motilidad Espermática/genéticaRESUMEN
Female fertility potential is based on the development and growth of ovarian follicles. Our previous study showed that miR-17-5p was significantly differently expressed in pre-ovulatory ovarian follicles of Large White (LW) and Chinese Taihu (CT) sows. In the present study, we investigated the role of miR-17-5p in ovarian follicle development. We demonstrated that miR-17-5p overexpression significantly decreased the luciferase reporter activity containing the E2F transcription factor 1 (E2F1) 3'untranslated region (3'UTR) and suppressed the E2F1 expression, whereas the miR-17-5p inhibition increased the E2F1 expression in porcine granulosa cells (pGCs). Meanwhile, miR-17-5p overexpression or E2F1 knockdown promoted cell growth, follicular development marker genes (LHR, CYP19A1 and AREG) expression and oestradiol synthesis, and miR-17-5p inhibition suppressed cell growth, follicular development marker genes (LHR, CYP19A1 and AREG) expression and oestradiol synthesis in pGCs. Furthermore, E2F1 knockdown increased CYP19A1 promoter activity. This study suggests that miR-17-5p regulates pGC growth and oestradiol synthesis by targeting E2F1 gene.
Asunto(s)
Proliferación Celular , Factor de Transcripción E2F1/genética , Células de la Granulosa/metabolismo , MicroARNs/metabolismo , Regiones no Traducidas 3' , Animales , Estradiol/biosíntesis , Femenino , Técnicas de Silenciamiento del Gen , MicroARNs/genética , Folículo Ovárico/metabolismo , PorcinosRESUMEN
Acidic microenvironment, particularly acid-sensing ion channel 1a (ASIC1a), has been reported to promote carcinoma cell proliferation as well as migration. In this study, we explored the effect of ASIC1a on migration and invasion of gastric carcinoma (GC). ASIC1a expression levels were examined in paired GC and adjacent normal tissues from 16 patients by immunohistochemistry. Reverse transcription real-time PCR and immunoblotting were conducted to assess the ASIC1a expression levels in the GC cell line AGS after transfection with ASIC1a small hairpin RNA (shRNA). Wound healing and transwell invasion assays were utilized to detect metastasis and invasion following ASIC1a silencing. Tumor formation was used to detect the role of ASIC1a in tumorigenicity in vivo. It was found that ASIC1a expression level was significantly higher in GC tissues showing postoperative metastasis compared with non-metastasis and non-tumor tissues. Moreover, silencing of ASIC1a with shRNA significantly down-regulated ASIC1a expression and reduced GC cell migration and invasion. A moderately acidic extracellular environment inhibited GC cell viability. Furthermore, ASIC1a shRNA caused inhibition of tumorigenicity in vivo. Our study is the first report of attenuating the malignant phenotype of GC in vitro and in vivo by suppressing ASIC1a, and suggests a novel approach to study the relationship between ASICs and GC cell migration and invasion.
Asunto(s)
Canales Iónicos Sensibles al Ácido/genética , Movimiento Celular/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/genética , Canales Iónicos Sensibles al Ácido/metabolismo , Adulto , Anciano , Animales , Línea Celular Tumoral , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Interferencia de ARN , Tratamiento con ARN de Interferencia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Many factors are involved in parturition, such as apoptosis, inflammatory mediators, and hormones. Previous studies indicated that HSP70 directly or indirectly regulates apoptosis, inflammatory immune response and hormone stimulus. To gain new insights into molecular mechanism underlying HSP70 for regulating parturition, we overexpressed and knocked down two representative members of HSP70 (HSPA1A and HSPA8) through transfection of their recombinant plasmid and si-RNA separately in WISH (human amniotic epithelial) cells. The expression changes of several pathways' marker genes were investigated by Western blotting and quantitative real-time PCR (qRT-PCR). Results showed extreme expression changes in the genes of IL-8 and ESR2. HSP70 was found to stimulate estrogen response by regulating ESR2 through ERK1/2 after treating WISH cells with the special phosphorylation inhibitor of ERK1/2 and analyzing the changes of E2 concentration by ELISA. HSP70 was also observed to contribute to preterm birth after administering the special inhibitor of HSP70-PFT-µ with LPS-induced preterm birth mouse model. Overall, HSP70 induces parturition through stimulating immune inflammatory and estrogen response. The balanced HSP70 expression could ensure a smooth parturition, while the imbalanced expression may cause a pathological state like preterm.
Asunto(s)
Receptor beta de Estrógeno/metabolismo , Proteínas del Choque Térmico HSC70/fisiología , Proteínas HSP70 de Choque Térmico/fisiología , Parto/metabolismo , Amnios/metabolismo , Animales , Apoptosis , Células Epiteliales/metabolismo , Femenino , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Sistema Inmunológico , Inflamación , Interleucina-8/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Endogámicos BALB C , Fosforilación , Conformación Proteica , Distribución Aleatoria , Proteínas Recombinantes/metabolismoRESUMEN
Denitrification is considered to be the critical process in removing reactive nitrogen in estuarine ecosystems. In the present study, the abundance, diversity, and community structure of nirK- and nirS-type denitrifiers were compared in sediments from the Yellow River estuary. Quantitative polymerase chain reaction showed that the 2 types of denitrifiers exhibited different distribution patterns among the samples, indicating their distinct habitat preference. Phylogenetic analysis revealed that most of the sequences from clusters I, III, IV, and V for nirK-type denitrifiers were dominant and were distributed at sites where dissolved oxygen (DO) was lower, and the sequences in the other clusters were dominant at sites with higher DO. However, there was no spatially heterogeneous distribution for the nirS-type denitrifier community. Canonical correlation analysis and correlation analysis demonstrated that the community structure of nirK was more responsive to environmental factors than was that of nirS. Inversely, the abundance and α-diversity targeting nirS gene could be more easily influenced by environmental parameters. These findings can extend our current knowledge about the distribution patterns of denitrifying bacteria and provide a basic theoretical reference for the dynamics of denitrifying communities in estuarine ecosystem of China.
Asunto(s)
Nitrito Reductasas/genética , Proteobacteria/metabolismo , Microbiología del Agua , China , Desnitrificación , Ecosistema , Estuarios , Genes Bacterianos , Sedimentos Geológicos/microbiología , Nitrógeno , Filogenia , Proteobacteria/enzimología , Proteobacteria/genética , RíosRESUMEN
There are close exchanges between sediment and water in estuaries; however, the patterns of prokaryotic community assembly in these two habitat types are still unclear. This study investigated the bacterial and archaeal abundance, diversity, and community composition in the sediment and the overlying water of the Yellow River estuary. Notably higher prokaryotic abundance and diversity were detected in the sediment than in the water, and bacterial abundance and diversity were remarkably higher than those of archaea. Furthermore, the ratio of bacterial to archaeal 16S rRNA gene abundance was significantly lower in the sediment than in the water. Bacterial communities at different taxonomic levels were apparently distinct between the sediment and water, but archaeal communities were not. The most dominant bacteria were affiliated with Deltaproteobacteria and Gammaproteobacteria in sediment and with Alphaproteobacteria and Betaproteobacteria in water. Euryarchaeota and Thaumarchaeota were the most abundant archaea in both habitats. Although distinct prokaryotic distribution patterns were observed, most of the dominant bacteria and archaea present were related to carbon, nitrogen, and sulfur cycling processes, such as methanogenesis, ammonia oxidation, and sulfate reduction. Unexpectedly, prokaryotes from the water showed a higher sensitivity to environmental factors, while only a few factors affected sediment communities. Additionally, some potential co-occurrence relationships between prokaryotes were also found in this study. These results suggested distinct distribution patterns of bacterial and archaeal communities between sediment and overlying water in this important temperate estuary, which may serve as a useful community model for the further ecological and evolutionary study of prokaryotes in estuarine ecosystems.
Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Biota , Estuarios , Agua Dulce/microbiología , Sedimentos Geológicos/microbiología , Ríos/microbiología , Archaea/genética , Archaea/aislamiento & purificación , Bacterias/genética , Bacterias/aislamiento & purificación , Análisis por Conglomerados , ADN de Archaea/química , ADN de Archaea/genética , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: CD4+CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) accumulate in malignant tumors and negatively regulate antitumor immunity. However, the clinical significance of Tregs in HCC remains unclear. To determine the prognostic value of Tregs, we conducted a retrospective study on 264 patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE). METHODS: We measured the proportion of peripheral blood Tregs in 105 healthy donors and 264 HCC patients (stage B) prior to and following TACE between 2005 and 2007. All HCC patients were followed up until December 2012. The correlations between the proportion of Tregs and clinicopathologic factors were analyzed, and long-term survival rate after TACE according to the percentage of Tregs was assessed by univariate and multivariate analyses. RESULTS: The 1-, 2-, 3-, 4- and 5-year cumulative survival rates were 62.1%, 32.6%, 16.5%, 10.4% and 6.9%, respectively, and the median survival time was 19.0 months. The cumulative survival rate was significantly lower in patients with higher levels of peripheral blood Treg cells compared to those with lower Treg levels (p<0.001). Furthermore, we found that both pre- and post-TACE peripheral blood Treg levels showed significant negative association with overall survival time (p<0.001). CONCLUSIONS: Elevated peripheral blood CD4+CD25+FOXP3+Treg levels are an independent predictive factor of poor survival after TACE for HCC (stage B) patients. These results suggest that targeting Tregs may improve patient outcomes, and provide a strong rationale for testing these approaches in future immunotherapy-based clinical trials.
Asunto(s)
Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD4/metabolismo , Recuento de Linfocito CD4 , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.