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The polysaccharides from Stemona tuberosa Lour, a kind of plant used in Chinese herbal medicine, have various pharmacological activities, such as anti-inflammatory and antioxidant properties. However, the effects of the extraction methods and the activity of polysaccharides from different parts are still unknown. Therefore, this study aimed to evaluate the effects of different extraction methods on the yields, chemical compositions, and bioactivity of polysaccharides extracted from different parts of Stemona tuberosa Lour. Six polysaccharides were extracted from the leaves, roots, and stems of Stemona tuberosa Lour through the use of hot water (i.e., SPS-L1, SPS-R1, and SPS-S1) and an ultrasound-assisted method (i.e., SPS-L2, SPS-R2, and SPS-S2). The results showed that the physicochemical properties, structural properties, and biological activity of the polysaccharides varied with the extraction methods and parts. SPS-R1 and SPS-R2 had higher extraction yields and total sugar contents than those of the other SPSs (SPS-L1, SPS-L2, SPS-S1, and SPS-S2). SPS-L1 had favorable antioxidant activity and the ability to downregulate MUC5AC expression. An investigation of the anti-inflammatory properties showed that SPS-R1 and SPS-R2 had greater anti-inflammatory activities, while SPS-R2 demonstrated the strongest anti-inflammatory potential. The results of this study indicated that SPS-L1 and SPS-L2, which were extracted from non-medicinal parts, may serve as potent natural antioxidants, but further study is necessary to explore their potential applications in the treatment of diseases. The positive anti-inflammatory effects of SPS-R1 and SPS-R2 in the roots may be further exploited in drugs for the treatment of inflammation.
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Stemonaceae , Stemonaceae/química , Stemonaceae/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismoRESUMO
Synthetic biology is an effective way to activate silent biosynthetic gene clusters. Five new indole diterpenoids (1, 2, 5, 9, and 10), together with 10 known derivatives (3, 4, 6-8, and 11-15) were activated from Aspergillus oryzae transformants by an exogenous P450 gene Ast B and obtained under the guidance of molecular networking. Their planar structures were determined by NMR and HR-ESI-MS. The absolute configuration of compound 1 was determined by single crystal X-ray diffraction, and those of compounds 2, 5 , 9, and 10 were confirmed by comparing the observed ECD with the calculated ECD. HPLC analysis suggested that the BGCs of indole diterpenoids in A. oryzae were activated by exogenous P450 gene Ast B. Compounds 1-4, 7, 8, and 11 displayed strong activity against chloroquine-sensitive plasmodium strain P.f.3D7 with IC50 values ranging from 0.84 to 2.9 µM. It is the first report that indole diterpenoids have potential antimalarial activity. The structure-activity relationship study showed that the linear indole diterpenoids contribute significantly to the antiparasite activity. Molecular docking studies showed that 1 and positive control chloroquine were at the center of the active pocket of PfHsp90, while 11 was far from the active site.
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Aspergillus oryzae , Diterpenos , Plasmodium , Aspergillus oryzae/genética , Simulação de Acoplamento Molecular , Diterpenos/farmacologia , Diterpenos/química , Indóis/química , Cloroquina , Estrutura MolecularRESUMO
Seven new polyketides, including four indenone derivatives, cytoindenones A-C (1, 3-4), 3'-methoxycytoindenone A (2), a benzophenone derivative, cytorhizophin J (6), and a pair of tetralone enantiomers, (±)-4,6-dihydroxy-5-methoxy-α-tetralone (7), together with a known compound (5) were obtained from the endophytic fungus Cytospora heveae NSHSJ-2 isolated from the fresh stem of the mangrove plant Sonneratia caseolaris. Compound 3 represented the first natural indenone monomer substituted by two benzene moieties at C-2 and C-3. Their structures were determined by the analysis of 1D and 2D NMR, as well as mass spectroscopic data, and the absolute configurations of (±)-7 were determined on the basis of the observed specific rotation value compared with those of the tetralone derivatives previously reported. In bioactivity assays, compounds 1, 4-6 showed potent DPPH· scavenging activities, with EC50 values ranging from 9.5 to 16.6 µM, better than the positive control ascorbic acid (21.9 µM); compounds 2-3 also exhibited DPPH· scavenging activities comparable to ascorbic acid.
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Ascomicetos , Tetralonas , Antioxidantes/farmacologia , Ascomicetos/química , Benzofenonas/farmacologia , Ácido Ascórbico , Estrutura MolecularRESUMO
The synthetic biology approach enables efficient and directional mining of target compounds during drug discovery. Ten new asperterpenoids (6-15) and five known analogues (1-5), possessing a rare 5/7/3/6/5 skeleton, were obtained from two Aspergillus oryzae transformants with heterologous expression of a terpene cyclase gene AstC with one or two P450 genes AstB/A under the guidance of molecular networking. Their planar structures were determined by 1D and 2D NMR and HR-ESI-MS. The absolute configurations of compounds 6 and 9-13 were determined by single crystal X-ray diffraction, and those of compounds 7-8 and 14-15 were compared with the ECD of known compounds. Seven of all the compounds are the first asperterpenoid oxidation products at C-17 or at C-25. In bioassay, compounds 1-2, 4-5, and 6-8 displayed moderate to strong eliminating activities against chloroquine-sensitive strain (P.f.3D7) with EC50 values ranging from 2.1 to 19.3 µM. The structure-activity relationship (SAR) was discussed, which showed that substituents at C-3, C-11, C-17, C-18, and C-23 of asperterpenoids significantly affected anti-plasma parasite activity.
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Antimaláricos , Aspergillus oryzae , Aspergillus oryzae/genética , Sesterterpenos/farmacologia , Sesterterpenos/química , Antimaláricos/farmacologia , Antimaláricos/química , Relação Estrutura-Atividade , Cristalografia por Raios X , Estrutura MolecularRESUMO
Two new compounds 5-[4'-(4â³-hydroxybenzyl)-3'-hydroxybenzyloxymethyl]-furan-2-carbaldehyde (1) and 5-[4'-(4â³-hydroxybenzyl)-3'-hydroxybenzyl]-furan-2-carbal-dehyde (2), together with two known 5-(4-hydroxbenzyloxymethyl)-furan-2-carbaldehyde] (3) and 5-(hydroxymethyl)-2-furaldehyde (4), were isolated from the rhizome of Gastrodia elata. Their structures were elucidated by spectroscopic analysis and comparison of their spectral data with those reported previously. All compounds exhibited weak or no cytotoxicity against human colon carcinoma cell line (HT-29) and human chronic myelogenous leukemia cell line (K-562).
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Medicamentos de Ervas Chinesas/isolamento & purificação , Furaldeído/análogos & derivados , Gastrodia/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Furaldeído/química , Furaldeído/isolamento & purificação , Furaldeído/farmacologia , Células HT29 , Humanos , Estrutura Molecular , Fenóis/química , Rizoma/químicaRESUMO
Objective: Hepatocellular carcinoma (HCC) is a highly lethal cancer with significant mortality, primarily attributed to metastasis. Although Protocadherin Gamma Subfamily A, 9 (PCDHGA9) has been identified as a tumor suppressor gene in cancer metastasis, its role in HCC remains ambiguous. This study aims to clarify the role of PCDHGA9 in HCC by examining its expression, clinical significance, and molecular activities. Methods: Tissue microarray immunofluorescence analysis evaluated the expression of PCDHGA9 and its clinical relevance. In vitro experiments involved manipulating PCDHGA9 levels in SK-HEP-1 cells to assess migration through wound-healing and transwell assays. In vivo, shPCDHGA9 cell injections were utilized to observe effects on tumor growth and metastasis. Protein analysis and Western Blot validated epithelial-mesenchymal transition (EMT)-related proteins. Subsequent to TGF-ß treatment, cell proliferation and apoptosis were quantified using Cell counting kit-8 and flow cytometry, respectively, followed by investigation of TGF-ß effects on PCDHGA9 N6-methyladenosine (m6A) modification via Methylated RNA immunoprecipitation, RT-qPCR, and Western blot analysis. Results: Downregulation of PCDHGA9 expression in HCC tissues is correlated with poor prognosis. In vitro experiments demonstrated that modulating PCDHGA9 expression influenced HCC cell migration. In vivo, PCDHGA9 knockdown is correlated with increased metastasis. Furthermore, TGF-ß stimulation promoted cell proliferation and inhibited apoptosis. Mechanistically, TGF-ß-mediated m6A modification led to PCDHGA9 decay, promoting EMT in HCC cells. Conclusion: PCDHGA9 serves as a potential tumor suppressor in HCC by inhibiting EMT. During this process, TGF-ß is observed to exert regulatory control over m6A modifications of PCDHGA9.
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Schizophyllum commune, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (1-8) and one new meroterpenoid schizomycin I (9) together with three known analogues (10-12) were isolated from fruiting bodies of S. commune. Their planar structures were established by extensive spectroscopic and mass spectrometric data. The absolute configurations of compounds 1, 2, and 4 were determined by single crystal X-ray diffraction, and compounds 3 and 5-9 were confirmed by electronic circular dichroism calculations. Anti-inflammatory activities of all isolated compounds were evaluated for their inhibitory effects on IL-6 and IL-1ß production in RAW 264.7 cells. Among them, compound 7 exhibited significant IL-6 inhibitory activity with an IC50 value of 3.6 µM. The results of molecular docking showed that compound 7 interacts with amino acid residues (Gly117, Lys118, Asp120, Thr166, and Try168) of the IL-6 receptor protein through hydrogen bonding.
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Ascomicetos , Schizophyllum , Sesquiterpenos , Schizophyllum/química , Schizophyllum/metabolismo , Interleucina-6/metabolismo , Simulação de Acoplamento Molecular , Dicroísmo Circular , Carpóforos , Sesquiterpenos/metabolismo , Estrutura MolecularRESUMO
Psoriasis is a chronic autoimmune disease that badly affects the life quality of patients and their families. Inadequate efficacy, safety risks, high cost and low compliance of current psoriasis drugs urge development of novel small molecular drugs. In this study, two series of 37 novel compounds were designed and synthesized as inhibitors of phosphodiesterase 4 (PDE4) that specifically hydrolyzes second messenger cAMP and is an effective target for treatment of inflammatory diseases. Comprehensive structural-activity optimization led to finding of inhibitor 2e with IC50 = 2.4 nM for PDE4D and >4100-fold selectivity over other PDE families. Compound 2e inhibited the release of TNF-α (IC50 = 21.36 µM) and IL-6 (IC50 = 29.22 µM) in the LPS-stimulated Raw264.7 cells. Topical application of 2e exhibited remarkable therapeutic efficacy in imiquimod-induced psoriasis mice model, suggesting that 2e is a strong drug candidate for treatment of psoriasis.
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The root of Stemona tuberosa Lour has been used to treat tuberculosis, scabies, and eczema. Polysaccharides are among its main bioactive ingredients. A low-molecular-weight (1819 Da) polysaccharide (SPS2-A) was obtained from the root of S. tuberosa Lour by optimizing three-phase partitioning, purified using an ion chromatography column, and its effects and mechanisms were investigated. Structural analysis revealed that SPS2-A contained arabinose, galactose (Gal), glucose (Glc), xylose, and mannose. The SPS2-A backbone structure comprised sugar residues â4)-α-D-Glcp-(1â, â4)-α-D-Galp-(1â, and â4,6)-ß-D-Galp-(1â, while the side chain primarily comprised α-D-Glcp-(1 â connected to the O-6 position of the residue â4,6)-ß-D-Galp-(1â. In vitro, SPS2-A downregulated the expression of interleukin-6 in lipopolysaccharide-induced RAW264.7 macrophages. In vivo, SPS2-A significantly downregulated the expression of myeloperoxidase, interleukin-6, interleukin-1ß, and tumor necrosis factor-α in bronchoalveolar lavage fluid and lung tissue. Western blotting analysis indicated that SPS2-A reduced lung inflammation in mice with sepsis-induced acute lung injury by activating the nuclear factor κB pathway. These results suggest that SPS2-A is a potential anti-inflammatory candidate for the treatment of sepsis-induced acute lung injury.
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A series of diaryl heterocyclic analogues were designed and synthesized as tubulin polymerization inhibitors. Among them, compound 6y showed the highest antiproliferative activity against HCT-116 colon cancer cell line with an IC50 values of 2.65 µM. Compound 6y also effectively inhibited tubulin polymerization in vitro (IC50 of 10.9 µM), and induced HCT-116 cell cycle arrest in G2/M phase. In addition, compound 6y exhibited high metabolic stability on human liver microsomes (T1/2 = 106.2 min). Finally, 6y was also effective in suppressing tumor growth in a HCT-116 mouse colon model without apparent toxicity. Collectively, these results suggest that 6y represents a new class of tubulin inhibitors deserving further investigation.
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Antineoplásicos , Tubulina (Proteína) , Animais , Camundongos , Humanos , Tubulina (Proteína)/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Polimerização , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Moduladores de Tubulina/farmacologia , Antineoplásicos/farmacologiaRESUMO
Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Animais , Camundongos , Lipopolissacarídeos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Inflamação , Citocinas , Modelos Animais de DoençasRESUMO
Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.
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Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS. Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37-73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications. Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61-0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82-1.16). Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins.
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Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.
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The most commonly used oscillometric upper-arm (UA) blood pressure (BP) monitors are not convenient enough for ambulatory BP monitoring, given the large size of the arm cuff and the compression of UA during the measurement. Finger-worn oscillometric BP devices featuring miniaturized finger cuff have been developed and researched as an alternative solution to the UA-based measurement, yet the reliability of the finger-based measurement is still questioned. To investigate the feasibility of oscillometric BP measurements at the finger position, we performed model-based analysis and experimental validation to explore the underlying issues associated with extending the cuff-based oscillometric approach from UA to other alternative sites. The simulation results revealed that a larger bone-to-tissue volume ratio produced a lower pressure transmission efficiency, which can account for the inter-site measurement discrepancies of mean blood pressure (MBP). We also experimentally compared the oscillometric MBP measurements at UA, middle forearm, wrist, finger proximal phalanx, and finger distal phalanx (FD) of 20 young adults, and each position was matched with a cuff of appropriate size and kept at the same height with the heart. The experimental results demonstrated that FD could be a superior alternative position for oscillometric BP measurement, as it requires the smallest cuff size while providing the most consistent MBP with the UA. Our analysis also suggested that further study is demanded to identify the appropriate oscillometric algorithm for reliable systolic blood pressure and diastolic blood pressure measurements at FD.
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Determinação da Pressão Arterial/instrumentação , Dedos/fisiologia , Modelos Biológicos , Oscilometria/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The importance of home blood pressure (BP) monitoring has been emphasized for achieving effective hypertension management. Currently, the most popular non-invasive BP monitors for home use are the upper-arm cuff-style oscillometric devices which determine BP from the cuff pressure oscillations during the cuff inflation/deflation induced by the pulsatile blood flow in the compressed arteries. However, the large size of the upper-arm cuff is not favorable for attachment in daily life for ambulatory BP monitoring. Therefore, the miniaturization of home BP monitors is in demand to improve their portability for frequent measurements. This work examined the oscillometric measurement of mean blood pressure(MBP) at upper arm (UA), middle forearm (MA), wrist (WR), finger proximal phalanx (FP) and finger distal phalanx (FD) on 14 young adults. The experimental results showed that the mean and standard deviation of the differences between the oscillometric MBP at UA and the other sites are 8.86±6.28 mm Hg at MA, 14.43±5.52 mm Hg at WR, 9.80±6.57 mm Hg at FP and -0.77±6.37 mm Hg at FD, respectively. Based on hand checking and literature data, the order of the ratios of the bone volume to the surrounding tissue volume from large to small is WR>MA≈FP>FD≈UA. Together with the experimental results, we infer that a larger bone-tissue volume ratio could result in a larger oscillometric MBP reading. Since the applied cuff pressure are supposed to be less effectively absorbed by the soft-tissue surrounding a larger rigid bone, it is more difficult to occlude the arteries buried in the pressure-absorbing tissue at a bonier site by the inflatable cuffs, which leads to a higher measured MBP than the real MBP. In conclusion, it is promising to develop the finger oscillometric BP monitors to be worn on the finger distal phalanx which have a compact size and provide consistent measurement results with the UA measurements.
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Determinação da Pressão Arterial , Pressão Sanguínea , Monitores de Pressão Arterial , Oscilometria , EsfigmomanômetrosRESUMO
The large fragment of DNA polymerase I from Geobacillus stearothermophilus GIM1.543 (Bst DNA polymerase) with 5'-3' DNA polymerase activity while in absence of 5'-3' exonuclease activity possesses high thermal stability and polymerase activity. Bst DNA polymerase was employed in isothermal multiple self-matching initiated amplification (IMSA) which amplified the interest sequence with high selectivity and was widely applied in the rapid detection of human epidemic diseases. However, the detailed information of commercial Bst DNA polymerase is unpublished and well protected by patents, which makes the high price of commercial kits. In this study, wild-type Bst DNA polymerase (WT) and substitution mutations for improving the efficiency of DNA polymerization were expressed and purified in E. coli. Site-directed substitutions of four conserved residues (Gly310, Arg412, Lys416, and Asp540) in the activity site of Bst DNA polymerase influenced efficiency of polymerizing dNTPs. The substitution of residue Gly310 by alanine or leucine and residue Asp540 by glutamic acid increased the efficiency of polymerase activity. All mutants with higher polymerizing efficiency were employed to complete the rapid detection of EV71-associated hand, foot, and mouth disease (HFMD) by IMSA approach with relatively shorter period which is suitable for the primary diagnostics setting in rural and underdeveloped areas.
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DNA Polimerase I/metabolismo , Geobacillus/enzimologia , Mutagênese Sítio-Dirigida/métodos , Domínio Catalítico , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , DNA Polimerase I/isolamento & purificação , Eletroforese em Gel de Poliacrilamida , Cinética , Mutação/genética , Plasmídeos/genética , Reação em Cadeia da Polimerase , Recombinação GenéticaRESUMO
Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions.
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Subpopulações de Linfócitos B/imunologia , Linfócitos B Reguladores/imunologia , Proteínas de Choque Térmico/imunologia , Animais , Antígenos CD19/imunologia , Antígeno B7-H1/biossíntese , Antígeno B7-H1/imunologia , Chaperona BiP do Retículo Endoplasmático , Ensaio de Imunoadsorção Enzimática , Proteína Ligante Fas/biossíntese , Proteína Ligante Fas/imunologia , Citometria de Fluxo , Imunofluorescência , Interleucina-10/biossíntese , Interleucina-10/imunologia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The molecular subsets of glioma behave in biologically distinct ways. The present study detected isocitrate dehydrogenase (IDH) 1 and IDH2 mutations in glioma to analyze whether IDH-mutated gliomas are situated in certain preferential areas and to investigate their correlation with magnetic resonance imaging (MRI) characteristics. A series of 193 patients with astrocytic neoplasms (111 diffuse and 82 anaplastic astrocytomas), grouped according to prelabeled anatomical structures and the risk of surgery, were retrospectively reviewed for IDH1 and IDH2 mutations to compare the tumor location and MRI features. A total of 111 IDH1 mutations at codon 132 (57.5%) and six IDH2 mutations at codon 172 (3.1%) were detected. The IDH1/2 mutations were found to predict longer survival, independent of the histological type in this series of patients. The IDH-mutated gliomas were predominantly located in a single lobe, such as the frontal lobe, temporal lobe or cerebellum and rarely in the diencephalon or brain stem. Furthermore, according to the risk of surgery, the IDH-mutated tumors were rarely located in the high-risk regions of the brain, where surgery exhibits a high mortality rate intraoperatively and postoperatively. In addition, gliomas with IDH mutations were significantly more likely to exhibit a unilateral pattern of growth, sharp tumor margins, homogeneous signal intensity and less contrast enhancement on MRI. The results of the current study suggested that the prolonged survival of patients with IDH-mutated gliomas is primarily due to a less aggressive biological behavior according to tumor site and MRI features.
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1α-acetoxy-5α, 7ß-dihydroxycassa-11,13(15)-diene-16,12-lactone, a new cassane-type diterpene was isolated from Caesalpinia crista. The structure of this compound was elucidated by analysis of NMR spectra, and the relative configuration was established by NOE experiment. The new compound was evaluated for antitumour activity against T47D, DU145 and showed significant inhibitory activities.