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Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.
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Neoplasias , Estructuras Linfoides Terciarias , Microambiente Tumoral , Humanos , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/patología , Microambiente Tumoral/inmunología , Animales , Inmunoterapia/métodos , Linfocitos B/inmunología , Linfocitos T/inmunologíaRESUMEN
The combined cadmium (Cd) and acid rain pollution poses a significant threat to the global ecological environment. Previous studies on the combined adverse effects have predominantly focused on the aboveground plant physiological responses, with limited reports on the microbial response in the rhizosphere soil. This study employed Populus beijingensis seedlings and potting experiments to simulate the impacts of combined mild acid rain (pH=4.5, MA) or highly strong acid rain (pH=3.0, HA), and soil Cd pollution on the composition and diversity of microbial communities, as well as the physiochemical properties in the rhizosphere soil. The results showed that Cd decreased the content of inorganic nitrogen, resulting in an overall decrease of 49.10â¯% and 46.67â¯% in ammonium nitrogen and nitrate nitrogen, respectively. Conversely, acid rain was found to elevate the content of total potassium and soil organic carbon by 4.68â¯%-6.18â¯% and 8.64-19.16â¯%, respectively. Additionally, simulated acid rain was observed to decrease the pH level by 0.29-0.35, while Cd increased the pH level by 0.11. Moreover, Cd alone reduced the rhizosphere bacterial diversity, however, when combined with acid rain, regardless of its intensity, Cd was observed to increase the diversity. Fungal diversity was not influenced by the acid rain, but Cd increased fungal diversity to some extend under HA as observed in bacterial diversity. In addition, composition of the rhizosphere bacterial community was primarily influenced by the inorganic nitrogen components, while the fungal community was driven mainly by soil pH. Furthermore, "Metabolism" was emerged as the most significant bacterial function, which was markedly affected by the combined pollution, while Cd pollution led to a shift from symbiotroph to other trophic types for fungi. These findings suggest that simulated acid rain has a mitigating effect on the diversity of rhizosphere bacteria affected by Cd pollution, and also alters the trophic type of these microorganisms. This can be attributed to the acid rain-induced direct acidic environment, as well as the indirect changes in the availability or sources of carbon, nitrogen, or potassium.
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Lluvia Ácida , Cadmio , Nitrógeno , Populus , Rizosfera , Plantones , Microbiología del Suelo , Contaminantes del Suelo , Cadmio/toxicidad , Cadmio/análisis , Populus/efectos de los fármacos , Populus/microbiología , Populus/crecimiento & desarrollo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/microbiología , Nitrógeno/análisis , Suelo/química , Microbiota/efectos de los fármacos , Concentración de Iones de Hidrógeno , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacosRESUMEN
BACKGROUND: Bone development involves the rapid proliferation and differentiation of osteogenic lineage cells, which makes accurate chromosomal segregation crucial for ensuring cell proliferation and maintaining chromosomal stability. However, the mechanism underlying the maintenance of chromosome stability during the rapid proliferation and differentiation of Prx1-expressing limb bud mesenchymal cells into osteoblastic precursor cells remains unexplored. METHODS: A transgenic mouse model of RanGAP1 knockout of limb and head mesenchymal progenitor cells was constructed to explore the impact of RanGAP1 deletion on bone development by histomorphology and immunostaining. Subsequently, G-banding karyotyping analysis and immunofluorescence staining were used to examine the effects of RanGAP1 deficiency on chromosome instability. Finally, the effects of RanGAP1 deficiency on chromothripsis and bone development signaling pathways were elucidated by whole-genome sequencing, RNA-sequencing, and qPCR. RESULTS: The ablation of RanGAP1 in limb and head mesenchymal progenitor cells expressing Prx1 in mice resulted in embryonic lethality, severe cartilage and bone dysplasia, and complete loss of cranial vault formation. Moreover, RanGAP1 loss inhibited chondrogenic or osteogenic differentiation of mesenchymal stem cells (MSCs). Most importantly, we found that RanGAP1 loss in limb bud mesenchymal cells triggered missegregation of chromosomes, resulting in chromothripsis of chromosomes 1q and 14q, further inhibiting the expression of key genes involved in multiple bone development signaling pathways such as WNT, Hedgehog, TGF-ß/BMP, and PI3K/AKT in the chromothripsis regions, ultimately disrupting skeletal development. CONCLUSIONS: Our results establish RanGAP1 as a critical regulator of bone development, as it supports this process by preserving chromosome stability in Prx1-expressing limb bud mesenchymal cells.
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Diferenciación Celular , Inestabilidad Cromosómica , Esbozos de los Miembros , Células Madre Mesenquimatosas , Animales , Ratones , Desarrollo Óseo , Condrogénesis/genética , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/genética , Esbozos de los Miembros/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratones Noqueados , Osteogénesis/genética , Transducción de SeñalRESUMEN
The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (RhebBAD KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-κB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from RhebBAD KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the RhebBAD KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis.
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Sensory neuron membrane proteins (SNMPs) play important roles in insect chemoreception and SNMP1s have been reported to be essential in detecting sex pheromones in Drosophila and some lepidopteran species. However, SNMPs for Cyrtotrachelus buqueti (Coleoptera: Curculionidae), a major insect pest of bamboo plantations, remain uncharacterized. In this study, a novel SNMP gene, CbuqSNMP1b, from C. buqueti was functionally characterized. The expression of CbuqSNMP1b was significantly higher in antennae than in other tissues of both sexes and the expression level was significantly male-biased. Additionally, CbuqSNMP1b showed significantly higher transcription levels in the adult stage and very low transcription levels in other stages, suggesting that CbuqSNMP1b is involved in the process of olfaction. Fluorescence binding assays indicated that CbuqSNMP1b displayed the strongest binding affinity to dibutyl phthalate (Ki = 9.03 µM) followed by benzothiazole (Ki = 11.59 µM) and phenol (Ki = 20.95 µM) among fourteen C. buqueti volatiles. Furthermore, molecular docking revealed key residues in CbuqSNMP1b that interact with dibutyl phthalate, benzothiazole, and phenol. In conclusion, these findings will lay a foundation to further understand the olfactory mechanisms of C. buqueti and promote the development of novel methods for controlling this pest.
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Both acid and alkaline purple soils in China are increasingly affected by Cd contamination. The selection of fast-growing trees suitable for remediating different soil types is urgent, yet there is a severe lack of relevant knowledge. In this study, we conducted a controlled pot experiment to compare the growth, physiology, and Cd accumulation efficiency of two widely recognized poplar species, namely Populus deltoides and P. × canadensis, under Cd contamination (1 mg kg-1) in acid and alkaline purple soils. The objective was to determine which poplar species is best suited for remediating different soil types. Our findings are as follows: (1) the total biomass of both poplars remained largely unaffected by Cd pollution in both soil types. Notably, under Cd pollution, the total biomass of P. deltoides in acid purple soil was 1.53 times greater than that in alkaline purple soil. (2) Cd pollution did not significantly induce oxidative damage in the leaves of either poplar species in both soil types. However, in acid purple soil, Cd contamination led to a 21% increase in NO3- concentration and a 44% increase in NH4+ concentration in P. × canadensis leaves, whereas in alkaline purple soil, it led to a 59% increase in NH4+ concentration in P. deltoides leaves. (3) Cd concentrations in all root orders of P. × canadensis were significantly higher than those in P. deltoides, especially in the first three root orders, under alkaline purple soil. The total Cd accumulation by P. × canadensis in Cd-polluted alkaline purple soil was 2.18 times higher than that in Cd-polluted acid purple soil, a difference not observed in P. deltoides. (4) redundancy analysis indicated that the sequestration effect of higher soil organic matter on Cd availability in acid purple soil was more pronounced than the release effects caused by lower pH. In conclusion, P. × canadensis is better suited for remediating alkaline purple soil due to its higher capacity for Cd uptake, while P. deltoides is more suitable for remediating Cd-contaminated acid purple soil due to its better growth conditions and greater Cd enrichment capability.
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Populus , Contaminantes del Suelo , Cadmio/análisis , Suelo , Contaminantes del Suelo/análisis , Biodegradación AmbientalRESUMEN
Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.
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Leptina , Osificación Heterotópica , Animales , Ratones , Leptina/genética , Ligandos , Ratones Endogámicos C57BL , Osteogénesis , Receptores de Leptina/genética , Receptores de Leptina/metabolismoRESUMEN
Objective: To investigate the relationship of low T3 syndrome with disease severity in patients with COVID-19. Methods: The clinical data of 145 patients with COVID-19 were retrospectively collected, and patients were divided into a low T3 group and a normal T3 group. Logistic regression models were used to assess predictive performance of FT3. Receiver operating characteristic (ROC) analysis was used to evaluate the use of low T3 syndrome in predicting critical disease. Kaplan-Meier analysis was used to analyze the impact of low T3 syndrome on mortality. Results: The prevalence of low T3 level among COVID-19 patients was 34.48%. The low T3 group was older, and had lower levels of hemoglobin, lymphocytes, prealbumin, and albumin, but higher levels of white blood cells, neutrophils, CRP, ESR, and D-dimer (all p<0.05). The low T3 group had greater prevalences of critical disease and mortality (all p <0.05). Multivariate logistic regression analysis showed that the Lymphocytes, free T3 (FT3), and D-dimer were independent risk factors for disease severity in patients with COVID-19. ROC analysis showed that FT3, lymphocyte count, and D-dimer, and all three parameters together provided reliable predictions of critical disease. Kaplan-Meier analysis showed the low T3 group had increased mortality (p<0.001). Six patients in the low T3 group and one patient in the normal T3 group died. All 42 patients whose T3 levels were measured after recovery had normal levels after discharge. Conclusion: Patients with COVID-19 may have transient low T3 syndrome at admission, and this may be useful for predicting critical illness.
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Chromothripsis is a catastrophic event of chromosomal instability that involves intensive fragmentation and rearrangements within localized chromosomal regions. However, its cause remains unclear. Here, we show that reduction and inactivation of Ran GTPase-activating protein 1 (RanGAP1) commonly occur in human osteosarcoma, which is associated with a high rate of chromothripsis. In rapidly expanding mouse osteoprogenitors, RanGAP1 deficiency causes chromothripsis in chr1q, instant inactivation of Rb1 and degradation of p53, consequent failure in DNA damage repair, and ultrafast osteosarcoma tumorigenesis. During mitosis, RanGAP1 anchors to the kinetochore, where it recruits PP1-γ to counteract the activity of the spindle-assembly checkpoint (SAC) and prevents TOP2A degradation, thus safeguarding chromatid decatenation. Loss of RanGAP1 causes SAC hyperactivation and chromatid decatenation failure. These findings demonstrate that RanGAP1 maintains mitotic chromosome integrity and that RanGAP1 loss drives tumorigenesis through its direct effects on SAC and decatenation and secondary effects on DNA damage surveillance.
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Neoplasias Óseas , Cromotripsis , Osteosarcoma , Animales , Humanos , Ratones , Carcinogénesis , Inestabilidad Cromosómica , Proteínas Activadoras de GTPasa/metabolismo , Cinetocoros/metabolismo , MitosisRESUMEN
Primordial germ cells (PGCs) are the progenitor cells that give rise to sperm and eggs. Sinhcaf is a recently identified subunit of the Sin3 histone deacetylase complex (SIN3A-HDAC). Here, we provide evidence that Sinhcaf-dependent histone deacetylation is essential for germ plasm aggregation and primordial germ cell specification. Specifically, maternal-zygotic sinhcaf zebrafish mutants exhibit germ plasm aggregation defects, decreased PGC abundance and male-biased sex ratio, which can be rescued by re-expressing sinhcaf. Overexpression of sinhcaf results in excess PGCs and a female-biased sex ratio. Sinhcaf binds to the promoter region of kif26ab. Loss of sinhcaf epigenetically switches off kif26ab expression by increasing histone 3 acetylation in the promoter region. Injection of kif26ab mRNA could partially rescue the germ plasm aggregation defects in sinhcaf mutant embryos. Taken together, we demonstrate a role of Sinhcaf in germ plasm aggregation and PGC specialization that is mediated by regulating the histone acetylation status of the kif26ab promoter to activate its transcription. Our findings provide novel insights into the function and regulatory mechanisms of Sinhcaf-mediated histone deacetylation in PGC specification.
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Histonas , Pez Cebra , Animales , Femenino , Células Germinativas/metabolismo , Histonas/metabolismo , Masculino , ARN Mensajero/genética , Pez Cebra/genética , CigotoRESUMEN
OBJECTIVE: To investigate the changes in proinflammatory cytokines and chemokines, namely, C-C motif ligand (CCL) 2 and CCL7, in postmenopausal osteoporosis (PMOP) and to develop a new drug, bindarit (Bnd), for PMOP in an ovariectomized (OVX) mouse model. METHODS: Bone marrow macrophages (BMMs) from the femurs of five women with PMOP and five premenopausal women without osteoporosis were detected by RNA sequencing. BMMs from mice were differentiated into osteoclasts and treated with a synthetic inhibitor of CCL2 and CCL7, Bnd, or 17 beta estradiol (E2 ). Mouse BMMs were differentiated into osteoclasts with or without Bnd for 7 days and analyzed by RNA sequencing. Osteoblasts of mice were induced to undergo osteoblastogenesis and treated with Bnd. OVX mice were treated with E2 or Bnd after surgery. The protein and mRNA expression of CCL2 and CCL7 was detected using immunostaining and qPCR, respectively, in OVX and aged mice and in cells cultured in vitro. Osteoclast formation was detected using a tartrate-resistant acid phosphatase (TRAP) assay in vitro and in vivo. Alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) were detected using immunostaining to evaluate osteogenesis. Microcomputed tomography was conducted to analyze trabecular bone parameters, the structure model index, bone mineral density and other variables. Nuclear factor-κB (NF-κB) signaling pathway-related protein phosphorylation of IKKα/ß (p-IKKα/ß) and p-NFκB p65 was examined using western blotting. RESULTS: CCL2, CCL7 and their receptor of C-C chemokine receptor-2 (CCR2), and the NF-κB signaling pathway, were significantly increased in women with PMOP. CCL2 and CCL7 protein and mRNA expression was increased in OVX mice and aged female mice, but the increases were attenuated by E2 and Bnd. E2 and Bnd effectively inhibited osteoclastogenesis and the protein expression of CCL2 and CCL7 both in vitro and in vivo and reduced bone loss in OVX mice. Bnd did not affect the mineralization of osteoblasts directly in vitro but reduced bone turnover in vivo. p-IKKα/ß and p-NFκB p65 levels were increased in BMMs of mice after differentiation into osteoclasts but were significantly decreased by Bnd. CONCLUSION: The proinflammatory cytokines and chemokines CCL2, CCL7 and CCR2 were correlated with PMOP. Bnd attenuated the increases in CCL2 and CCL7 levels to affect osteoporosis in OVX mice via the NFκB signaling pathway. Thus, Bnd may be useful as a new therapeutic for the prevention of PMOP.
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Enfermedades Óseas Metabólicas , Resorción Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Animales , Diferenciación Celular , Quimiocina CCL2 , Quimiocina CCL7 , Citocinas/metabolismo , Femenino , Humanos , Quinasa I-kappa B/metabolismo , Quinasa I-kappa B/farmacología , Indazoles , Ratones , FN-kappa B/metabolismo , Osteoclastos , Osteogénesis , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Ovariectomía , Propionatos , ARN Mensajero/metabolismo , Transducción de Señal , Microtomografía por Rayos XRESUMEN
At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.
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COVID-19/epidemiología , Brotes de Enfermedades , Neumonía/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , SARS-CoV-2/aislamiento & purificación , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Líquido del Lavado Bronquioalveolar/microbiología , COVID-19/virología , China/epidemiología , Estudios de Cohortes , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Metagenómica , Persona de Mediana Edad , Filogenia , Neumonía/microbiología , Infecciones del Sistema Respiratorio/microbiología , Adulto JovenRESUMEN
How stoichiometry in different ecosystem components responds to long-term nitrogen (N) addition is crucial for understanding within-ecosystem biogeochemistry cycling processes in the context of global change. To explore the effects of long-term N addition on nutrient stoichiometry in soil and plant components in forest ecosystem, a 10-year N addition experiment using ammonium nitrate (NH4NO3) was conducted in a bamboo forest in the Rainy Zone of West China, where the background N deposition is the highest in the world. Four N treatment levels (+0, +50, +150, +300 kg N ha-1 yr-1) (CK, LN, MN, HN) were applied monthly since November 2007, and then, the C:N:P stoichiometry of soil, microbial biomass, and enzymes in rhizosphere soil and bulk soil, and plant organs were measured. N addition decreased the stoichiometry of C:N:P of soil, microbial biomass, and enzymes. Soil C:N:P change under N addition treatments was stronger in bulk soil, while C:N:P changes for microbial biomass and enzyme activity were significant in rhizosphere soil. N addition significantly decreased TOC in bulk soil. Changes in MBC:MBN:MBP in rhizosphere and bulk soil were mainly caused by MBN and MBP, and MBP performance was consistent with that of AP. The main variable leading to the change of enzyme C:N:P in rhizosphere soil was BG and AP, and in bulk soil was LAP + NAG activity. Plant root C:P and N:P increased with N addition, while those for leaves and twigs did not. N addition significantly reduced the pH of both rhizosphere and bulk soils. These results suggest that the stoichiometry responses of rhizosphere and bulk soils were different due to the influence of plant roots. Soil acidification, enhanced aluminum toxicity potential, decreased root biomass and enhanced microbial P limitation caused by N addition were the important mechanisms that promoted stoichiometry changes in this ecosystem. Under the chronic input of N deposition, the stoichiometry between plant and soil evolved in different directions, which may lead to the decoupling of plants from soils.
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Nitrógeno , Suelo , Biomasa , Carbono/análisis , China , Ecosistema , Bosques , Nitrógeno/análisis , Rizosfera , Microbiología del SueloRESUMEN
Lysosomes are the recycling center and nutrient signaling hub of the cell. Here, we show that lysosomes also control mesenchymal stem cell (MSC) differentiation by proteomic reprogramming. The chaperone-mediated autophagy (CMA) lysosome subgroup promotes osteogenesis, while suppressing adipogenesis, by selectively removing osteogenesis-deterring factors, especially master transcriptional factors, such as adipogenic TLE3, ZNF423, and chondrogenic SOX9. The activity of the CMA-committed lysosomes in MSCs are controlled by Van-Gogh-like 2 (Vangl2) at lysosomes. Vangl2 directly binds to lysosome-associated membrane protein 2A (LAMP-2A) and targets it for degradation. MSC-specific Vangl2 ablation in mice increases LAMP-2A expression and CMA-lysosome numbers, promoting bone formation while reducing marrow fat. The Vangl2:LAMP-2A ratio in MSCs correlates inversely with the capacity of the cells for osteoblastic differentiation in humans and mice. These findings demonstrate a critical role for lysosomes in MSC lineage acquisition and establish Vangl2-LAMP-2A signaling as a critical control mechanism.
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Diferenciación Celular , Autofagia Mediada por Chaperones , Condrogénesis , Lisosomas/metabolismo , Células Madre Mesenquimatosas/citología , Proteínas del Tejido Nervioso/fisiología , Osteogénesis , Adipogénesis , Anciano , Animales , Femenino , Humanos , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C3H , Ratones Noqueados , Chaperonas Moleculares , Osteoporosis/patología , Osteoporosis/terapiaRESUMEN
The effects of cadmium stress on the growth and physiological characteristics of Sassafras tzumu Hemsl. were studied in pot experiments. Five Cd levels were tested [CT(Control Treatment) : 0 mg/kg, Cd5: 5 mg/kg, Cd20: 20 mg/kg, Cd50: 50 mg/kg, and Cd100: 100 mg/kg]. The growth and physiological characteristics of the sassafras seedlings in each level were measured. The results showed that soil Cd had negative influences on sassafras growth and reduced the net growth of plant height and the biomass of leaf, branch and root. Significant reductions were recorded in root biomass by 18.18%(Cd5), 27.35%(Cd20), 27.57%(Cd50) and 28.95%(Cd100). The contents of hydrogen peroxide decreased first then increased while malondialdehyde showed the opposite trend with increasing cadmium concentration. Decreases were found in hydrogen peroxide contents by 10.96%(Cd5), 11.82%(Cd20) and 7.02%(Cd50); increases were found in malondialdehyde contents by 15.47%(Cd5), 16.07%(Cd20) and 7.85%(Cd50), indicating that cadmium stress had a certain effect on the peroxidation of the inner cell membranes in the seedlings that resulted in damage to the cell membrane structure. Superoxide dismutase activity decreased among treatments by 17.05%(Cd5), 10,68%(Cd20), 20.85%(Cd50) and 8.91%(Cd100), while peroxidase activity increased steadily with increasing cadmium concentration; these results suggest that peroxidase is likely the main protective enzyme involved in the reactive oxygen removal system in sassafras seedlings. Upward trends were observed in proline content by 90.76%(Cd5), 74.36%(Cd20), 99.73%(Cd50) and 126.01%(Cd100). The increase in proline content with increasing cadmium concentration indicated that cadmium stress induced proline synthesis to resist osmotic stress in the seedlings. Compared to that in CT, the soluble sugar content declined under the different treatments by 32.84%(Cd5), 5.85%(Cd20), 25.55%(Cd50) and 38.69%(Cd100). Increases were observed in the soluble protein content by 2.34%(Cd5), 21.36%(Cd20), 53.15%(Cd50) and 24.22%(Cd100). At different levels of cadmium stress, the chlorophyll content in the seedlings first increased and then decreased, and it was higher in the Cd5 and Cd20 treatments than that in the CT treatment. These results reflected that cadmium had photosynthesis-promoting effects at low concentrations and photosynthesis-suppressing effects at high concentrations. The photosynthetic gas exchange parameters and photosynthetic light-response parameters showed downward trends with increasing cadmium concentration compared with those in CT; these results reflected the negative effects of cadmium stress on photosynthesis in sassafras seedlings.
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Cadmio/toxicidad , Fotosíntesis/efectos de los fármacos , Sassafras/efectos de los fármacos , Plantones/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Clorofila/análisis , Clorofila/metabolismo , Presión Osmótica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Peroxidasas/análisis , Peroxidasas/metabolismo , Proteínas de Plantas/análisis , Proteínas de Plantas/metabolismo , Prolina/análisis , Prolina/biosíntesis , Especies Reactivas de Oxígeno/metabolismo , Sassafras/química , Sassafras/enzimología , Sassafras/crecimiento & desarrollo , Plantones/química , Plantones/enzimología , Plantones/crecimiento & desarrollo , Suelo/química , Superóxido Dismutasa/metabolismoRESUMEN
Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.
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Advanced oxidative protein products (AOPPs) are novel uremic toxins whose concentrations continuously increases in patients with chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) of tubular cells is the main mechanism underlying CKD pathogenesis. Studies have shown that AOPPs can induce EMT and promote renal fibrosis. However, the mechanism through which AOPPs induce tubular cell-EMT is poorly understood. In this study, we aimed to clarify the mechanisms underlying AOPP-induced EMT in human kidney proximal tubular (HKC-8) epithelial cells. Small molecule inhibitor, CRISPR-Cas9 knockout technology, siRNA knockdown technology, western blot, and reverse transcription-quantitative polymerase chain reaction were applied to investigate the mechanisms underlying AOPP-induced EMT in HKC-8 cells. AOPP treatment was found to significantly induce EMT, as evidenced by increased α-smooth muscle actin (α-SMA) and decreased E-cadherin levels, and upregulated Wnt1, ß-catenin, Tcf4, and Gsk-3ß expression. Conversely, blockade of Wnt/ß-catenin signaling using small molecule inhibitor ICG-001 hindered AOPP-induced EMT. Moreover, knockout of receptor of advanced glycation end-products (RAGE) reversed these aforementioned effects, whereas AGE receptor 1 (AGER1)-specific siRNA transfection enhanced them. Taken together, these data suggested that AOPPs could induce HKC-8 cell EMT by activating the RAGE/Wnt/ß-catenin signaling pathway and AGER1 could restore EMT by antagonizing the role of RAGE. These results may provide a new theoretical basis for EMT and help identify new therapeutic targets for suppressing CKD progression.
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Células Epiteliales/patología , Transición Epitelial-Mesenquimal , Silenciador del Gen , Túbulos Renales Proximales/patología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Biomarcadores/metabolismo , Línea Celular , Supervivencia Celular , Células Epiteliales/metabolismo , Humanos , Oxidación-Reducción , Vía de Señalización WntRESUMEN
BACKGROUND: Elderly patients with coronary heart disease often suffer adverse psychological reactions, such as anxiety and depression. The dual-track interactive nursing model is a nursing intervention aimed to provide specific and community nursing. For patients with chronic diseases, this model can improve the patients' self-management and rehabilitation. The effect of this model on the mental health of patients with chronic diseases has been unanimously recognized by researchers. In this study, a dual-track interactive nursing model intervention was conducted on the anxiety and depression in elderly patients with coronary heart disease to verify the psychological effect of the model. SUBJECTS AND METHODS: From June 2018 to June 2019, 136 elderly patients with coronary heart disease (mean age of 63.5±8.26 years) from three communities in Changsha, Hunan Province, China were selected as subjects. A total of 53 and 50 patients were identified in the intervention and the control groups, respectively. The control group underwent routine longitudinal referral, whereas the intervention group was subjected to a two-track interactive nursing model intervention. The Short Form-36 Health Survey (SF-36) and related questionnaires were used to monitor and compare the two groups before and after the intervention and employed for scoring and comparative analysis. RESULTS: After the intervention, the mental health scores of the intervention group in total score, somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, and paranoia are significantly lower than those of the control group (P<0.05). The intervention group has scored significantly higher in coping style but significantly lower in negative coping than the control group (P<0.05). CONCLUSIONS: The application of the dual-track interactive nursing model intervention in the management of patients with coronary heart disease can improve the self-management and the mental health of patients with coronary heart disease.
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Trastornos de Ansiedad , Enfermedad Coronaria , Depresión , Anciano , Ansiedad , China , Enfermedad Coronaria/psicología , Humanos , Persona de Mediana EdadRESUMEN
In this work, ethyl acetate (EA) and trichloromethane (TR) extracts were extracted from Phoebe zhennan wood residues and the extracts were then applied to the preparation of UV shielding films (UV-SF). The results revealed that substances including olefins, phenols and alcohols were found in both EA and TR extracts, accounting for about 45% of all the detected substances. The two extracts had similar thermal stability and both had strong UV shielding ability. When the relative percentage of the extract is 1 wt% in solution, the extract solution almost blocked 100% of the UV-B (280-315 nm), and UV-A (315-400 nm). Two kinds of UV-SF were successfully prepared by adding the two extracts into polylactic acid (PLA) matrix. The UV-SF with the addition of 24 wt% of the extractive blocked 100% of the UV-B (280-315 nm) and more than 80% of the UV-A (315-400 nm). Moreover, the UV shielding performance of the UV-SF was still stable even after strong UV irradiation. Though the addition of extracts could somewhat decrease the thermal stability of the film, its effect on the end-use of the film was ignorable. EA extracts had less effect on the tensile properties of the films than TR extracts as the content of the extract reached 18%. The results of this study could provide fundamental information on the potential utilization of the extracts from Phoebe zhennan wood residues on the preparation of biobased UV shielding materials.
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Acetatos/química , Cloroformo/química , Extractos Vegetales/química , Rayos Ultravioleta , Madera/químicaRESUMEN
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoimmune-mediated platelet destruction and impaired platelet production, which can lead to an increased risk of bleeding. The clinical management of ITP currently remains a challenge for hematologists. We explored the role of interleukin-9 (IL-9) in the treatment of CD41-induced ITP, and investigated its underlying mechanisms in a CD41-induced ITP mouse model. IL-9 treatment increased the numbers of mature megakaryocytes (CD41+CD42d+) and CD41+Sca-1+ cells in the bone marrow in these model mice, while IL-9 receptor (IL-9R) small interfering RNA (siRNA) inhibited the process. Moreover, phosphorylated signal transducer and activator of transcription 5 (STAT5), as a downstream molecule of IL-9R, was increased after IL-9 treatment. We next investigated the source of IL-9 in bone marrow, osteoblasts produced the highest level of IL-9. These results confirmed that IL-9 could prevent CD41-induced ITP in BALB/c mice by regulating osteoblasts and activating IL-9R/STAT5 signaling in megakaryocytes, thus providing further evidence for IL-9 as a promising therapeutic agent for the treatment of ITP.