RESUMO
Tumor-derived extracellular vesicles are important mediators of cell-to-cell communication during tumorigenesis. Here, we demonstrated that hepatocellular carcinoma (HCC)-derived ectosomes remodel the tumor microenvironment to facilitate HCC progression in an ectosomal PKM2-dependent manner. HCC-derived ectosomal PKM2 induced not only metabolic reprogramming in monocytes but also STAT3 phosphorylation in the nucleus to upregulate differentiation-associated transcription factors, leading to monocyte-to-macrophage differentiation and tumor microenvironment remodeling. In HCC cells, sumoylation of PKM2 induced its plasma membrane targeting and subsequent ectosomal excretion via interactions with ARRDC1. The PKM2-ARRDC1 association in HCC was reinforced by macrophage-secreted cytokines/chemokines in a CCL1-CCR8 axis-dependent manner, further facilitating PKM2 excretion from HCC cells to form a feedforward regulatory loop for tumorigenesis. In the clinic, ectosomal PKM2 was clearly detected in the plasma of HCC patients. This study highlights a mechanism by which ectosomal PKM2 remodels the tumor microenvironment and reveals ectosomal PKM2 as a potential diagnostic marker for HCC.
Assuntos
Proteínas de Transporte/metabolismo , Micropartículas Derivadas de Células/metabolismo , Proteínas de Membrana/metabolismo , Hormônios Tireóideos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Micropartículas Derivadas de Células/genética , Micropartículas Derivadas de Células/patologia , Quimiocina CCL1/metabolismo , Progressão da Doença , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Monócitos/metabolismo , Prognóstico , Fator de Transcrição STAT3/metabolismo , Hormônios Tireóideos/genética , Microambiente Tumoral , Proteínas de Ligação a Hormônio da TireoideRESUMO
Water pollution, which continuously threatens human health and the sustainable development of society, has become a major concern. Photocatalytic degradation is an effective strategy to remove organic dyes from wastewater. For this strategy, it is crucial to select the appropriate catalyst. Using triphenylphosphine oxide (OPPh3) as the ligand, phosphomolybdic acid as the anion template, three new lanthanide complexes [Ln(OPPh3)4(H2O)3](PMo12O40)â4C2H5OH (1-3) (Ln = Sm, Gd, Tb) were synthesized. The raw materials for the reaction are cheap and readily available. The convenient synthesis method is environmentally friendly, with high yield (70%-80%). Complexes 1-3 are all seven-coordinated mononuclear structures centered on lanthanide ions, [PMo12O40]3- anions and solvent molecules are not coordinated with metal ions. These mononuclear structures eventually form complicated 3D supramolecular structures through hydrogen bonds, Mo-O π or C-H π weak interactions. Complexes 1-3 photocatalytic degradation of MB have high removal rates, as catalysts have enough stability to be reused, and can be used as excellent catalysts for the degradation of dye molecules in sewage. Among them, the removal rate of MB by photodegradation of complex 2 was highest (99.50%). In addition, the effects of different initial concentrations of MB solution and different types of organic dyes on the photocatalysis experiment were investigated. The photocatalytic reaction mechanism of complexes 1-3 was also studied. Due to the similar structures of complexes 1-3, they have almost the same THz absorption spectra with different absorption intensity, which may be attributed to the difference of the number of weak interactions. Therefore, terahertz spectroscopy can be used as a sensitive method to distinguish and determine small differences between lanthanide-organic complexes. This is the first time that this spectrum has been used to characterize lanthanide phosphine oxide complexes modified by [PMo12O40]3-.
Assuntos
Elementos da Série dos Lantanídeos , Fosfinas , Ânions , Humanos , Elementos da Série dos Lantanídeos/química , Óxidos , PolieletrólitosRESUMO
A series of rare earth complexes containing (α-PW12O40)3- and PO ligand are synthesized by water bath in 70 °C, [Ln(OPPh3)4(H2O)3](PW12O40)·4CH3CN (Ln = La, Pr, Nd, Sm, Gd, Tb, Ho 1-7) (OPPh3 = Triphenylphosphine oxide, {PW12} = phosphotungstic acid). The precise structures are confirmed by X-ray single crystal diffraction and the result shows all complexes are isostructural. Complexes 1-7 are fully characterized by PXRD, FT-IR, TGA, UV diffuse reflectance spectra and terahertz time-domain spectroscopy (THz-TDS). Complex 3 exhibits the highest photocatalytic degradation efficiency for methylene blue (MB) in this series of complexes. The experimental results showed that the photodegradation efficiency can remain constant at the level of 95% after five consecutive cycles. The photocatalytic reaction kinetics and mechanism of complexes were investigated. Additionally, complexes also exhibit photocatalytic hydrogen evolution activity. THz-TDS was used to characterize the complexes and its raw materials, the characteristic peaks of OPPh3 (broad peak at 1.20 THz) and phosphotungstic acid (sharp peaks at 0.23, 0.32 THz) were obtained.
Assuntos
Elementos da Série dos Lantanídeos , Óxidos , Fosfinas , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The design-build-test-learn (DBTL) cycle has been implemented in metabolic engineering processes for optimizing the production of valuable compounds, including food ingredients. However, the use of recombinant microorganisms for producing food ingredients is associated with different challenges, e.g., in the EU, a content of more than 0.9% of such ingredients requires to be labeled. Therefore, we propose to expand the DBTL cycle and use the "learn" module to guide the development of non-engineered strains for clean label production. Here, we demonstrate how this approach can be used to generate engineered and natural cell factories able to produce the valuable food flavor compound - butanedione (diacetyl). Through comprehensive rerouting of the metabolism of Lactococcus lactis MG1363 and re-installment of the capacity to metabolize lactose and dairy protein, we managed to achieve a high titer of diacetyl (6.7 g/L) in pure dairy waste. Based on learnings from the engineering efforts, we successfully achieved the production of diacetyl without using recombinant DNA technology. We accomplish the latter by process optimization and by relying on high-throughput screening using a microfluidic system. Our results demonstrate the great potential that lies in combining metabolic engineering and natural approaches for achieving efficient production of food ingredients.
Assuntos
Lactococcus lactis , Manteiga , Aromatizantes , Lactococcus lactis/genética , Lactose , OdorantesRESUMO
Identifying and overcoming the limitations preventing efficient high-yield production of chemicals remain important tasks in metabolic engineering. In an attempt to rewire Corynebacterium glutamicum to produce ethanol, we attained a low yield (63% of the theoretical) when using resting cells on glucose, and large amounts of succinate and acetate were formed. To prevent the by-product formation, we knocked out the malate dehydrogenase and replaced the native E3 subunit of the pyruvate dehydrogenase complex (PDHc) with that from Escherichia coli, which is active only under aerobic conditions. However, this tampering resulted in a 10-times-reduced glycolytic flux as well as a greatly increased NADH/NAD+ ratio. When we replaced glucose with fructose, we found that the glycolytic flux was greatly enhanced, which led us to speculate whether the source of reducing power could be the pentose phosphate pathway (PPP) that is bypassed when fructose is metabolized. Indeed, after shutting down the PPP by deleting the zwf gene, encoding glucose-6-phosphate dehydrogenase, the ethanol yield on glucose increased significantly, to 92% of the theoretical. Based on that, we managed to rechannel the metabolism of C. glutamicum into d-lactate with high yield, 98%, which is the highest that has been reported. It is further demonstrated that the PPP-inactivated platform strain can offer high-yield production of valuable chemicals using lactose contained in dairy waste as feedstock, which paves a promising way for potentially turning dairy waste into a valuable product.IMPORTANCE The widely used industrial workhorse C. glutamicum possesses a complex anaerobic metabolism under nongrowing conditions, and we demonstrate here that the PPP in resting C. glutamicum is a source of reducing power that can interfere with otherwise redox-balanced metabolic pathways and reduce yields of desired products. By harnessing this physiological insight, we employed the PPP-inactivated platform strains to produce ethanol, d-lactate, and alanine using the dairy waste whey permeate as the feedstock. The production yield was high, and our results show that inactivation of the PPP flux in resting cells is a promising strategy when the aim is to use nongrowing C. glutamicum cells for producing valuable compounds. Overall, we describe the benefits of disrupting the oxidative PPP in nongrowing C. glutamicum and provide a feasible approach toward waste valorization.
Assuntos
Biocombustíveis , Corynebacterium glutamicum/metabolismo , Etanol/metabolismo , Via de Pentose Fosfato , Transporte de Elétrons , ElétronsRESUMO
ß-galactosidases, commonly referred to as lactases, are used for producing lactose-free dairy products. Lactases are usually purified from microbial sources, which is a costly process. Here, we explored the potential that lies in using whole cells of a food-grade dairy lactic acid bacterium, Streptococcus thermophilus, as a substitute for purified lactase. We found that S. thermophilus cells, when treated with the antimicrobial peptide nisin, were able to hydrolyze lactose efficiently. The rate of hydrolysis increased with temperature; however, above 50 °C, stability was compromised. Different S. thermophilus strains were tested, and the best candidate was able to hydrolyze 80% of the lactose in a 50 g/L solution in 4 h at 50 °C, using only 0.1 g/L cells (dry weight basis). We demonstrated that it was possible to grow the cell catalyst on dairy waste, and furthermore, that a cell-free supernatant of a culture of a nisin-producing Lactococcus lactis strain could be used instead of purified nisin, which reduced cost of use significantly. Finally, we tested the cell catalysts in milk, where lactose also was efficiently hydrolyzed. The method presented is natural and low-cost, and allows for production of clean-label and lactose-free dairy products without using commercial enzymes from recombinant microorganisms. KEY POINTS: ⢠Nisin-permeabilized Streptococcus thermophilus cells can hydrolyze lactose efficiently. ⢠A low-cost and more sustainable alternative to purified lactase enzymes. ⢠Reduction of overall sugar content. ⢠Clean-label production of lactose-free dairy products.
Assuntos
Lactase/metabolismo , Lactobacillales/metabolismo , Animais , Permeabilidade da Membrana Celular/efeitos dos fármacos , Meios de Cultura , Hidrólise , Lactobacillales/crescimento & desenvolvimento , Lactococcus lactis/crescimento & desenvolvimento , Lactococcus lactis/metabolismo , Lactose/análise , Lactose/metabolismo , Leite/química , Leite/microbiologia , Nisina/metabolismo , Nisina/farmacologia , Streptococcus thermophilus/efeitos dos fármacos , Streptococcus thermophilus/crescimento & desenvolvimento , Streptococcus thermophilus/metabolismo , TemperaturaRESUMO
OBJECTIVE: To study the clinical application value of the penile erectile strength measurement (PESM) band in the differentiation of psychogenic from organic erectile dysfunction (ED). METHODS: Eighty ED patients unable to achieve or maintain adequate penile erection to complete sexual intercourse were included in the experimental group and another 40 healthy subjects with normal erectile function enrolled as controls. The ED cases were classified into mild, moderate and severe ED according to the IIEF-5 scores and divided into psychogenic and organic ED based on the results of the nocturnal penile tumescence (NPT) test. Then all the subjects underwent a three-night continuous monitoring with the PESM band and, according to the band fracture rate, the ED cases were also classified into psychogenic and organic ED. The rates of missed diagnosis, misdiagnosis and diagnostic coincidence of PESM were calculated with the results of NPT as the standard for differentiating psychogenic from organic ED. RESULTS: The results of NPT tests revealed 51 cases of psychogenic and 29 cases of organic ED in the experimental group. The band fracture rate in PESM was 95.0% in the mild, 80.9% in the moderate and 52.8% in the severe ED patients. Of the 51 cases of psychogenic ED detected by NPT test, 43 were diagnosed as psychogenic and the other 8 as organic ED with the PESM band, with a coincidence rate of 84.3%. Of the 29 cases of organic ED revealed by NPT test, 5 were diagnosed as psychogenic and the other 24 as organic ED by PESM, with a coincidence rate of 82.8%. Normal erectile function with three-level fracture of the band was observed in the PESM of the normal controls, which showed a coincidence rate of 100% with the results of NPT tests. Based on the standard of the NPT test, the rates of missed diagnosis, misdiagnosis and diagnostic coincidence of the PESM band in differentiating psychogenic from organic ED were 15.7%, 17.2%, and 83.8%, respectively, with a Kappa value of 0.656 (P <0.05). CONCLUSIONS: The penile erectile strength measurement band can be used as a screening tool for initial differentiation of psychogenic from organic ED.
Assuntos
Disfunção Erétil/classificação , Disfunção Erétil/fisiopatologia , Ereção Peniana/fisiologia , Estudos de Casos e Controles , Coito , Erros de Diagnóstico/estatística & dados numéricos , Disfunção Erétil/diagnóstico , Disfunção Erétil/psicologia , Humanos , MasculinoRESUMO
OBJECTIVE: To investigate the association of circumcision with the incidence of human papillomavirus (HPV) infection in men. METHODS: We collected the samples from the surface of the coronal sulcus, glans penis, penile shaft and scrotum of 351 males examined for HPV infection in our hospital from January 2016 to August 2017, of whom 118 had received circumcision while the other 233 had not. We compared the incidence rate of HPV infection between the circumcision and non-circumcision groups and analyzed the association of the age of circumcision with the incidence of HPV infection. RESULTS: HPV infection was found in 135 (38.46%) of the males, 29 (24.58%) in the circumcision group and 106 (45.49%) in the non-circumcision group, significantly lower in the former than in the latter (χ² = 14.48, P < 0.01). The incidence rate of HPV infection was also remarkably lower in the males circumcised at ≤17 years (13.16% ï¼»5/38ï¼½) than in those circumcised at >17 years of age (30.0% ï¼»24/80ï¼½) (χ² = 3.942, P = 0.047). CONCLUSIONS: Male circumcision helps reduce the incidence rate of HPV infection in men and earlier surgery may achieve even better effect.
Assuntos
Circuncisão Masculina/estatística & dados numéricos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Pênis/virologia , Escroto/virologia , Humanos , Incidência , Masculino , Infecções por Papillomavirus/diagnósticoRESUMO
With the development of endoscopic technique, Caldwell-Luc approach has more wide applications and becomes a common method of pterygopalatine fossa (PPF) surgery. Few data can be used in this approach to avoid injuring the vessels and nerves within this area. In this study, the authors used computed tomography to get the coordinates of inferior orbital fissure, foramen rotundum, sphenopalatine foramen, internal opening of pterygoid canal, the strangulation of PPF, and the greater palatine foramen with canine fossa as the origin. Parameters of 60 patients (120 observations) between 35 and 55 years who have no experience of trauma or surgery before were involved in this study. The data were analyzed by SPSS, statistical software with the comparison between sexes and sides. After calculating the relative distances and angles between these points and canine fossa, the authors get the proportions of the upper part of PPF, and the pterygopalatine canal to PPF, respectively. The authors finally got the safety surgical range. The results are meaningful to safety in surgery and complication avoidance, which can be great references in clinical applications.
Assuntos
Endoscopia/métodos , Fossa Pterigopalatina , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Humanos , Masculino , Seio Maxilar/anatomia & histologia , Seio Maxilar/diagnóstico por imagem , Pessoa de Meia-Idade , Órbita/anatomia & histologia , Órbita/diagnóstico por imagem , Fossa Pterigopalatina/anatomia & histologia , Fossa Pterigopalatina/diagnóstico por imagem , Fossa Pterigopalatina/cirurgia , Osso Esfenoide/anatomia & histologia , Osso Esfenoide/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the values of serum calculated free testosterone (cFT), testosterone secretion index (TSI), and free testosterone index (FTI) in the diagnosis of ED with androgen deficiency by observing their changes in the patient. METHODS: We conducted this study among 185 men complaining of ED and 35 20ï¼40 years old healthy males presenting at the clinic for premarital medical checkup. We asked them about their medical history, to fill in the International Index of Erectile Function (IIEF-5) Questionnaire, and to complete the nocturnal penile tumescence (NPT) test. According to the data obtained, 150 of the complainants were diagnosed as ED patients and 25 of the healthy examinees were included in the control group. We determined the levels of total serum testosterone (TT), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), serum albumin (ALB), cFT, bio-available testosterone (bio-T), TSI, and FTI in the two groups of subjects. Using cFT ≤0.3 nmol/L, TSI ≤2.8, and FTI ≤0.4 as the critical values and TT ≤11.5 nmol/L as the gold standard for androgen deficiency, we calculated cFT-, TSI-, and FTI-related rates of missed diagnosis, misdiagnosis, and diagnostic coincidence. RESULTS: With TT ≤11.5 nmol/L as the criterion, the cFT-, TSI-, and FTI-related rates of coincidence in the diagnosis of androgen deficiency in the ED patients were 90.8%, 85.8%, and 80.8%, those of missed diagnosis were 4.0%, 33.3%, and 44.0%, and those of misdiagnosis were 10.5%, 19.4%, and 12.6%, with the Kappa of values 0.755, 0.564, and 0.427, respectively (P <0.05). The levels of serum TT, cFT, Bio-T, TSI, and FTI were decreased with increased age of the 20ï¼40 years old ED patients, with statistically significant differences among different age groups except the serum TT level. However, no statistically significant differences were found in the levels of TT, cFT, Bio-T, TSI, and FTI among the patients with different IIEF-5 scores. CONCLUSIONS: The level of cFT has a higher value than those of TT, TSI, and TSI in the diagnosis of ED with androgen deficiency in 20ï¼40 years old men.
Assuntos
Disfunção Erétil/sangue , Disfunção Erétil/diagnóstico , Testosterona/sangue , Adulto , Androgênios/deficiência , Estudos de Casos e Controles , Humanos , Hormônio Luteinizante/sangue , Masculino , Albumina Sérica/análise , Globulina de Ligação a Hormônio Sexual/análise , Adulto JovemRESUMO
Oseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van't Hoff equation were - 77.49 kJ/mol, -176.54 J/(molâK), and - 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.
RESUMO
OBJECTIVE: To evaluate the effect of wrist-ankle acupuncture (WAA) in pain and functional recovery after total knee arthroplasty (TKA). METHODS: From June to September 2020, 94 participants were included from the Second Hospital of Tangshan and randomly assigned to the WAA group (47 cases) and the sham WAA group (47 cases) by a random number table, receiving real or sham WAA treatment, respectively. The primary outcome measure involved the visual analogue scale (VAS) scores at rest and in motion. The secondary outcomes involved the range of motion (ROM) of the knee joints, straight-leg raising time, postoperative weight-bearing time, sufentanil consumption within 48 h of patient-controlled analgesia (PCA) pump, length of hospital stay, and postoperative complications. RESULTS: The VAS scores on the 3rd, 5th, and 7th postoperative days at rest and in motion was significantly lower in the WAA group than that of the sham WAA group (P<0.01). The ROM on the 1st, 2nd, and 3rd PODs was significantly higher in the WAA group than that of the sham WAA group (P<0.01). In comparison to the sham WAA group, the sufentanil consumption within 48 h of PCA pump was significantly less in the WAA group (156.3 ± 12.2 µg vs. 128.8 ± 9.8 µg, P<0.01). There was no significant difference in active straight-leg raising time, postoperative weight-bearing time, length of hospital stay, and postoperative complications between the two groups (P>0.05). CONCLUSIONS: WAA could alleviate post-TKA pain, improve knee joint function, and reduce the sufentanil consumption within 48 h of PCA pump. WAA is a safe and effective treatment in the perioperative analgesic management for TKA.
Assuntos
Terapia por Acupuntura , Analgesia , Artroplastia do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Tornozelo , Punho , Sufentanil , Dor Pós-Operatória/terapia , Terapia por Acupuntura/efeitos adversos , Articulação do JoelhoRESUMO
BACKGROUND: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort. AIM: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD. METHODS: Eighty AECOPD patients were included in the study. The patients were in the intensive care department of our hospital from October 2019 to October 2021. The patients were divided into the control and treatment groups according to the different treatment methods with 40 patients in each group. Differences in patient comfort, blood gas analysis and infection indices were analyzed between the two groups. RESULTS: After treatment, symptoms including nasal, throat and chest discomfort were significantly lower in the treatment group compared to the control group on the 3rd and 5th days (P < 0.05). Before treatment, the PaO2, PaO2/FiO2, PaCO2, and SaO2 in the two groups of patients were not significantly different (P > 0.05). After treatment, the same indicators were significantly improved in both patient groups but had improved more in the treatment group compared to the control group (P < 0.05). After treatment, the white blood cell count, and the levels of C-reactive protein and calcitonin in patients in the treatment group were significantly higher compared to patients in the control group (P < 0.05). CONCLUSION: HFNC treatment can improve the ventilation of AECOPD patients whilst also improving patient comfort, and reducing complications. HFNC is a clinically valuable technique for the treatment of AECOPD.
RESUMO
Lactic acid bacteria (LAB) are important members in synthetic microbial consortia due to their 'generally recognized as safe' status and diverse metabolic activities. Defined communities with LAB show great potential in elucidating metabolic interactions that drive their assembly and demonstrating power to address sustainability challenges in food, environment, and health.
Assuntos
Lactobacillales , Consórcios Microbianos , Lactobacillales/genética , Biologia SintéticaRESUMO
This study is to investigate the transportation of scutellarin in cell and live models and study on mechanism of absorption and transport of scutellarin in mouse liver. The concentration of scutellarin in plasma and liver from control and pretreated groups was determined by high performance liquid chromatography. The uptake of scutellarin was examined in control hepatocytes group, induced hepatocytes group and induced hepatocytes plus pravastatin group. Pravastatin can affect the pharmacokinetics of scutellarin in mouse: CL is decreased while AUC is increased. The scutellarin absorption of hepatocyte induced group was higher than that of control group, but was decreased in the group with pravastatin added. The research showed that there was potential drug interaction between pravastatin and scutellarin. The drugs may compete for oatp2 mediated transport pathway consisted in the uptake of scutellarin in liver.
Assuntos
Apigenina/farmacocinética , Glucuronatos/farmacocinética , Hepatócitos/metabolismo , Pravastatina/farmacologia , Absorção , Animais , Apigenina/sangue , Apigenina/metabolismo , Área Sob a Curva , Transporte Biológico , Sobrevivência Celular , Cromatografia Líquida de Alta Pressão/métodos , Interações Medicamentosas , Glucuronatos/sangue , Glucuronatos/metabolismo , Hepatócitos/citologia , Fígado/metabolismo , Masculino , Camundongos , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Pravastatina/metabolismo , Carbonitrila de Pregnenolona/farmacologia , Distribuição AleatóriaRESUMO
Due to the shortage of phosphate and the eutrophication caused by phosphorus pollution, it is urgent to recover phosphate from wastewater. Given their high adsorption capacity and convenient separation from water to which a magnetic field is applied, ferrite composites have received increasing attention for phosphate recovery. In this study, Spinel La@MgFe2O4 was prepared using a one-step co-precipitation method. La3+ loading on grain boundary defects of MgFe2O4, and phosphorus absorption capacity were examined using X-ray diffraction (XRD), Fourier-transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), and vibrating sample magnetometry (VSM). The structure of La@MgFe2O4 involved La3+ loading on grain boundary defects of MgFe2O4 in the form of La(OH)3. The addition of La changed the crystallinity and morphology of MgFe2O4, which greatly improved the capacity of MgFe2O4 for phosphorus adsorption. Saturation magnetization remained at 14 emu·g-1, which was easily separated from water using an external magnetic field. The maximum adsorption capacity was 143.156 mg·g-1 at pH 6 and 10â, which was comparable to that achieved at 25â. Kinetic observations showed that a low phosphorus concentration (10 mg·L-1) could result in extremely low phosphorus adsorption by La@MgFe2O4 after 30 min. The adsorption mechanism shows that phosphorus is removed through ligand exchange and the formation of inner spherical complexes. La@MgFe2O4 has highly selective adsorption with respect to phosphate, and the adsorbent can be reused many times after desorption. Based on addition of 1 g·L-1 of La@MgFe2O4 in the treatment of low temperature municipal wastewater in Northern China, phosphate concentrations could be reduced to less than 0.5 mg·L-1 an hour, offering a promising means of phosphate adsorption even in cold regions.
RESUMO
OBJECTIVE: To observe the effect of transcutaneous electric acupoints stimulation (TEAS) on vascular endothelial function and inflammatory factors after percutaneous coronary intervention (PCI) in patients. METHODS: A total of 94 patients with coronary heart disease and undergoing PCI were randomized into a TEAS group and a sham-TEAS group, 47 cases in each one. In the TEAS group, TEAS started at unilateral Neiguan (PC6) and Ximen (PC4) 30 min before PCI till the end of PCI. In the sham-TEAS group, the procedure and persistent time were same as the TEAS group, but no electric stimulation was performed. Before treatment and at 8 h and 24 h after PCI, the levels of serum endothelin-1 (ET-1), von Willebrand factor (vWF), nitric oxide (NO), blood flow dependent diastolic function (FMD), interleukin-6 (IL-6), inteleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9) and high-sensitivity C-reactive protein (hs-CRP) were detected in the patients successively. RESULTS: Compared with the levels before PCI, the levels of ET-1 and vWF were all increased at 8 h and 24 h after PCI in the two groups (P<0.05) and the levels in the TEAS group were remarkably lower than those in the sham-TEAS group (P<0.05). Compared with the levels before PCI, the levels of NO and FMD at 8 h and 24 h after PCI were all reduced in the two groups (P<0.05) and the levels in the TEAS group were higher obviously than those in the sham-TEAS group (P<0.05). Compared with the levels before PCI, the levels of hs-CRP, MMP-9, IL-6 and IL-10 were all increased at 8 h and 24 h after PCI in the two groups (P<0.05); Compared with the sham-TEAS group, the levels of hs-CRP, MMP-9 and IL-6 were reduced and the level of IL-10 was increased at 8 h and 24 h after PCI in the TEAS group (P<0.05). CONCLUSION: TEAS effectively improves the vascular endothelial function and reduces serum inflammatory factors after PCI.
Assuntos
Doença das Coronárias , Intervenção Coronária Percutânea , Estimulação Elétrica Nervosa Transcutânea , Pontos de Acupuntura , Proteína C-Reativa , Doença das Coronárias/terapia , Humanos , Intervenção Coronária Percutânea/efeitos adversosRESUMO
OBJECTIVES: Urinary stem cells (USCs) have the capacity for unlimited growth and are promising tools for the investigations of cell differentiation and urinary regeneration. However, the limited life span significantly restricts their usefulness. This study is aimed at exploring the effect of integrin-linked kinase (ILK) on the smooth muscle cells (SMCs) differentiation of the dog USCs and investigating its molecular mechanism. METHODS: An immortalized USCs cell line with the molecular markers and biological functions was prepared. After successfully inducing the differentiation of USCs into SMCs, the expression level of the unique key factor and its mechanisms in this process was determined through real-time polymerase chain reaction, Western blot, or Immunofluorescence staining. RESULTS: We found that high cell density promoted USCs differentiation SMCs, and ILK was necessary for USCs differentiation into SMCs. Knocking down ILK decreased the expression of SMCs specific-marker, while using a selective ILK agonist increased the expression of SMCs specific-marker. Furthermore, ILK regulated SMCs differentiation in part through the activation of NF-κB pathway in USCs. A NF-κB activity assay showed overexpression of ILK could significantly upregulate NF-κB p50 expression, and NF-κB p50 acts as downstream signal molecular of ILK. CONCLUSION: High cell density induces the differentiation of USCs into SMCs, and ILK is a key regulator of myogenesis. Furthermore, NF-κB signaling pathway might play a crucial role in this process.
RESUMO
OBJECTIVE: To investigate the expression of the Chk1 gene in human sperm and its clinical significance. METHODS: We collected 80 semen samples and divided them into 4 groups of equal number: normal, oligospermia, asthenozoospermia and oligoasthenozoospermia. The Chk1 expression and its relative level were detected by Western blot and RT-PCR, sperm DNA damage and gradient changes assessed by DNA ladder analysis, and sperm apoptosis determined by Annexin V/PI double staining in each group. RESULTS: The Chk1 gene was expressed in all the four groups, but with significant differences (P < 0.01); the relative levels of CHK1 protein were similar to those of Chk1 mRNA in the normal, oligospermia, asthenozoospermia and oligoasthenozoospermia groups, which were 1.00 +/- 0.22, 0.76 +/- 0.10, 0.45 +/- 0.08 and 0.37 +/- 0.07, respectively. DNA ladder analysis showed a marked DNA ladder in the asthenozoospermia and oligoasthenozoospermia groups. Sperm apoptosis was markedly increased in the oligospermia, asthenozoospermia, oligoasthenozoospermia and 100% graded sperm groups ([ 8.3 +/- 0.60]%, [11.6 +/- 0.92]%, [12.5 +/- 1.43]% and [17.0 +/- 1.98]%), as compared with the normal group ([7.6 +/- 0.34]%) (P < 0.05). CONCLUSION: Chk1 is expressed in human sperm, but differently in different semen quality groups. And its expression is correlated with sperm DNA damage and apoptosis; its reduction may lead to declined sperm repair and increased sperm apoptosis and thus affect semen quality.
Assuntos
Proteínas Quinases/genética , Análise do Sêmen , Espermatozoides/metabolismo , Apoptose , Quinase 1 do Ponto de Checagem , Dano ao DNA , Humanos , MasculinoRESUMO
White biotechnology relies on the sophisticated chemical machinery inside living cells for producing a broad range of useful compounds in a sustainable and environmentally friendly way. However, despite the impressive repertoire of compounds that can be generated using white biotechnology, this approach cannot currently fully replace traditional chemical production, often relying on petroleum as a raw material. One challenge is the limited number of chemical transformations taking place in living organisms. Biocompatible chemistry, that is non-enzymatic chemical reactions taking place under mild conditions compatible with living organisms, could provide a solution. Biocompatible chemistry is not a novel invention, and has since long been used by living organisms. Examples include Fenton chemistry, used by microorganisms for degrading plant materials, and manganese or ketoacids dependent chemistry used for detoxifying reactive oxygen species. However, harnessing biocompatible chemistry for expanding the chemical repertoire of living cells is a relatively novel approach within white biotechnology, and it could potentially be used for producing valuable compounds which living organisms otherwise are not able to generate. In this mini review, we discuss such applications of biocompatible chemistry, and clarify the potential that lies in using biocompatible chemistry in conjunction with metabolically engineered cell factories for cheap substrate utilization, improved cell physiology, efficient pathway construction and novel chemicals production.