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Introduction: The liver is the only organ capable of full regeneration in mammals. However, the exact mechanism of gut microbiota and metabolites derived from them relating to liver regeneration has not been fully elucidated. Methods: To demonstrate how the gut-liver axis contributes to liver regeneration, using an LC-QTOF/MS-based metabolomics technique, we examine the gut microbiota-derived metabolites in the gut content of C57BL/6J mice at various points after 2/3 partial hepatectomy (PHx). Compound identification, multivariate/univariate data analysis and pathway analysis were performed subsequently. The diversity of the bacterial communities in the gastrointestinal content was measured using 16S rRNA gene sequencing. Then, the integration analysis of gut microbiota and metabolome was performed. Results: After 2/3 PHx, the residual liver proliferated quickly in the first 3 days and had about 90% of its initial weight by the seventh day. The results of PLS-DA showed that a significant metabolic shift occurred at 6 h and 36 h after 2/3 PHx that was reversed at the late phase of liver regeneration. The α and ß-diversity of the gut microbiota significantly changed at the early stage of liver regeneration. Specifically, Escherichia Shigella, Lactobacillus, Akkermansia, and Muribaculaceae were the bacteria that changed the most considerably during liver regeneration. Further pathway analysis found the most influenced co-metabolized pathways between the host and gut bacteria including glycolysis, the TCA cycle, arginine metabolism, glutathione metabolism, tryptophan metabolism, and purine and pyrimidine metabolism. Specifically, steroid hormone biosynthesis is the most significant pathway of the host during liver regeneration. Discussion: These findings revealed that during liver regeneration, there was a broad modification of gut microbiota and systemic metabolism and they were strongly correlated. Targeting specific gut bacterial strains, especially increasing the abundance of Akkermansia and decreasing the abundance of Enterobacteriaceae, may be a promising beneficial strategy to modulate systemic metabolism such as amino acid and nucleotide metabolism and promote liver regeneration.
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The anti-nerve growth factor antibody class of drugs interrupts signaling by blocking NGF binding to TrkA receptors for the treatment of pain; however, this target class of drugs has been associated with serious adverse effects in the joints during clinical trials. DS002 is a novel anti-nerve growth factor antibody drug independently developed by Guangdong Dashi Pharmaceuticals. The main purpose of this study is to explore the correlation between DS002 and pain as well as cartilage and bone metabolism with the help of metabolomics technology and the principle of enzyme-linked reaction, and to examine whether DS002 will produce serious adverse effects in joints caused by its same target class of drugs, in order to provide more scientific basis for the safety and efficacy of DS002. Our results showed that DS002 mainly affected the metabolism of aromatic amino acids and other metabolites, of which six metabolites, l -phenylalanine, 5-hydroxytryptophan, 5-hydroxytryptamine hydrochloride, 3-indolepropionic acid, kynuric acid, and kynurenine, were significantly altered, which may be related to the effectiveness of DS002 in treating pain. In addition, there were no significant changes in biological indicators related to cartilage and bone metabolism in vivo, suggesting that DS002 would not have a significant effect on cartilage and bone metabolism, so we hypothesize that DS002 may not produce the serious adverse effects in joints caused by its fellow target analogs. Therefore, the Anti-NGF analgesic drug DS002 has the potential to become a promising drug in the field of analgesia, providing pain patients with an efficient treatment option without adverse effects.
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Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require to multiply, once thought to be a characteristic of tumor cells known as the "Warburg effect". In fact, throughout the process of carcinogenesis, immune cells and stromal cells, two major cellular constituents of the tumor microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. In this review, we provide a full-scale review of the glycolytic remodeling of several types of TME cells and show how these TME cells behave in the acidic milieu created by glucose shortage and lactate accumulation as a result of increased tumor glycolysis. Notably, we provide an overview of putative targets and inhibitors of glycolysis along with the viability of using glycolysis inhibitors in combination with immunotherapy and chemotherapy. Understanding the glycolytic situations in diverse cells within the tumor immunological milieu will aid in the creation of subsequent treatment plans.
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The accurate and rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) holds significant clinical importance. This work presents a new method for detecting methicillin-resistant Staphylococcus aureus (S. aureus) in clinical samples. The method uses an aptamer-based colorimetric assay that combines a recognizing probe to identify the target and split DNAzyme to amplify the signal, resulting in a highly sensitive and direct analysis of methicillin-resistance. The identification of the PBP2a protein on the membrane of S. aureus in clinical samples leads to the allosterism of the recognizing probe, and thus provides a template for the proximity ligation of split DNAzyme. The proximity ligation of split DNAzyme forms an intact DNAzyme to identify the loop section in the L probe and generates a nicking site to release the loop sequence ("3" and "4" fragments). The "3" and "4" fragments forms an intact sequence to induce the catalytic hairpin assembly, exposing the G-rich section. The released the G-rich sequence of LR probe induces the formation of G-quadruplex-hemin DNAzyme as a colorimetric signal readout. The absorption intensity demonstrated a strong linear association with the logarithm of the S. aureus concentration across a wide range of 5 orders of magnitude dynamic range under the optimized experimental parameters. The limit of detection was calculated to be 23 CFU/ml and the method showed high selectivity for MRSA.
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Aptámeros de Nucleótidos , Colorimetría , ADN Catalítico , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , ADN Catalítico/metabolismo , Colorimetría/métodos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/diagnóstico , Humanos , Técnicas Biosensibles/métodos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Sensibilidad y Especificidad , Resistencia a la Meticilina , Proteínas de Unión a las Penicilinas/metabolismo , Proteínas de Unión a las Penicilinas/genéticaRESUMEN
Background: The efficacy and optimal dose of the new acid-suppressant vonoprazan (VPZ) for quadruple therapy remain uncertain. This study aimed to compare the efficacy and safety of 20 mg VPZ daily (VOD) and 20 mg VPZ twice daily (VTD) with a proton pump inhibitor (PPI) twice daily in quadruple therapy. Methods: We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori. Eradication rates and adverse events were compared between the VOD and VTD groups, and between the VOD and PPI groups. Multivariate analysis was conducted to identify the predictors of eradication failure. Results: Eradication was successful in 875 (91.7%) of the 954 patients. The total, initial, and rescue eradication rates in the VOD group were 92.1%, 93.3%, and 77.8%, respectively. In both the crude and multivariate analyses, the VOD group showed eradication rates comparable to those of the VTD and PPI groups (all P > 0.05). Age > 60 years (odds ratio [OR] = 2.165, P = 0.012) and use of rescue therapy (OR = 3.496, P < 0.001) were independent risk factors for eradication failure, whereas VPZ at a low dosing frequency of 20 mg daily was not. A total of 787 patients (82.5%) were followed up (mean follow-up time, 6.7 ± 2.0 months). Compared with the VOD group, the VTD group was more likely to experience adverse events (OR = 2.073, P = 0.035). Conclusion: VPZ at a low dose of 20 mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.
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Hepatocellular carcinoma (HCC) is one of the deadliest cancers of human, the tumor-related death of which ranks third among the common malignances. N6-methyladenosine (m6A) methylation, the most abundant internal modification of RNA in mammals, participates in the metabolism of mRNA and interrelates with ncRNAs. In this paper, we overviewed the complex function of m6A regulators in HCC, including regulating the tumorigenesis, progression, prognosis, stemness, metabolic reprogramming, autophagy, ferroptosis, drug resistance and tumor immune microenvironment (TIME). Furthermore, we elucidated the interplay between m6A modification and non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Finally, we summarized the potential of m6A regulators as diagnostic biomarkers. What's more, we reviewed the inhibitors targeting m6A enzymes as promising therapeutic targets of HCC. We aimed to help understand the function of m6A methylation in HCC systematically and comprehensively so that more effective strategies for HCC treatment will be developed.
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Adenosina/análogos & derivados , Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Animales , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Mamíferos , Microambiente TumoralRESUMEN
GOALS: A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap. BACKGROUND: It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups. STUDY: This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale. RESULTS: (1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) ( P <0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] ( P <0.01), and increased postdrinking symptoms, anxiety ( P <0.01), and depression ( P <0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV ( P <0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS ( P <0.05 for all) and PDS ( P <0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P =0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups. CONCLUSIONS: The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.
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Dispepsia , Gastritis , Humanos , Dolor Abdominal/etiología , Dolor Abdominal/diagnóstico , Gastritis/complicaciones , Periodo Posprandial/fisiologíaRESUMEN
The migrasome is a new organelle discovered by Professor Yu Li in 2015. When cells migrate, the membranous organelles that appear at the end of the retraction fibres are migrasomes. With the migration of cells, the retraction fibres which connect migrasomes and cells finally break. The migrasomes detach from the cell and are released into the extracellular space or directly absorbed by the recipient cell. The cytoplasmic contents are first transported to the migrasome and then released from the cell through the migrasome. This release mechanism, which depends on cell migration, is named 'migracytosis'. The main components of the migrasome are extracellular vesicles after they leave the cell, which are easy to remind people of the current hot topic of exosomes. Exosomes are extracellular vesicles wrapped by the lipid bimolecular layer. With extensive research, exosomes have solved many disease problems. This review summarizes the differences between migrasomes and exosomes in size, composition, property and function, extraction method and regulation mechanism for generation and release. At the same time, it also prospects for the current hotspot of migrasomes, hoping to provide literature support for further research on the generation and release mechanism of migrasomes and their clinical application in the future.
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Exosomas , Vesículas Extracelulares , Humanos , Exosomas/metabolismo , Orgánulos/metabolismo , Movimiento Celular/fisiología , Transporte BiológicoRESUMEN
BACKGROUND: Anti-folate drug pemetrexed is a vital chemotherapy medication for non-small cell lung cancer (NSCLC). Its response varies widely and often develops resistance to the treatment. Therefore, it is urgent to identify biomarkers and establish models for drug efficacy evaluation and prediction for rational drug use. METHODS: A total of 360 subjects were screened and 323 subjects were recruited. Using metabolomics in combination with machine learning methods, we are trying to select potential biomarkers to diagnose NSCLC and evaluate the efficacy of pemetrexed in treating NSCLC. Furtherly, we measured the concentration of eight metabolites in the tryptophan metabolism pathway in the validation set containing 201 subjects using a targeted metabolomics method with UPLC-MS/MS. RESULTS: In the discovery set containing 122 subjects, the metabolic profile of healthy controls (H), newly diagnosed NSCLC patients (ND), patients who responded well to pemetrexed treatment (S) and pemetrexed-resistant patients (R) differed significantly on the PLS-DA scores plot. Pathway analysis showed that glycine, serine and threonine metabolism occurred in every two group comparisons. TCA cycle, pyruvate metabolism and glycerolipid metabolism are the most significantly changed pathways between ND and H group, pyruvate metabolism was the most altered pathway between S and ND group, and tryptophan metabolism was the most changed pathway between S and R group. We found Random forest method had the maximum area under the curve (AUC) and can be easily interpreted. The AUC is 0.981 for diagnosing patients with NSCLC and 0.954 for evaluating pemetrexed efficiency. CONCLUSION: We compared eight mathematical models to evaluate pemetrexed efficiency for treating NSCLC. The Random forest model established with metabolic markers tryptophan, kynurenine and xanthurenic acidcan accurately diagnose NSCLC and evaluate the response of pemetrexed.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Pemetrexed/uso terapéutico , Triptófano/uso terapéutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Cromatografía Liquida , Espectrometría de Masas en Tándem , Biomarcadores , Piruvatos/uso terapéuticoRESUMEN
Exosomes carry and transmit signaling molecules used for intercellular communication. The generation and secretion of exosomes is a multistep interlocking process that allows simultaneous control of multiple regulatory sites. Protein molecules, mainly RAB GTPases, cytoskeletal proteins and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE), are specifically regulated in response to pathological conditions such as altered cellular microenvironment, stimulation by pathogenic factors, or gene mutation. This interferes with the smooth functioning of endocytosis, translocation, degradation, docking and fusion processes, leading to changes in the secretion of exosomes. Large numbers of secreted exosomes are disseminated by the flow of body fluids and absorbed by the recipient cells. By transmitting characteristic functional proteins and genetic information produced under disease conditions, exosomes can change the physiological state of the recipient cells and their microenvironment. The microenvironment, in turn, affects the occurrence and development of disease. Therefore, this review will discuss the mechanism by which exosome secretion is regulated in cells following the formation of mature secretory multivesicular bodies (MVBs). The overall aim is to find ways to eliminate disease-derived exosomes at their source, thereby providing an important new basis for the clinical treatment of disease.
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Introduction: Polysaccharides from Grifola frondosa (Dicks.) Gray (HSH) and Inonotus obliquus (Fr.) Pilat (BHR) showed noticeable effects on dextran sulfate sodium (DSS)-induced colitis, but their systemic modulation effects have not been fully revealed. This study aimed to investigate the regulation of the gut microbiota and systemic metabolism by HSH and BHR in DSS-induced colitis. Methods: C57BL/6J mice were given DSS (2.5%) in water and were treated with HSH and BHR (200 mg/kg/day) by gavage. Body weight and colon length were recorded, and H&E and AB-PAS staining of the colon were conducted to evaluate the model and the protective effect of the polysaccharides. Additionally, an LC-QTOF/MS-based untargeted metabolomic platform was used to identify the metabolites in the serum, colon tissue, gut contents, and faeces and investigate differential metabolites and metabolic pathways. 16S rDNA gene sequencing was used to measure the composition of bacterial communities. Results: The results showed that the mouse colitis model was established successfully, as evidenced by an increased disease activity index score [2.83 ± 0.62 vs. 0.06 ± 0.14 (p < 0.001)] and shortened colon length [5.43 ± 0.64 cm vs. 7.04 ± 0.29 cm (p < 0.001)], and HSH and BHR ameliorated DSS-induced colitis by improving the disease activity index (2.17 ± 0.28 and 1.83 ± 0.29, respectively) and restoring the colon length (6.12 ± 0.30 cm and 6.62 ± 0.35 cm, respectively). HSH and BHR significantly modulated metabolites involved in aromatic amino acid metabolism, the citrate cycle, purine metabolism, pyrimidine metabolism, etc. HSH and BHR increased the Chao1 index by 64.25% and 60.25%, respectively, and they increased the Shannon index by 13.02% and 10.23%, respectively. They both reversed the increase in the abundances of g_Odoribacter, g_Clostridium, g_AF12, g_Parabacteroides and g_Turicibacter and reversed the decrease in the abundance of g_unclassified_Bacteria induced by DSS. Specifically, HSH reversed the reductions in g_unclassified_Lactobacillales and g_Ruminococcus, and BHR reversed the decreases in g_unidentified_Coriobacteriaceae and g_unclassified_Firmicutes. Discussion: These results suggested that HSH and BHR may ameliorate DSS-induced colitis by global modulation of systemic metabolism and the gut microbiota. Targeting the gut microbiota may be a potentially effective strategy to modulate systemic metabolism and treat colitis.
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Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.
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ABSTRACT: Isoprenylation is an important post-transcriptional modification of small GTPases required for their activation and function. Isoprenoids, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate, are indispensable for isoprenylation by serving as donors of a prenyl moiety to small G proteins. In the human body, isoprenoids are mainly generated by the mevalonate pathway (also known as the cholesterol-synthesis pathway). The hydroxymethylglutaryl coenzyme A reductase catalyzes the first rate-limiting steps of the mevalonate pathway, and its inhibitor (statins) are widely used as lipid-lowering agents. In addition, the FPP synthase is also of critical importance for the regulation of the isoprenoids production, for which the inhibitor is mainly used in the treatment of osteoporosis. Synthetic FPP can be further used to generate geranylgeranyl pyrophosphate and cholesterol. Recent studies suggest a role for isoprenoids in the genesis and development of cardiovascular disorders, such as pathological cardiac hypertrophy, fibrosis, endothelial dysfunction, and fibrotic responses of smooth-muscle cells. Furthermore, statins and FPP synthase inhibitors have also been applied for the management of heart failure and other cardiovascular diseases rather than their clinical use for hyperlipidemia or bone diseases. In this review, we focus on the function of several critical enzymes, including hydroxymethylglutaryl coenzyme A reductase, FPP synthase, farnesyltransferase, and geranylgeranyltransferase in the mevalonate pathway which are involved in regulating the generation of isoprenoids and isoprenylation of small GTPases, and their pathophysiological role in the cardiovascular system. Moreover, we summarize recent research into applications of statins and the FPP synthase inhibitors to treat cardiovascular diseases, rather than for their traditional indications respectively.
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Sistema Cardiovascular/enzimología , Farnesiltransferasa/metabolismo , Geraniltranstransferasa/metabolismo , Hidroximetilglutaril-CoA Reductasas/metabolismo , Ácido Mevalónico/metabolismo , Proteínas de Unión al GTP Monoméricas/metabolismo , Colesterol/metabolismo , Humanos , Fosfatos de Poliisoprenilo/metabolismo , Prenilación de Proteína , Sesquiterpenos/metabolismoRESUMEN
OBJECTIVE: To systematically evaluate the efficacy and safety differences between acupuncture-moxibustion at acute stage and non-acute stage for peripheral facial paralysis. METHODS: The clinical trials regarding acupuncture- moxibustion for peripheral facial paralysis published before May 31st 2019 were searched in databases of CNKI, WF, VIP, SinoMed, PubMed, Cochrane Library and Google Scholar. The information of included studies was extracted and the quality was assessed by two independent researchers. The Meta-analysis was performed by using RevMan 5.3 software. RESULTS: A total of 11 trials were included, involving 1741 patients. The Meta-analysis results showed that: (1) the curative rate of acupuncture-moxibustion at acute stage was higher than that at non-acute stage (OR=2.45, 95%CI: 1.91-3.14, Z=7.06, P<0.01); (2) the average curative time of acupuncture-moxibustion at acute stage were shorter than that of non-acute stage (WMD=5.26, 95%CI: 3.44, 7.08, Z=5.67, P<0.01); (3) the incidence rate of sequelae in 6-month follow up of acupuncture-moxibustion at acute stage were lower than that of non-acute stage (OR=2.71, 95%CI: 1.26, 5.84, Z=2.56, P<0.05); (4) one study reported that there were no adverse reactions during treatment in both treatment group and control group. CONCLUSION: Based on current evidence, the efficacy of acupuncture-moxibustion at acute stage is superior to non-acute stage, which could promote the recovery of the disease and shorten the course of treatment, and reduce the occurrence of sequelae. More high-quality, large-sample randomized controlled trials are needed for further verification.
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Terapia por Acupuntura , Parálisis Facial/terapia , Moxibustión , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: Pancreatic cancer is one of the most common malignant cancers worldwide. Currently, the pathogenesis of pancreatic cancer remains unclear; thus, it is necessary to explore its precise molecular mechanisms. METHODS: To identify candidate genes involved in the tumorigenesis and proliferation of pancreatic cancer, the microarray datasets GSE32676, GSE15471 and GSE71989 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between Pancreatic ductal adenocarcinoma (PDAC) and nonmalignant samples were screened by GEO2R. The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool was used to obtain a synthetic set of functional annotation information for the DEGs. A PPI network of the DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and a combination of more than 0.4 was considered statistically significant for the PPI. Subsequently, we visualized the PPI network using Cytoscape. Functional module analysis was then performed using Molecular Complex Detection (MCODE). Genes with a degree ≥10 were chosen as hub genes, and pathways of the hub genes were visualized using ClueGO and CluePedia. Additionally, GenCLiP 2.0 was used to explore interactions of hub genes. The Literature Mining Gene Networks module was applied to explore the cocitation of hub genes. The Cytoscape plugin iRegulon was employed to analyze transcription factors regulating the hub genes. Furthermore, the expression levels of the 13 hub genes in pancreatic cancer tissues and normal samples were validated using the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Moreover, overall survival and disease-free survival analyses according to the expression of hub genes were performed using Kaplan-Meier curve analysis in the cBioPortal online platform. The relationship between expression level and tumor grade was analyzed using the online database Oncomine. Lastly, the eight snap-frozen tumorous and adjacent noncancerous adjacent tissues of pancreatic cancer patients used to detect the CDK1 and CEP55 protein levels by western blot. CONCLUSIONS: Altogether, the DEGs and hub genes identified in this work can help uncover the molecular mechanisms underlying the tumorigenesis of pancreatic cancer and provide potential targets for the diagnosis and treatment of this disease.
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BACKGROUND: Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease. Reports of malignant change of heterotopic pancreas are scarce. CASE SUMMARY: A 44-year-old Chinese female underwent a gastroscopy to assess abdominal distension that had persisted for 2 months. A protruding lesion in the gastric antrum was revealed but no malignant tissue was found in the biopsy specimen. The patient's symptom persisted and progressed to repeated vomiting. Endoscopy after 4 months revealed obstruction of the gastric outlet caused by the protruding lesion. A distal gastrectomy was performed. Histopathological examination of the surgical specimen showed the malignant transformation of aberrant pancreas in the stomach. Chemotherapy consisting of folinic acid, fluorouracil, and oxaliplatin was administered for three cycles, and was changed to gemcitabine monotherapy because of adverse effects and increased serum tumor marker levels. The patient remained asymptomatic during a 12-month follow-up. CONCLUSION: Pancreatic heterotopy should be considered as source of a potentially malignant lesion, and early treatment or close monitoring for aberrant pancreas is recommended.
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BACKGROUND: Food safety has become a major issue, with serious environmental pollution resulting from losses of nitrogen (N) fertilizers. N is a key element for plant growth and is often one of the most important yield-limiting nutrients in paddy soil. Urea-N immobilization is an important process for restoring the levels of soil nutrient depleted by rice production and sustaining productivity. The benefits of biochar application include improved soil fertility, altered N dynamics, and reduced nutrient leaching. However, due to high variability in the quality of biochar, the responses of N loss and rice productivity to biochar amendments, especially those prepared at different pyrolysis temperatures, are still unclear. The main objectives of the present study were to examine the effects of biochar prepared at different pyrolysis temperatures on fertilizer N immobilization in paddy soil and explore the underlying mechanisms. METHODS: Two biochar samples were prepared by pyrolysis of maize straw at 400 °C (B400) and 700 °C (B700), respectively. The biochar was applied to paddy soil at three rates (0, 0.7, and 2.1%, w/w), with or without N fertilization (0, 168, and 210 kg N ha-1). Pot experiments were performed to determine nitrous oxide (N2O) emissions and 15N recovery from paddy soil using a 15N tracer across the rice growing season. RESULTS: Compared with the non-biochar control, biochar significantly decreased soil bulk density while increasing soil porosity, irrespective of pyrolysis temperature and N fertilizer level. Under B400 and B700, a high biochar rate decreased N loss rate to 66.42 and 68.90%, whereas a high N level increased it to 77.21 and 76.99%, respectively. Biochar also markedly decreased N2O emissions to 1.06 (B400) and 0.75 kg ha-1 (B700); low-N treatment caused a decrease in N2O emissions under B400, but this decrease was not observed under B700. An application rate of biochar of 2.1% plus 210 kg ha-1 N fertilizer substantially decreased the N fertilizer-induced N2O emission factor under B400, whereas under B700 no significant difference was observed. Biochar combined with N fertilizer treatment decreased rice biomass and grain yield by an average of 51.55 and 23.90 g pot-1, respectively, but the yield reduction under B700 was lower than under B400. CONCLUSION: Irrespective of pyrolysis temperature, biochar had a positive effect on residual soil 15N content, while it negatively affected the 15N recovery of rice, N2O emissions from soil, rice biomass, and grain yield in the first year. Generally, a high application rate of biochar prepared at high or low pyrolysis temperature reduced the N fertilizer-induced N2O emission factor considerably. These biochar effects were dependent on N fertilizer level, biochar application rate, and their interactions.
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Psychological stress has been recognized as a well-documented risk factor associated with ß2-adrenergic receptor (ß2-AR) in the development of pancreatic cancer. Aldo-keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of ß2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and ß2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing ß2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of ß2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased ß2-AR levels and increased that of p-ERK1/2. Taken together, ß2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the ß2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.
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Aldehído Reductasa/genética , Neoplasias Pancreáticas/genética , Receptores Adrenérgicos beta 2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Aldehído Reductasa/metabolismo , Aldo-Ceto Reductasas , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Masculino , Persona de Mediana Edad , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Páncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Adrenérgicos beta 2/genética , Transducción de Señal/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Two-dimensional (2D) SnS2 materials represent a class of high-capacity candidates as anodes of Li-ion batteries (LIBs); however, they are limited by inferior rate and cycling performance. Herein, we demonstrate unique triaxial nanocables of conducting polypyrrole@SnS2@carbon nanofiber (PPy@SnS2@CNF) prepared via a facile combination of hydrothermal method and vapor-phase polymerization. The PPy@SnS2@CNF manifests a strong synergistic effect from its hierarchical nanoarchitecture, which provides enlarged electrode/electrolyte contact interfaces, highly electrical conductive pathways, sufficient electrolyte ingress/transport channels, and an intimate mechanical/electrochemical safeguard for fast electrode kinetics and good structural stability. When evaluated as binder-free anodes of LIBs, the ternary nanocomposite delivers an ultrahigh reversible capacity of 1165 mAh g-1 after 100 cycles and outstanding rate/cycling performance (880 mAh g-1 at 2000 mA g-1), which are among the best results of the previously reported SnS2 electrodes. This work may pave a rational avenue of developing 2D materials with hierarchical structures for highly efficient energy-storage systems.
RESUMEN
A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS2@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS2 nanosheets, thus hierarchically constructing coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS2 nanostructures. As a result, the MoS2@carbon composites-when serving as anodes for Li-ion batteries-exhibit a high reversible specific capacity of 820 mAh·g-1, high-rate capability (457 mAh·g-1 at 2 A·g-1), and excellent cycling stability. The use of bio-mass-derived carbon makes the MoS2@carbon composites low-cost and promising anode materials for high-performance Li-ion batteries.