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BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.
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Melanoma Experimental , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Fator de Transcrição STAT3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Humanos , Furanos/farmacologia , Simulação de Acoplamento Molecular , Sobrevivência Celular/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Autofagia/efeitos dos fármacos , SesquiterpenosRESUMO
We report herein the development of palladium-catalyzed deacylative deuteration of arylketone oxime ethers. This protocol features excellent functional group tolerance, heterocyclic compatibility, and high deuterium incorporation levels. Regioselective deuteration of some biologically important drugs and natural products are showcased via Friedel-Crafts acylation and subsequent deacylative deuteration. Vicinal meta-C-H bond functionalization (including fluorination, arylation, and alkylation) and para-C-H bond deuteration of electro-rich arenes are realized by using the ketone as both directing group and leaving group, which is distinct from aryl halide in conventional dehalogenative deuteration.
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Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.
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Neoplasias Colorretais , Saponinas , Animais , Apoptose , Autofagia , Neoplasias Colorretais/patologia , Humanos , Camundongos , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Saponinas/farmacologia , Saponinas/uso terapêutico , Esteroides , Serina-Treonina Quinases TOR/metabolismoRESUMO
Dispersion is one of the most important issues in see-through near eye displays with waveguide technology. In particular, the nanophotonics design is challenging but demanding. In this paper, we propose a design method for a multilayer achromatic metasurface structure for near eye display application by a physics-driven generative neural network. Two in-coupling metagratings under different projector illuminations are presented and numerically verified with the absolute diffraction efficiency over 89%. A beam splitter, which provides a balance between compactness and visual comfort in a single-projector-binocular display, is also designed. Finally, we apply this method to an out-coupling metasurface with the capability of enlarging the visible region by threefold.
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In this study, 17 Y-chromosomal short tandem repeats (Y-STRs) were analyzed in 1026 male individuals of Han populations in Changchun City, Jilin Province, Northeast China. The haplotype diversity is 0.99892. The Changchun Han population is close to most Han populations and different from most other minority populations of China. Additionally, the Changchun Han show more affiliations with Han populations in North and Northeast China. These data provide a reference for the Y-STR database in Jilin Province, and they may be valuable for population genetic analysis.
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Cromossomos Humanos Y , Genética Populacional , Repetições de Microssatélites , China , Etnicidade , Frequência do Gene , Haplótipos , Humanos , Masculino , Polimorfismo GenéticoRESUMO
Background: Induction chemotherapy (ICT) has become an initial treatment for head and neck squamous cell carcinoma (HNSCC). However, myelosuppression, an unavoidable side effect of ICT, significantly impacts follow-up treatment and prognosis. The main objective of this study is to identify the risk factors and predictors of myelosuppression and its different severity after ICT for ICT. Methods: We retrospectively reviewed medical records of 102 patients with hypopharyngeal cancer or oropharyngeal cancer who received initial ICT from 2013 to 2022. Univariate and multivariate logistic regression analyses were performed to identify risk factors for myelosuppression. Receiver-operating characteristic (ROC) curves were generated using the results of multiple logistic regression analysis to identify data with the highest sensitivity and lowest false-negative rate. Results: Pretreatment lymphocyte count (PLC) and the pretreatment platelet count (PPC) were identified as independent risk factors of myelosuppression (P < .05). Pretreatment hemoglobin count (PHC) was an independent risk factor for predicting myelosuppression in patients with grades III to IV disease. Patients with myelosuppression after ICT are more sensitive to chemotherapy. Conclusions: The PLC and PPC predicted myelosuppression in patients with HNSCC-administered ICT, and the PHC predicted grades III to IV myelosuppression. Myelosuppressed patients were more chemosensitive after ICT.
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ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) poses a growing challenge to global health efforts. The 5-year survival rate of HCC patients is still dismal. A traditional prescription Qi-Wei-Wan (QWW) comprising Astragali Radix and Schisandra chinensis Fructus has traditionally been used for HCC treatment according to traditional Chinese medicine theory, but the pharmacological basis is not clear. AIM OF THE STUDY: This study aims to investigate the anti-HCC effects of an ethanolic extract of QWW (hereafter, QWWE) and the mechanism of action. MATERIALS AND METHODS: An UPLC-Q-TOF-MS/MS method was developed to control the quality of QWWE. Two human HCC cell lines (HCCLM3 and HepG2) and a HCCLM3 xenograft mouse model were employed to investigate the anti-HCC effects of QWWE. The anti-proliferative effect of QWWE in vitro was determined by MTT, colony formation and EdU staining assays. Apoptosis and protein levels were examined by flow cytometry and Western blotting, respectively. Nuclear presence of signal transducer and activator of transcription 3 (STAT3) was examined by immunostaining. Transient transfection of pEGFP-LC3 and STAT3C plasmids was performed to assess autophagy and determine the involvement of STAT3 signaling in QWWE's anti-HCC effects, respectively. RESULTS: We found that QWWE inhibited the proliferation of and triggered apoptosis in HCC cells. Mechanistically, QWWE inhibited the activation of SRC and STAT3 at Tyr416 and Tyr705, respectively; inhibited the nuclear translocation of STAT3; lowered Bcl-2 protein levels, while increased Bax protein levels in HCC cells. Over-activating STAT3 attenuated the cytotoxic and apoptotic effects of QWWE in HCC cells. Moreover, QWWE induced autophagy in HCC cells by inhibiting mTOR signaling. Blocking autophagy with autophagy inhibitors (3-methyladenine and chloroquine) enhanced the cytotoxicity, apoptotic effect and the inhibitory effect on STAT3 activation of QWWE. Intragastric administration of QWWE at 10 mg/kg and 20 mg/kg potently repressed tumor growth and inhibited STAT3 and mTOR signaling in tumor tissues, but did not significantly affect mouse body weight. CONCLUSION: QWWE exhibited potent anti-HCC effects. Inhibiting the STAT3 signaling pathway is involved in QWWE-mediated apoptosis, while blocking mTOR signaling contributes to QWWE-mediated autophagy induction. Blockade of autophagy enhanced the anti-HCC effects of QWWE, indicating that the combination of an autophagy inhibitor and QWWE might be a promising therapeutic strategy for HCC management. Our findings provide pharmacological justifications for the traditional use of QWW in treating HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Schisandra , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Espectrometria de Massas em Tandem , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Proliferação de CélulasRESUMO
The Spirometra mansoni is a neglect medical tapeworm, its plerocercoid larvae can parasitize in humans and animals, causing sparganosis. In this study, 17 new members of the glutathione transferase (GST) family were sequenced and characterized in S. mansoni. Clustering analysis displayed the categorization of SmGSTs into two main clades. RT-qPCR illustrated that 7 GST genes were highly expressed in the plerocercoid stage while 8 GSTs were highly expressed in the adult. rSmGST has the typical C- and N-terminal double domains of glutathione transferase. Immunolocalization revealed that natural SmGST is mainly located in the epidermis and parenchyma of plerocercoid, and in the epidermis, parenchyma, uterus and egg shell of adult worm. The optimum activity for rSmGST was found to be pH 6.5 and 25°C. The evolutionary tree showed a high level of diversity of cestodes GSTs. SmGSTs contained both conserved family members and members in the process of further diversification. The findings in this study will lay a foundation to better explore the underlying mechanisms of GSTs involved in Spirometra tapeworms.
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BACKGROUND: In China, the plerocercoid of the cestode Spirometra mansoni is the main causative agent of human and animal sparganosis. However, the population genetic structure of this parasite remains unclear. In this study, we genotyped S. mansoni isolates with the aim to improve current knowledge on the evolution and population diversity of this cestode. METHODS: We first screened 34 perfect simple sequence repeats (SSRs) using all available omic data and then constructed target sequencing technology (Target SSR-seq) based on the Illumina NovaSeq platform. Next, a series of STRUCTURE. clustering, principal component, analysis of molecular variance and TreeMix analyses were performed on 362 worm samples isolated from 12 different hosts in 16 geographical populations of China to identify the genetic structure. RESULTS: A total of 170 alleles were detected. The whole population could be organized and was found to be derived from the admixture of two ancestral clusters. TreeMix analysis hinted that possible gene flow occurred from Guizhou (GZ) to Sichuan (SC), SC to Jaingxi (JX), SC to Hubei (HB), GZ to Yunnan (YN) and GZ to Jiangsu (JS). Both neighbor-joining clustering and principal coordinate analysis showed that isolates from intermediate hosts tend to cluster together, while parasites from definitive hosts revealed greater genetic differences. Generally, a S. mansoni population was observed to harbor high genetic diversity, moderate genetic differentiation and a little genetic exchange among geographical populations. CONCLUSIONS: A Target SSR-seq genotyping method was successfully developed, and an in-depth view of genetic diversity and genetic relationship will have important implications for the prevention and control of sparganosis.
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Esparganose , Spirometra , Animais , Humanos , Spirometra/genética , China/epidemiologia , Filogenia , Genótipo , Repetições de Microssatélites , Variação GenéticaRESUMO
BACKGROUND: Pancreatic cancer has been characterized by poor prognosis, early metastasis and dissatisfactory treatment outcome. The high basal level of autophagy in tumor cells leads to chemoresistance and tumor progression. Thus, it is imminent to explore novel effective chemotherapeutic adjuvants to increase patients' survival rate. Isoliquiritigenin (ISL) is a bioactive flavonoid obtained from the Traditional Chinese herbal medicine Glycyrrhiza glabra, and it possesses a broad range of pharmacological effects. In this study, the anti-cancer effect of ISL in pancreatic cancer treatment and the underlying mechanism are investigated. METHODS: MTT assay, colony formation and EdU analysis were performed to explore the growth inhibition of ISL on pancreatic cancer cells. Apoptosis were analyzed using TUNEL and flow cytometry. The formations of autophagosomes were analyzed by immunofluorescence microscopy and transmission electron microscopy. RFP-GFP-LC3B probe was applied to detect the autophagy flux. To assess the structural interaction of ISL with p38 protein, molecular docking assays were performed. The molecular mechanism was elucidated by using western immunoblotting. Subsequently, the inhibition of ISL on tumor growth was determined in vivo using pancreatic tumor mice model. RESULTS: ISL inhibited pancreatic cancer cell growth and induced apoptosis, both in vitro and in vivo. ISL caused accumulation of autophagosome through blockade of late stage autophagic flux. Moreover, autophagy inducer rapamycin enhanced ISL-evoked cell growth inhibition and promoted apoptosis, while inhibition of autophagosome formation by siAtg5 attenuated ISL-induced apoptosis. It is remarkable that ISL synergistically sensitized the cytotoxic effect of gemcitabine and 5-fluorouracil on pancreatic cancer cells as both drugs induced autophagy. Molecular docking analysis has indicated that ISL acted by direct targeting of p38 MAPK, which was confirmed by ISL-induced phosphorylation of p38. The autophagy flux induced by p38 inhibitor SB203580 was blocked by ISL, with further increasing toxicity of ISL in pancreatic cancer cells. CONCLUSION: The results have revealed that ISL inhibited pancreatic cancer progression by blockade of autophagy through p38 MAPK signaling.
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Chalconas , Medicamentos de Ervas Chinesas , Neoplasias Pancreáticas , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Chalconas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fluoruracila/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Neoplasias Pancreáticas/tratamento farmacológico , Sirolimo/farmacologia , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Background: PD-1/PD-L1 blockade is a promising immunotherapeutic strategy with the potential to improve the outcomes of various cancers. However, there is a critically unmet need for effective biomarkers of response to PD-1/PD-L1 blockade. Materials and methods: Potential biomarkers of response to PD-1/PD-L1 blockade were obtained from the Cancer Treatment Response gene signature Database (CTR-DB). A comprehensive pan-cancer analysis was done on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Correlations between gene expression and infiltration by immune cells were assessed using TIMER, EPIC, MCPcounter, xCell, CIBERSORT, and quanTIseq. Immunophenoscore (IPS) was used to assess the potential application of the biomarkers to all TCGA tumors. Results: Analysis of CTR-DB data identified CD69 and SBK1 as potential biomarkers of response to PD-1/PD-L1 blockade. Correlation analysis revealed that in various TCGA cancer datasets, CD69 expression level correlated positively with most immune checkpoints and tumor-infiltrating immune cells, while SBK1 expression level correlated negatively with infiltrating immune cells. IPS analysis demonstrated the ability of CD69 and SBK1 to predict PD-1/PD-L1 blockade responses in various cancers. Conclusion: CD69 and SBK1 are potential predictors of response to cancer immunotherapy using PD-1/PD-L1 blockade. These biomarkers may guide treatment decisions, leading to precise treatment and minimizing the waste of medical resources.
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Neoplasias Pulmonares , Melanoma , Antígeno B7-H1/genética , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/patologia , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1RESUMO
Pancreatic cancer is amongst the most lethal malignancies, while its poor prognosis could be associated with promotion of autophagy and the tumor immune microenvironment. Studies have confirmed the pro-tumorigenic nature of the cathelicidin family of peptide LL-37 in several types of cancer. However, at higher doses, LL-37 exerts significant cytotoxicity against gastrointestinal cancer cells. In our study, we investigated the anti-tumorigenic potential of LL-37 in pancreatic cancer and the underlying mechanisms. Our results have shown that LL-37 inhibited the growth of pancreatic cancer both in vitro and in vivo. Mechanistic studies have demonstrated that LL-37 induced DNA damage and cell cycle arrest through induction of reactive oxygen species (ROS). Further study indicates that LL-37 suppressed autophagy in pancreatic cancer cells through activation of mTOR signaling, leading to more accumulation of ROS production and induction of mitochondrial dysfunctions. With combined treatment of LL-37 with the mTOR inhibitor rapamycin, LL-37-induced ROS production and cancer cell growth inhibition were attenuated. Subsequent in vivo study has shown that LL-37 downregulated the immunosuppressive myeloid-derived suppressor cells and M2 macrophages while upregulated the anti-cancer effectors CD8+ and CD4+ T cells in the tumor microenvironment. By using an in vitro co-culture system, it was shown that promotion of M2 macrophage polarization would be suppressed by LL-37 with inhibition of autophagy, which possessed significant negative impact on cancer growth. Taken together, our findings implicate that LL-37 could attenuate the development of pancreatic cancer by suppressing autophagy and reprogramming of the tumor immune microenvironment.
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The plerocercoid larvae of the tapeworm Spirometra erinaceieuropaei can parasitize humans and animals and cause serious parasitic zoonosis. However, our knowledge of the developmental process of S. erinaceieuropaei is still inadequate. To better characterize differential and specific genes and pathways associated with parasite development, a comparative transcriptomic analysis of the plerocercoid stage and the adult stage was performed using RNA-seq and de novo analysis. Approximately 13,659 differentially expressed genes (DEGs) were identified in plerocercoids versus adults, of which 6455 DEGs were upregulated and 7204 were downregulated. DEGs involved in parasite immunoevasion were more active in plerocercoid larvae than in adults, while DEGs associated with metabolic activity were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses revealed that most DEGs involved in protein phosphorylation/dephosphorylation and the Wnt signalling pathway were much more active in plerocercoid larvae. The molecular functions of upregulated unigenes in adults were mainly enriched for metabolic activities. qPCR validated that the expression levels of 10 selected DEGs were consistent with those in RNA-seq, confirming the accuracy of the RNA-seq results. Our results contributed to increasing the knowledge on the S. erinaceieuropaei gene repertoire and expression profile and also provide valuable resources for functional studies on the molecular mechanisms of S. erinaceieuropaei.
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Infecções por Cestoides , Esparganose , Spirometra , Animais , Perfilação da Expressão Gênica , Esparganose/parasitologia , Spirometra/genética , Transcriptoma , ZoonosesRESUMO
Eight rice varieties suitable for local cultivation were selected and field tests were carried out to compare the accumulation, absorption, and transport characteristics of Cd. The rice varieties with low Cd accumulation were screened, and the factors affecting the accumulation degree and stability of rice were analyzed. The results showed that:â According to the comprehensive accumulation index(PN) evaluation method, the rice varieties with low PN ability for Cd were selected as follows:Chuanyou 3203, Chuanyou 6203, Dejing 6, and Shenyou 17. â¡Considering the Cd content and yield of rice, Chuanyou 3203 and Chuanyou 6203 are suitable for planting in this region, which guarantees a safe Cd content in and high yield of rice. â¢The contents of Cd in Chuanyou 3203 and Chuanyou 6203 were significantly lower than those of other rice varieties and stable under different pH and total Cd ranges and soil conditions. â£The difference between rice varieties had a significant effect on rice enrichment ability, but little effect on translocation from stem to leaf. The low enrichment coefficient of Chuanyou 3203 and Chuanyou 6203, combined with low translocation, demonstrated the low Cd enrichment capacity of rice. â¤Correlation analysis showed that the Cd content was most affected by the enrichment coefficient of rice, and least affected by the total Cd content of rhizosphere soil.
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Oryza , Poluentes do Solo , Cádmio/análise , Rizosfera , Solo , Poluentes do Solo/análiseRESUMO
BACKGROUND: The effect of urolithiasis on pregnancy-related outcomes remains unknown. The aim of this study was to determine the risk of adverse maternal and neonatal outcomes. METHODS: We searched PubMed, Embase, and the Cochrane Library through December 2020 for studies reporting on adverse maternal and neonatal outcomes in patients with urolithiasis. Risk ratios (ORs) with 95% confidence intervals (CIs) were calculated for these outcomes in pregnant mothers with urolithiasis and compared to healthy controls. RESULTS: Eight studies comprising 26,577 mothers with urolithiasis were included in our analysis. Preterm birth (OR = 1.63; 95% CI 1.37-1.95, p < 0.001) or very preterm birth risk (OR = 1.49, 95% CI 1.06-2.11, p = 0.02) was more common in patients with urolithiasis compared to healthy controls. Mothers with urolithiasis had an increased incidence of preeclampsia (OR = 1.75, 95% CI 1.33-2.3, p < 0.001), hypertension (OR = 2.97, 95% CI 1.31-6.71, p = 0.009), caesarean section (OR 1.31, 95% CI 1.11-1.55, p = 0.001), and gestational diabetes mellitus (OR 1.84, 95% CI 1.37-2.46, p < 0.001). CONCLUSION: Patients with urolithiasis may be at increased risk of developing adverse maternal or neonatal outcomes.
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Diabetes Gestacional , Nascimento Prematuro , Urolitíase , Cesárea , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Urolitíase/diagnóstico , Urolitíase/epidemiologiaRESUMO
Phytochelatins (PCs) can chelate heavy metal ions due to their large number of thiols and play an important role in heavy metal accumulation and detoxification. A. hypochondriacus K472, a cadmium (Cd) enriched plant, was selected as the research object. Six Cd treatment concentrations, namely 0 (CK), 10 (T1), 25 (T2), 50 (T3), 100 (T4), and 200 mg ·kg-1 (T5), were used to analyze the variation of PCs in different growth stages under different degrees of Cd stress and to explore the mechanism by which PCs chelate and detoxify Cd. The results showed that the plant height, root length, and biomass of K472 decreased significantly with increasing Cd concentration, and the range of decrease gradually became less pronounced with the growth and development of K472. K472 exhibited the maximum ability to enrich Cd during the middle vegetative growth period. The maximum concentration was 6695.35 mg, and the maximum bioconcentration factor was 6.3. In addition, with increasing Cd concentration, the Cd content of K472 roots, stems, and leaves was positively correlated with the concentration of PCs. PC3 had the strongest response to Cd stress in roots and stems, whereas PC2 responded to stress in leaves. For practical applications, harvesting K472 in the middle of vegetative growth is an optimal strategy for the remediation of Cd-contaminated soil.
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Amaranthus , Poluentes do Solo , Biodegradação Ambiental , Cádmio/análise , Cádmio/toxicidade , Fitoquelatinas , Raízes de Plantas/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidadeRESUMO
Huaganjian decoction (HGJD) was first recorded in the classic "Jing Yue Quan Shu" during the Ming dynasty, and it has been extensively applied in clinical practice to treat liver diseases for over 300 years in China. However, its bioactive constituents and relevant pharmacological mechanism are still unclear. In this study, a strategy integrating network analysis and metabolomics was applied to reveal mechanism of HGJD in treating cholestatic hepatic injury (CHI). Firstly, we observed the therapeutic effect of HGJD against CHI with an alpha-naphthylisothiocyanate (ANIT) induced CHI rat model. Then, we utilized UPLC-Q-Exactive MS/MS method to analyze the serum migrant compounds of HGJD in CHI rats. Based on these compounds, network analysis was conducted to screen for potential active components, and key signaling pathways interrelated to therapeutic effect of HGJD. Meanwhile, serum metabolomics was utilized to investigate the underlying metabolic mechanism of HGJD against CHI. Finally, the predicted key pathway was verified by western blot and biochemical analysis using rat liver tissue from in vivo efficacy experiment. Our results showed that HGJD significantly alleviated ANIT induced CHI. Totally, 31 compounds originated from HGJD have been identified in the serum sample. PI3K/Akt/Nrf2 signaling pathway related to GSH synthesis was demonstrated as one of the major pathways interrelated to therapeutic effect of HGJD against CHI. This research supplied a helpful strategy to determine the potential bioactive compounds and mechanism of traditional Chinese medicine.
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BACKGROUND: Necator americanus is one of the major etiological agents of human ancylostomiasis. Historically, the epidemiology of ancylostomiasis in Henan Province of central China and the molecular characteristics of N. americanus have been poorly understood. METHODS: In this study, we report a case of ancylostomiasis in Zhengzhou city of Henan Province. We also review the epidemiology of ancylostomiasis in Henan Province from 1949 to 2020. In addition, the complete mitochondrial (mt) genome of one clinical isolate is fully characterized using Illumina sequencing. All available mt genomes of hookworms in GenBank were included to reconstruct the phylogeny using both maximum likelihood (ML) and Bayesian inference (BI) methods. RESULTS: A total of three worms were collected from the patient. These worms were identified as N. americanus based on morphological characteristics as well as confirmed by genotyping with the barcoding gene cox1. Although ancylostomiasis cases have dropped substantially in recent years, hookworm infection is still a public health problem in underdeveloped areas and remote rural areas in Henan Province. The mt genome features of the N. americanus contained 12 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a major non-coding region. The nad1 gene showed high sequence variability among isolates, which is worth considering for future genetic studies of N. americanus. Phylogenetic analyses support the monophyly of hookworm isolates from different hosts and distinct geographical locations. CONCLUSIONS: The mt genome of N. americanus presented here will serve as a useful data set for studying population genetics and phylogenetic relationships of hookworms. Positive measures for preventing and controlling ancylostomiasis are required by both health services and individuals in Henan Province.
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Ancilostomíase/epidemiologia , Genoma Helmíntico , Técnicas de Diagnóstico Molecular , Necator americanus/genética , Necatoríase/diagnóstico , Necatoríase/epidemiologia , Idoso , Animais , China/epidemiologia , DNA de Helmintos/genética , Feminino , Humanos , Necator americanus/isolamento & purificaçãoRESUMO
PURPOSE: Human cases of thelaziasis caused by Thelazia callipaeda have increased in China in recent years. Although this species is of medical importance, our knowledge about the epidemiology of thelaziasis is still fragmentary. This study first reports a case of thelaziasis in central China. Then, the epidemiology of thelaziasis in China in the past 100 years (1917-2018) is reviewed. METHODS: A 5-year-old girl experienced discomfort in her left eye. Four thread-like worms were seen in the nasal upper eyelid of the left eye. The symptoms disappeared after these parasites were removed. In addition, we reviewed studies of Chinese human thelaziasis cited in articles or book chapters in all languages from inception to 31 Dec 2019. RESULTS: China is the nation with the most reports of thelaziasis (653 cases) in the world. More human cases were reported in central and eastern China than in other areas, and the majority of cases were from rural areas in poor socioeconomic settings. CONCLUSION: Special attention should be paid to this neglected disease in China. The use of a One Health approach is imperative for preventing eyeworm infections in humans.
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Infecções Oculares Parasitárias/diagnóstico , Infecções por Spirurida/diagnóstico , Infecções por Spirurida/epidemiologia , Thelazioidea/isolamento & purificação , Animais , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Thelazioidea/classificaçãoRESUMO
Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers (cathelin-related antimicrobial peptide (CRAMP), stathmin, elongation factor-1α (EF-1α), and chitinase) were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy (IgAN) progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS), there is no protein upregulation with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine) sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.