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BACKGROUND: Information transmission between primary tumor cells and immunocytes or stromal cells in distal organs is a critical factor in the formation of pre-metastatic niche (PMN). Understanding this mechanism is essential for developing effective therapeutic strategy against tumor metastasis. Our study aims to prove the hypothesis that circ-0034880-enriched tumor-derived extracellular vesicles (TEVs) mediate the formation of PMN and colorectal cancer liver metastasis (CRLM), and targeting circ-0034880-enriched TEVs might be an effective therapeutic strategy against PMN formation and CRLM. METHODS: We utilized qPCR and FISH to measure circRNAs expression levels in human CRC plasma, primary CRC tissues, and liver metastatic tissues. Additionally, we employed immunofluorescence, RNA sequencing, and in vivo experiments to assess the effect mechanism of circ-0034880-enriched TEVs on PMN formation and CRC metastasis. DARTS, CETSA and computational docking modeling were applied to explore the pharmacological effects of Ginsenoside Rb1 in impeding PMN formation. RESULTS: We found that circ-0034880 was highly enriched in plasma extracellular vesicles (EVs) derived from CRC patients and closely associated with CRLM. Functionally, circ-0034880-enriched TEVs entered the liver tissues and were absorbed by macrophages in the liver through bloodstream. Mechanically, TEVs-released circ-0034880 enhanced the activation of SPP1highCD206+ pro-tumor macrophages, reshaping the metastasis-supportive host stromal microenvironment and promoting overt metastasis. Importantly, our mechanistic findings led us to discover that the natural product Ginsenoside Rb1 impeded the activation of SPP1highCD206+ pro-tumor macrophages by reducing circ-0034880 biogenesis, thereby suppressing PMN formation and inhibiting CRLM. CONCLUSIONS: Circ-0034880-enriched TEVs facilitate strong interaction between primary tumor cells and SPP1highCD206+ pro-tumor macrophages, promoting PMN formation and CRLM. These findings suggest the potential of using Ginsenoside Rb1 as an alternative therapeutic agent to reshape PMN formation and prevent CRLM.
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Neoplasias Colorretais , Vesículas Extracelulares , Neoplasias Hepáticas , Osteopontina , RNA Circular , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Vesículas Extracelulares/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Animais , RNA Circular/genética , Osteopontina/metabolismo , Osteopontina/genética , Linhagem Celular Tumoral , Microambiente Tumoral , Masculino , Feminino , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.
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Regulação da Expressão Gênica de Plantas , Inativação Gênica , Oryza , Proteínas de Plantas , Transgenes , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Mutação/genética , Domínios Proteicos , Haplótipos/genética , Metilação de DNA/genética , Ligação Proteica , Plantas Geneticamente Modificadas , AlelosRESUMO
The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.
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Antibacterianos , Carbolinas , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Carbolinas/farmacologia , Carbolinas/química , Carbolinas/síntese química , Humanos , Relação Estrutura-Atividade , Animais , Camundongos , Bactérias Gram-Positivas/efeitos dos fármacos , Estrutura Molecular , Bactérias Gram-Negativas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacosRESUMO
Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.
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MicroRNAs , Músculo Liso Vascular , Becaplermina/farmacologia , Proliferação de Células , Miócitos de Músculo Liso , Fenótipo , MicroRNAs/genética , Movimento Celular , Células CultivadasRESUMO
BACKGROUND: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. METHODS: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. RESULTS: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1ß, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. CONCLUSIONS: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.
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Golpe de Calor , Hipotálamo , Proteômica , Ratos Sprague-Dawley , Animais , Hipotálamo/metabolismo , Golpe de Calor/metabolismo , Ratos , Masculino , Esforço Físico/fisiologia , Modelos Animais de DoençasRESUMO
Four new clerodane diterpenoids, namely tinocapills A-D (1-4), and one known analogue (5) were isolated from the roots of Tinospora capillipes in the present study. The structures of these new compounds, including their absolute configurations, were determined through a combination of detailed spectroscopic analysis and theoretical statistical approaches, including electronic circular dichroism (ECD) analyses and quantum mechanical (QM)-NMR methods. Additionally, the stereostructure of 5 was confirmed via X-ray diffraction analysis. Furthermore, all these isolates were evaluated for their antibacterial and anti-inflammatory activities. Compounds 1, 2 and 5 demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 4-64â µg/mL, and compounds 3 and 4 exhibited potential anti-inflammatory effects by suppressing LPS-induced TNF-α and NO releases in RAW264.7 cells.
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Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.
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Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Xantonas , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Xantonas/farmacologia , Camundongos , Masculino , Colite/tratamento farmacológico , Colite/induzido quimicamente , Doenças Metabólicas/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Anti-Inflamatórios/farmacologia , Modelos Animais de DoençasRESUMO
PURPOSE: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC. METHODS: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0. RESULTS: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05). CONCLUSIONS: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.
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Transtornos da Coagulação Sanguínea , Coagulação Intravascular Disseminada , Golpe de Calor , Trombose , Humanos , Adolescente , Estudos Retrospectivos , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/etiologia , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos da Coagulação Sanguínea/etiologia , Golpe de Calor/complicaçõesRESUMO
Peroxisome proliferator-activated receptor γ (PPARγ) plays a pivotal role in regulating lipid metabolism and hepatic PPARγ transactivation contributes to fatty liver development. Fatty acids (FAs) are well-known endogenous ligands for PPARγ. Palmitate, a 16-C saturated FA (SFA) and the most abundant SFA in human circulation, is a strong inducer of hepatic lipotoxicity, a central pathogenic factor for various fatty liver diseases. In this study, using both alpha mouse liver 12 (AML12) and primary mouse hepatocytes, we investigated the effects of palmitate on hepatic PPARγ transactivation and underlying mechanisms, as well as the role of PPARγ transactivation in palmitate-induced hepatic lipotoxicity, all of which remain ambiguous currently. Our data revealed that palmitate exposure was concomitant with both PPARγ transactivation and upregulation of nicotinamide N-methyltransferase (NNMT), a methyltransferase catalyzing the degradation of nicotinamide, the predominant precursor for cellular NAD+ biosynthesis. Importantly, we discovered that PPARγ transactivation by palmitate was blunted by NNMT inhibition, suggesting that NNMT upregulation plays a mechanistic role in PPARγ transactivation. Further investigations uncovered that palmitate exposure is associated with intracellular NAD+ decline and NAD+ replenishment with NAD+-enhancing agents, nicotinamide and nicotinamide riboside, obstructed palmitate-induced PPARγ transactivation, implying that cellular NAD+ decline resulted from NNMT upregulation represents a potential mechanism behind palmitate-elicited PPARγ transactivation. At last, our data showed that the PPARγ transactivation marginally ameliorated palmitate-induced intracellular triacylglycerol accumulation and cell death. Collectively, our data provided the first-line evidence supporting that NNMT upregulation plays a mechanistic role in palmitate-elicited PPARγ transactivation, potentially through reducing cellular NAD+ contents.NEW & NOTEWORTHY Hepatic PPARγ transactivation contributes to fatty liver development. Saturated fatty acids (SFAs) induce hepatic lipotoxicity. Here, we investigated whether and how palmitate, the most abundant SFA in the human blood, affects PPARγ transactivation in hepatocytes. We reported for the first time that upregulation of nicotinamide N-methyltransferase (NNMT), a methyltransferase catalyzing the degradation of nicotinamide, the predominant precursor for cellular NAD+ biosynthesis, plays a mechanistic role in regulating palmitate-elicited PPARγ transactivation through reducing intracellular NAD+ contents.
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Fígado Gorduroso , Palmitatos , Camundongos , Animais , Humanos , Palmitatos/toxicidade , Nicotinamida N-Metiltransferase/genética , Nicotinamida N-Metiltransferase/metabolismo , Regulação para Cima , NAD/metabolismo , Ativação Transcricional , PPAR gama/genética , PPAR gama/metabolismo , Hepatócitos/metabolismo , Niacinamida/metabolismo , Niacinamida/farmacologia , Ácidos Graxos/metabolismoRESUMO
Hepatic lipotoxicity plays a central role in the pathogenesis of nonalcoholic fatty liver disease; however, the underlying mechanisms remain elusive. Here, using both cultured hepatocytes (AML-12 cells and primary mouse hepatocytes) and the liver-specific gene knockout mice, we investigated the mechanisms underlying palmitate-elicited upregulation of CD36, a class B scavenger receptor mediating long-chain fatty acids uptake, and its role in palmitate-induced hepatolipotoxicity. We found that palmitate upregulates hepatic CD36 expression. Despite being a well-established target gene of PPARγ transactivation, our data demonstrated that the palmitate-induced CD36 upregulation in hepatocytes is in fact PPARγ-independent. We previously reported that the activation of ATF4, one of three canonical pathways activated upon endoplasmic reticulum (ER) stress induction, contributes to palmitate-triggered lipotoxicity in hepatocytes. In this study, our data revealed for the first time that ATF4 plays a critical role in mediating hepatic CD36 expression. Genetic inhibition of ATF4 attenuated CD36 upregulation induced by either palmitate or ER stress inducer tunicamycin in hepatocytes. In mice, tunicamycin upregulates liver CD36 expression, whereas hepatocyte-specific ATF4 knockout mice manifest lower hepatic CD36 expression when compared with control animals. Furthermore, we demonstrated that CD36 upregulation upon palmitate exposure represents a feedforward mechanism in that siRNA knockdown of CD36 in hepatocytes blunted ATF4 activation induced by both palmitate and tunicamycin. Finally, we confirmed that the ATF4-CD36 pathway activation contributes to palmitate-induced hepatolipotoxicity as genetic inhibition of either ATF4 or CD36 alleviated cell death and intracellular triacylglycerol accumulation. Collectively, our data demonstrate that CD36 upregulation by ATF4 activation contributes to palmitate-induced hepatic lipotoxicity.NEW & NOTEWORTHY We provided the initial evidence that ATF4 is a principal transcription factor mediating hepatic CD36 expression in that both palmitate- and ER stress-elicited CD36 upregulation was blunted by ATF4 gene knockdown in hepatocytes, and hepatocyte-specific ATF4 knockout mice manifested lower hepatic CD36 expression. We further confirmed that the ATF4-CD36 pathway activation contributes to palmitate-induced hepatolipotoxicity as genetic inhibition of either ATF4 or CD36 alleviated cell death and intracellular triacylglycerol accumulation in response to exogenous palmitate exposure.
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PPAR gama , Palmitatos , Animais , Camundongos , Palmitatos/toxicidade , Palmitatos/metabolismo , Regulação para Cima , Ativação Transcricional , PPAR gama/metabolismo , Tunicamicina/metabolismo , Hepatócitos/metabolismo , Estresse do Retículo Endoplasmático , Camundongos Knockout , Triglicerídeos/metabolismoRESUMO
PURPOSE: Study the impact of impaired sleep quality on symptom change and future exacerbation of chronic obstructive pulmonary disease (COPD) patients. METHODS: This was a prospective study. Patients with COPD were recruited into the study and followed up for one year. Pittsburgh sleep quality index (PSQI) was collected at baseline. Symptom change was assessed with Minimum clinically important difference (MCID) in COPD Assessment Test (CAT) at 6-month visit, which is an indicator to assess symptom improvement. Exacerbation was recorded during the one-year visit. PSQI score > 5 was defined as poor sleep quality, whereas PSQI score ≤ 5 was defined as good sleep quality. MCID was defined as attaining a CAT decrease ≥ 2. RESULTS: A total of 461 patients were enrolled for final analysis. Two hundred twenty-eight (49.4%) patients had poor sleep quality. Overall, 224 (48.6%) patients attained MCID at 6-month visit and the incidence of exacerbation during the one-year visit was 39.3%. Fewer patients with impaired sleep quality achieved MCID than patients with good sleep quality. Good sleepers were significantly more likely to attain MCID (OR: 3.112, p < 0.001) than poor sleepers. Fewer poor sleepers in GOLD A and D groups attained MCID with ICS/LABA, and fewer poor sleepers in the GOLD D group attained MCID with ICS/LABA/LAMA than good sleepers. Poor sleep quality was a greater risk factor of future exacerbation in Cox regression analysis. The ROC curves showed that PSQI score had a predictive capacity for future exacerbation. More patients with poor sleep quality experienced future exacerbation in GOLD B and D group with treatment of ICS/LABA/LAMA compared to good sleepers. CONCLUSIONS: COPD patients with impaired sleep quality were less likely to achieve symptom improvement and were at increased risk of future exacerbation compared to patients with good sleep quality. Besides, sleep disturbance may affect the symptom improvement and future exacerbation of patients with different inhaled medication or in different GOLD groups.
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Doença Pulmonar Obstrutiva Crônica , Qualidade do Sono , Humanos , Estudos Prospectivos , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fatores de Risco , Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas Muscarínicos , Administração por Inalação , CorticosteroidesRESUMO
Hypoxia-ischemia (HI) during crucial periods of brain formation can lead to changes in brain morphology, propagation of neuronal stimuli, and permanent neurodevelopmental impairment, which can have profound effects on cognitive function later in life. FAM3A, a subgroup of family with sequence similarity 3 (FAM3) gene family, is ubiquitously expressed in almost all cells. Overexpression of FAM3A has been evidenced to reduce hyperglycemia via the PI3K/Akt signaling pathway and protect mitochondrial function in neuronal HT22 cells. This study aims to evaluate the protective role of FAM3A in HI-induced brain impairment. Experimentally, maternal rats underwent uterine artery bilateral ligation to induce neonatal HI on day 14 of gestation. At 6 weeks of age, cognitive development assessments including NSS, wire grip, and water maze were carried out. The animals were then sacrificed to assess cerebral mitochondrial function as well as levels of FAM3A, TNF-α and IFN-γ. Results suggest that HI significantly reduced FAM3A expression in rat brain tissues, and that overexpression of FAM3A through lentiviral transduction effectively improved cognitive and motor functions in HI rats as reflected by improved NSS evaluation, cerebral water content, limb strength, as well as spatial learning and memory. At the molecular level, overexpression of FAM3A was able to promote ATP production, balance mitochondrial membrane potential, and reduce levels of pro-inflammatory cytokines TNF-α and IFN-γ. We conclude that FAM3A overexpression may have a protective effect on neuron morphology, cerebral mitochondrial as well as cognitive function. Created with Biorender.com.
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Hipóxia-Isquemia Encefálica , Proteínas Proto-Oncogênicas c-akt , Animais , Ratos , Animais Recém-Nascidos , Encéfalo/metabolismo , Isquemia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Anisotropic shape-tunable polymer particles have gained significant attention for their wide applications, and their performances are usually strongly correlated to their shapes. In contrast to convex particles, the synthesis of highly uniform concave polymer particles remains a great challenge. Here, we present a facile and effective route to synthesize biconcave polystyrene (PS) discs by swelling-induced phase separation of hydrophilically modified PS microspheres and report an unexpected finding that even a tiny amount of hydrophilic units that were incorporated into PS microspheres can significantly change the shape of phase interfaces, resulting in the transformation of disc shapes from convex to flat to concave. This is realized by several typical hydrophilic monomers, such as sodium styrene sulfonate (NaSS), acrylic acid (AA), or (2-(methacryloyloxy)ethyl)trimethylammonium chloride (METAC). The effect of the distribution of hydrophilic units in microspheres was investigated, and the mechanism of shape tuning has been discussed. The curvatures of the bottom surfaces of discs show a strong correlation to the content of hydrophilic units. In particular, we emphasize that the shape control method is general since it does not depend on specific hydrophilic units. This research paves the way for precisely structuring polymer particle shapes, which is important for polymer particles to be used for self-assembly, diffusion, rheology, transport, filler, and many other applications.
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A 1,1'-bi-2-naphthol (BINOL)-derived disulfonimide (DSI)-catalyzed enantioselective aza-Friedel-Crafts reaction between 1,3,5-trialkoxy benzenes and N-sulfonyl aldimines gives direct access to a series of chiral diarylmethylamines in good yields and good to excellent enantioselectivities (up to 97% ee). This reaction provides a useful protocol for the direct synthesis of diarylmethylamine derivatives.
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Galectins are a family of evolutionarily conserved lectins that contain carbohydrate recognition domains (CRDs) specifically recognizing ß-galactoside. Galectin-9 plays a crucial role in various biological processes during pathogenic infections. In a previous study, galectin-9 was identified as a candidate gene for resistance to Vibrio harveyi disease in yellow drum using a genome-wide association study (GWAS) analysis. In this study, a galectin-9 gene was identified from Nibea albiflora and named YdGal-9. The mRNA transcripts of YdGal-9 were distributed in all the detected tissues and the highest level was found in the kidney. The subcellular localization of YdGal-9-EGFP proteins was observed in both nucleus and cytoplasm in the kidney cells of N. albiflora. The expression of YdGal-9 in the brain increased significantly after infection with Vibrio harveyi. The red blood cells from rabbits, Larimichthys crocea, and N. albiflora were agglutinated by the purified recombinant YdGal-9 proteins. The results of the agglutination activity of deletion mutants of YdGal-9 proved that the conserved sugar binding motifs (H-NPR and WG-EE-) were critical for YdGal-9's agglutination activity. In addition, YdGal-9 killed some gram-negative bacteria by inducing cell wall destruction including Pseudomonas plecoglossicida, Aeromonas hydrophila, Escherichia coli, V. parahemolyticus, V. harveyi, and V. alginolyticus. Taken together, these results suggested that the YdGal-9 protein of N. albiflora played a vital role in fighting bacterial infections.
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Perciformes , Vibrio , Animais , Coelhos , Estudo de Associação Genômica Ampla , Vibrio/genética , Galectinas/química , Perciformes/genética , Filogenia , Proteínas de Peixes/químicaRESUMO
BACKGROUND AND AIMS: We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model. METHODS: An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas. RESULTS: SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats. CONCLUSIONS: Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.
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Gabexato , Pancreatite , Ratos , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Gabexato/efeitos adversos , Poloxâmero/farmacologia , Interleucina-6 , Fator de Necrose Tumoral alfa , Ratos Sprague-Dawley , Ácido Taurocólico , Doença Aguda , Pâncreas/patologiaRESUMO
BACKGROUND: Foetal anaemia and umbilical vein thrombosis are rare pregnancy complications that can increase the risk of perinatal adverse events, which, in severe cases, can lead to foetal death. During pregnancy, umbilical vein varix (UVV) commonly occurs in the intra-abdominal part of the umbilical vein and is associated with an increased risk of foetal anaemia and umbilical vein thrombosis. However, UVV occurring in the extra-abdominal part of the umbilical vein is rare, especially when accompanied by thrombosis. In this case report, we describe a rare case of an extensive extra-abdominal umbilical vein varix (EAUVV), which ultimately resulted in foetal death due to umbilical vein thrombosis. CASE PRESENTATION: In this report, we describe a rare case of an extensive EAUVV that was discovered at 25 weeks and 3 days of gestation. During the examination, there were no abnormalities in foetal haemodynamics. The estimated weight of the foetus was only 709 g. In addition to refusing to be hospitalized, the patient refused close monitoring of the foetus. As a result, we were limited to choosing an expectant therapy. The foetus died 2 weeks after diagnosis and was confirmed to have EAUVV with thrombosis after the induction of labour. CONCLUSION: In the case of EAUVV, lesions are extremely rare, and it is very easy for thrombosis to form, which may result in the death of the child. When determining the next step in the treatment of the condition, the degree of UVV, possible complications, gestational age, foetal haemodynamics, and other relevant factors are strongly connected to the clinical therapy decision, and these factors should be considered comprehensively when making a clinical decision. We recommend close monitoring with hospital admission (to facilities capable of handling extremely preterm foetuses) after variability in delivery for worsening haemodynamic status.
Assuntos
Doenças Fetais , Trombose , Varizes , Trombose Venosa , Gravidez , Feminino , Recém-Nascido , Criança , Humanos , Veias Umbilicais/diagnóstico por imagem , Ultrassonografia Pré-Natal , Varizes/complicações , Trombose Venosa/complicações , Morte Fetal/etiologiaRESUMO
In tunnel lining construction, the traditional manual wet spraying operation is labor-intensive and can be challenging to ensure consistent quality. To address this, this study proposes a LiDAR-based method for sensing the thickness of tunnel wet spray, which aims to improve efficiency and quality. The proposed method utilizes an adaptive point cloud standardization processing algorithm to address differing point cloud postures and missing data, and the segmented Lamé curve is employed to fit the tunnel design axis using the Gauss-Newton iteration method. This establishes a mathematical model of the tunnel section and enables the analysis and perception of the thickness of the tunnel to be wet sprayed through comparison with the actual inner contour line and the design line of the tunnel. Experimental results show that the proposed method is effective in sensing the thickness of tunnel wet spray, with important implications for promoting intelligent wet spraying operations, improving wet spraying quality, and reducing labor costs in tunnel lining construction.
Assuntos
Algoritmos , Trabalho de Parto , Gravidez , Feminino , Humanos , Computação em Nuvem , Inteligência , LasersRESUMO
BACKGROUND: The usage of natural polysaccharides is attractive to researchers around the world. At the same time, non-/low-toxic crosslinkers prepared by polysaccharides are expected to fabricate protein-based films in many fields. Herein, different dialdehyde polysaccharides (DPs) were successfully synthesized and applied to prepare gliadin-films under alkaline conditions. The functional properties and formation mechanisms of the films were fully investigated. RESULTS: The results showed that the mechanical properties, water-resistant properties, thermal stability, and antibacterial properties of the gliadin-films were improved by DPs and alkali treatment. Particularly dialdehyde dextrin (DAD) crosslinked gliadin-films showed the highest tensile strength, but no additional effect on their elongation, or advancement on the other functional properties. The film-forming mechanisms indicated that Schiff base bonds, hydrophobic interactions, electrostatic interactions, and hydrogen bonds were the main forces in the films, supporting their improvement in functional properties. CONCLUSION: DPs, especially DAD, can be a promising crosslinker in fabricating gliadin-films. These findings have shown great promise to seek an effective crosslinker for fabricating gliadin/protein-based packaging. © 2023 Society of Chemical Industry.
Assuntos
Gliadina , Água , Gliadina/química , Resistência à Tração , Água/química , Polissacarídeos , Embalagem de AlimentosRESUMO
Draconis Sanguis is a precious Chinese medicinal material for activating blood and resolving stasis, and its effective components are flavonoids. However, the structural diversity of flavonoids in Draconis Sanguis brings great challenges to the in-depth chara-cterization of its chemical composition profiles. To clarify the substance basis of Draconis Sanguis, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used in this study to acquire MS data of Draconis Sanguis. The molecular weight imprinting(MWI) and mass defect filtering(MDF) were developed for rapid screening of flavonoids in Draconis Sanguis. Full-scan MS and MS~2 were recorded within the mass range m/z 100-1 000 in positive ion mode. Accor-ding to previous literature, MWI was employed to hunt for reported flavonoids in Draconis Sanguis, and the mass tolerance range of [M+H]~+ was set as ±10×10~(-3). A five-point MDF screening frame was further constructed to narrow the screening range of flavonoids from Draconis Sanguis. Combined with diagnostic fragment ions(DFI) and neutral loss(NL) as well as mass fragmentation pathways, 70 compounds were preliminarily identified from the extract of Draconis Sanguis, including 5 flavan oxidized congeners, 12 flavans, 1 dihydrochalcones, 49 flavonoids dimers, 1 flavonoids trimer and 2 flavonoid derivatives. This study clarified the chemical composition of flavonoids in Draconis Sanguis. Moreover, it also showed that high-resolution MS combined with data post-processing methods such as MWI and MDF could achieve rapid characterization of the chemical composition in Chinese medicinal materials.