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1.
Int Immunopharmacol ; 96: 107580, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823430

RESUMO

Corneal lymphangiogenesis induced by macrophages played a critical role in corneal allograft rejection (CGR). However, there are few Food and Drug Administration (FDA)-approved drugs that target lymphangiogenesis. The aim of our study is to evaluate the effects of dimethyl fumarate (DMF) on corneal allograft survival in rats. Penetrating corneal transplantation was performed in rats. Subconjunctival injections of dimethyl fumarate (20 µg) were administered at the end of the operation and postoperative day 3 to day 11. The clinical signs of corneal allografts were evaluated. Immunohistochemistry, quantitative real-time PCR (qPCR), flow cytometry and western blot were performed respectively. The effects and mechanism of DMF on RAW264.7 cells were determined by qPCR, enzyme-linked immunosorbent assay (ELISA), and western blot in vitro. The results showed that subconjunctival injections of DMF could significantly inhibit corneal lymphangiogenesis and CGR with decreased corneal macrophage infiltration compared with the vehicle group. Moreover, DMF could reduce the mRNA expression of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and vascular endothelial growth factor-C (VEGF-C) in the corneal grafts and RAW264.7 macrophages by inhibiting NF-κB activation. Furthermore, compared with the vehicle group, the number of dendritic cells in the ipsilateral cervical lymph nodes of the DMF-treated group was decreased significantly. Collectively, our findings showed that DMF could suppress CGR by inhibiting the macrophage-induced corneal lymphoangiogenesis.

2.
Pharmacol Res ; 167: 105524, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33667684

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, by increasing hepatic low density lipoprotein (LDL) receptor (LDLR) levels, has emerged as a strategy to reduce atherosclerosis by lowering circulating very low density lipoprotein (VLDL)-cholesterol. We hypothesized that the therapeutic effectiveness of PCSK9 inhibition can be increased by accelerating the generation of VLDL remnants, which typically have a high affinity for the LDLR. Therefore, we aimed to investigate whether accelerating lipolytic processing of VLDL by brown fat activation can further lower (V)LDL and reduce atherosclerosis on top of PCSK9 inhibition. APOE*3-Leiden.CETP mice were fed a Western-type diet and treated with the anti-PCSK9 antibody alirocumab or saline. After 2 weeks, both groups of mice were randomized to receive either the selective ß3-adrenergic receptor (AR) agonist CL316,243 to activate brown fat or saline for 3 additional weeks to evaluate VLDL clearance or 12 additional weeks to analyze atherosclerosis development. ß3-AR agonism and alirocumab combined decreased (V)LDL-cholesterol compared to alirocumab alone, which was explained by an accelerated plasma clearance of VLDL-cholesteryl esters that were mainly taken up by the liver. In addition, the combination promoted the transfer of VLDL-phospholipids to HDL to a higher extent than alirocumab alone, accompanied by higher plasma HDL-cholesterol levels and increased cholesterol efflux capacity. Consequently, combination treatment largely reduced atherosclerotic lesion area compared to vehicle. Together, ß3-AR agonism enhances the lipoprotein-modulating effects of alirocumab to further improve dyslipidemia and non-significantly further attenuate atherosclerosis development. Our findings demonstrate that brown fat activation may enhance the therapeutic effects of PCSK9 inhibition in dyslipidemia.

3.
Environ Res ; 197: 111053, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33785327

RESUMO

Heavy metals contained in sewage sludge may cause potential environmental pollution. In this study, compound binders were used to stabilize and solidify the sludge, which aims to reduce hazard of heavy metals. The strength and leaching behavior of heavy metals from treated sludge was investigated by performing a series of laboratory experiments including the unconfined compressive strength (UCS), the toxicity characteristic leaching procedure (TCLP), the sequential chemical extraction (SCE), and the semi-dynamic leaching test (Semi-DLT). The experimental results showed that the UCS of sludge was significantly improved after stabilization and solidification (S/S) treatment, therefore it can be used as low graded material for landfill. According to the TCLP tests, the selected heavy metals (i.e. Cr, Cu, Zn, Pb, Ni) became more stable under acid conditions in short term. From the SCE tests, some heavy metals were effectively converted into stable form in S/S process. The long term leaching behavior of the heavy metals was also evaluated by the diffusion coefficients (De) and leaching index (L) calculated by the data obtained from the Semi-DLT tests. Low De values showed the S/S treatment is effective for sewage sludge, while the calculated L values also meet the environmental requirement of heavy metal stability.

4.
Sci Rep ; 11(1): 6269, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737623

RESUMO

The carbon (C) pool in forest ecosystems plays a long-term and sustained role in mitigating the impacts of global warming, and the sequestration of C is closely linked to the nitrogen (N) cycle. Accurate estimates C and N storage (SC, SN) of forest can improve our understanding of C and N cycles and help develop sustainable forest management policies in the content of climate change. In this study, the SC and SN of various forest ecosystems dominated respectively by Castanopsis carlesii and Lithocarpus mairei (EB), Pinus yunnanensis (PY), Pinus armandii (PA), Keteleeria evelyniana (KE), and Quercus semecarpifolia (QS) in the central Yunnan Plateau of China, were estimated on the basis of a field inventory to determine the distribution and altitudinal patterns of SC and SN among various forest ecosystems. The results showed that (1) the forest SC ranged from 179.58 ± 20.57 t hm-1 in QS to 365.89 ± 35.03 t hm-1 in EB. Soil, living biomass and litter contributed an average of 64.73%, 31.72% and 2.86% to forest SC, respectively; (2) the forest SN ranged from 4.47 ± 0.94 t ha-1 in PY to 8.91 ± 1.83 t ha-1 in PA. Soil, plants and litter contributed an average of 86.88%, 10.27% and 2.85% to forest SN, respectively; (3) the forest SC and SN decreased apparently with increasing altitude. The result demonstrates that changes in forest types can strongly affect the forest SC and SN. This study provides baseline information for forestland managers regarding forest resource utilization and C management.

5.
Nucleic Acids Res ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764415

RESUMO

Cas12f, also known as Cas14, is an exceptionally small type V-F CRISPR-Cas nuclease that is roughly half the size of comparable nucleases of this type. To reveal the mechanisms underlying substrate recognition and cleavage, we determined the cryo-EM structures of the Cas12f-sgRNA-target DNA and Cas12f-sgRNA complexes at 3.1 and 3.9 Å, respectively. An asymmetric Cas12f dimer is bound to one sgRNA for recognition and cleavage of dsDNA substrate with a T-rich PAM sequence. Despite its dimerization, Cas12f adopts a conserved activation mechanism among the type V nucleases which requires coordinated conformational changes induced by the formation of the crRNA-target DNA heteroduplex, including the close-to-open transition in the lid motif of the RuvC domain. Only one RuvC domain in the Cas12f dimer is activated by substrate recognition, and the substrate bound to the activated RuvC domain is captured in the structure. Structure-assisted truncated sgRNA, which is less than half the length of the original sgRNA, is still active for target DNA cleavage. Our results expand our understanding of the diverse type V CRISPR-Cas nucleases and facilitate potential genome editing applications using the miniature Cas12f.

6.
Cardiovasc Res ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33693480

RESUMO

AIMS: Fibroblast growth factor (FGF) 21, a key regulator of energy metabolism, is currently evaluated in humans for treatment of type 2 diabetes and nonalcoholic steatohepatitis. However, the effects of FGF21 on cardiovascular benefit, particularly on lipoprotein metabolism in relation to atherogenesis, remain elusive. METHODS AND RESULTS: Here, the role of FGF21 in lipoprotein metabolism in relation to atherosclerosis development was investigated by pharmacological administration of a half-life extended recombinant FGF21 protein to hypercholesterolemic APOE*3-Leiden.CETP mice, a well-established model mimicking atherosclerosis initiation and development in humans. FGF21 reduced plasma total cholesterol, explained by a reduction in non-HDL-cholesterol. Mechanistically, FGF21 promoted brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning, thereby enhancing the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT and into browned WAT, consequently accelerating the clearance of the cholesterol-enriched remnants by the liver. In addition, FGF21 reduced body fat, ameliorated glucose tolerance and markedly reduced hepatic steatosis, related to upregulated hepatic expression of genes involved in fatty acid oxidation and increased hepatic VLDL-triglyceride secretion. Ultimately, FGF21 largely decreased atherosclerotic lesion area, which was mainly explained by the reduction in non-HDL-cholesterol as shown by linear regression analysis, decreased lesion severity and increased atherosclerotic plaque stability index. CONCLUSIONS: FGF21 improves hypercholesterolemia by accelerating triglyceride-rich lipoprotein turnover as a result of activating BAT and browning of WAT, thereby reducing atherosclerotic lesion severity and increasing atherosclerotic lesion stability index. We have thus provided additional support for the clinical use of FGF21 in the treatment of atherosclerotic cardiovascular disease. TRANSLATIONAL PERSPECTIVES: Current therapeutics do not fully block atherosclerosis development, indicating a need for additional effective therapeutics. Here, we demonstrate that pharmacological treatment with recombinant FGF21 potently protects against atherosclerosis in APOE*3-Leiden.CETP mice. Mechanistically, FGF21 reduces hypercholesterolemia by accelerating triglyceride-rich lipoprotein turnover as a result of enhancing adipose tissue thermogenesis, thereby alleviating atherosclerotic lesion formation and severity. Consistent with our animal findings, FGF21 administration in obese patients has shown to reduce several cardiovascular risk factors such as obesity and dyslipidemia. Therefore, our present results, together with available clinical data, suggest that FGF21 is a promising therapeutic for atherosclerotic diseases.

7.
J Dairy Sci ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33685712

RESUMO

The elongation of long-chain fatty acid family member 6 (ELOVL6) gene plays an important role in the synthesis of long-chain saturated and monounsaturated fatty acids. Although some studies have revealed that ELOVL6 is the target of sterol regulatory element binding protein 1 (SREBP1; gene name SREBF1) in rodents, the mechanism underlying ELOVL6 regulation during lactation in dairy goats remains unknown. The present study aimed to investigate the transcriptional regulation mechanism of ELOVL6 in goat mammary epithelial cells (GMEC). We used PCR to clone and sequenced a 2,370 bp fragment of the ELOVL6 5' flanking region from goat genomic DNA. Deletion analysis revealed a core promoter region located -105 to -40 bp upstream of the transcriptional start site. Mutant sterol regulatory elements (SRE) 1 and 3 significantly reduced the ELOVL6 promoter activities in GMEC. Both SRE1 and SRE3 binding sites were required for the basal transcriptional activity of ELOVL6. Luciferase reporter assays showed that SREBF1 knockdown decreased ELOVL6 promoter activities in GMEC. Furthermore, SRE1 and SRE3 sites were simultaneously mutated completely abolished the stimulatory effect of SREBF1 and the repressive effect of linoleic acid on ELOVL6 gene promoter activities. Furthermore, chromatin immunoprecipitation assays confirmed that SREBP1 directly bound to SRE sites in the ELOVL6 promoter. In conclusion, these results indicate that SREBP1 regulates ELOVL6 transcription via the SRE elements located in the ELOVL6 promoter in goat mammary gland.

8.
Neurosci Lett ; 752: 135842, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766734

RESUMO

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

9.
J Biochem ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33751071

RESUMO

SF3B1, an essential RNA splicing factor, is frequently mutated in various types of cancers, and the cancer-associated SF3B1 mutation causes aberrant RNA splicing. The aberrant splicing of several transcripts, including MAP3K7, promotes tumorigenesis. Here, we identify a premature termination codon in the aberrantly spliced transcript of MAP3K7. Treatment of HEK293T cells transfected with the K700E-mutated SF3B1 with cycloheximide leads to increased accumulation of the aberrant spliced transcript of MAP3K7, demonstrating that the aberrantly spliced transcript of MAP3K7 is targeted by nonsense-mediated decay. The aberrantly spliced MAP3K7 transcript uses an aberrant 3' splice sites and an alternative branchpoint sequence. In addition, the aberrant splicing of MAP3K7 requires not only the polypyrimidine tract associated with normal splicing but also an alternative polypyrimidine tract upstream of the aberrant 3' splice site. Other cancer-associated SF3B1 mutations also cause the aberrant splicing of MAP3K7, which depends on the same sequence features. Our data provide a further understanding of the mechanisms underlying aberrant splicing induced by cancer-associated SF3B1 mutation, and reveal an important role of alternative polypyrimidine tract in diseases.

11.
ACS Infect Dis ; 7(3): 650-660, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33593060

RESUMO

Effective strategies are needed to deal with invasive fungal infections caused by drug-resistant fungi. Previously, we designed a series of antifungal benzocyclane derivatives based on the drug repurposing of haloperidol. Herein, further structural optimization and antifungal mechanism studies were performed, leading to the discovery of new piperidol derivative B2 with improved synergistic antifungal potency, selectivity, and water solubility. In particular, the combination of compound B2 and fluconazole showed potent in vitro and in vivo antifungal activity against azole-resistant Candida albicans. Compound B2 inhibited important virulence factors by regulating virulence-associated genes and improved the efficacy of fluconazole by down-regulating the CYP51-coding gene and efflux pump gene. Taken together, the piperidol derivative B2 represents a promising lead compound for the combinational treatment of azole-resistant candidiasis.

12.
Biochemistry ; 60(9): 663-677, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33620215

RESUMO

Structures of yeast alcohol dehydrogenase determined by X-ray crystallography show that the subunits have two different conformational states in each of the two dimers that form the tetramer. Apoenzyme and holoenzyme complexes relevant to the catalytic mechanism were described, but the asymmetry led to questions about the cooperativity of the subunits in catalysis. This study used cryo-electron microscopy (cryo-EM) to provide structures for the apoenzyme, two different binary complexes with NADH, and a ternary complex with NAD+ and 2,2,2-trifluoroethanol. All four subunits in each of these complexes are identical, as the tetramers have D2 symmetry, suggesting that there is no preexisting asymmetry and that the subunits can be independently active. The apoenzyme and one enzyme-NADH complex have "open" conformations and the inverted coordination of the catalytic zinc with Cys-43, His-66, Glu-67, and Cys-153, whereas another enzyme-NADH complex and the ternary complex have closed conformations with the classical coordination of the zinc with Cys-43, His-66, Cys-153, and a water or the oxygen of trifluoroethanol. The conformational change involves interactions of Arg-340 with the pyrophosphate group of the coenzyme and Glu-67. The cryo-EM and X-ray crystallography studies provide structures relevant for the catalytic mechanism.

13.
Psychophysiology ; : e13784, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559273

RESUMO

Congruency effect is the increase in response time when relevant and irrelevant cues indicate incongruent rather than congruent responses. The congruency effect is smaller in the trial after an incongruent trial than after a congruent trial: this difference is known as the congruency sequence effect (CSE). Psychophysical and neural studies have suggested that the lateral prefrontal cortex (LPFC) and the medial prefrontal cortex are associated with the CSE. In the present study, we applied anodal and cathodal transcranial direct current stimulation, which is thought to result in excitation and inhibition, respectively, on the LPFC, while human participants were performing a flanker task. We found that the CSE was increased under cathodal stimulation (inhibition) of the LPFC. Moreover, the LPFC stimulation modulated the congruency effect after a congruent trial. Further analyses suggested that the results cannot be explained by any of the currently prevailing hypotheses of the CSE, including the conflict monitoring hypothesis, feature integration hypothesis, and temporal learning account. Based on our findings, we propose that a new distinct mechanism might be involved in the CSE. Specifically, the LPFC might contribute to the CSE by maintaining the attention to the task-relevant information, which is an endogenous goal-oriented function and reduces the carry-over of the task-irrelevant information after a congruent trial.

14.
Nano Lett ; 21(4): 1722-1728, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33528254

RESUMO

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.

15.
Sci Total Environ ; 768: 144368, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33453541

RESUMO

The residual ciprofloxacin (CIP) in water seriously menaces the ecological safety and public health. Here, a Fe-free photo-electro-Fenton-like (PEF) system was designed for efficient degradation of CIP in water. A Z-scheme MnOx/g-C3N4 (MCN) nanocomposite with low-cost, large specific surface area and abundant active sites was successfully synthesized as a photoelectric catalyst. The XPS analysis indicated the presence of Mn2+, Mn3+ and Mn4+ in the MCN (1:6) composite, and the conversion among polyvalent manganese made the decomposition of H2O2 more efficient. Therefore, the manganese ions replaced the Fe element in traditional Fenton system. With the MCN (1:6), the PEF system could also produce O2-, OH and h+ under the visible light irradiation. The synergetic excitation of multiple active species promoted the rapid decomposition of CIP. Besides, the polyvalent property of manganese oxide resulted in the presence of oxygen vacancies which could improve the electrocatalytic reactivity of the catalyst. Finally, the degradation efficiency of CIP was 96.23% in 120 min and the mineralization efficiency was 80.02% in 240 min.


Assuntos
Ciprofloxacino , Poluentes Químicos da Água , Peróxido de Hidrogênio , Ferro , Manganês , Oxirredução , Poluentes Químicos da Água/análise
16.
Chem Commun (Camb) ; 57(7): 943-946, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33399154

RESUMO

Through precise and ingenious molecular modification, we successfully obtained a multiaxial ferroelectric, [FEtDabco]ZnI3 (N-fluoroethyl-N'-ZnI3-1,4-diazabicyclo[2.2.2]octonium), with a record high Tc (540 K) among molecular ferroelectrics, which is promising for application under extreme thermal conditions.

17.
Nat Chem Biol ; 17(4): 387-393, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33495647

RESUMO

Cas12g, the type V-G CRISPR-Cas effector, is an RNA-guided ribonuclease that targets single-stranded RNA substrate. The CRISPR-Cas12g system offers a potential platform for transcriptome engineering and diagnostic applications. We determined the structures of Cas12g-guide RNA complexes in the absence and presence of target RNA by cryo-EM to a resolution of 3.1 Å and 4.8 Å, respectively. Cas12g adopts a bilobed structure with miniature REC2 and Nuc domains, whereas the guide RNAs fold into a flipped 'F' shape, which is primarily recognized by the REC lobe. Target RNA and the CRISPR RNA (crRNA) guide form a duplex that inserts into the central cavity between the REC and NUC lobes, inducing conformational changes in both lobes to activate Cas12g. The structural insights would facilitate the development of Cas12g-based applications.

18.
Medicine (Baltimore) ; 100(1): e23823, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429743

RESUMO

BACKGROUND: Herpes zoster (HZ), is a painful skin rash disease with cutaneous symptoms and acute zoster-associated pain (ZAP). Postherpetic neuralgia (PHN), as the most frequent sequela of HZ, can persist a long time. Both HZ and PHN may significantly impact the quality of life and made great economical afford to affected patients. Its optimal treatment on HZ and PHN is still an urgent problem. In China, thermotherapy, including moxibustion and fire needle, is widely used because they can quickly promote the recovery of shingles and reduce the occurrence of PHN. Thermotherapy can also reduce pain intensity, relieve anxiety, and improve quality of life of PHN. Based on the current literatures, the effect and safety of thermotherapy will be systematically evaluated to provide appropriate complementary therapies for HZ and PHN. METHODS: Studies search for eligible randomized controlled trials (RCTs) that use thermotherapy including fire needle and moxibustion for HZ or PHN from the following databases: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine Database (CBM), Technology Periodical database (VIP), and Wanfang database. Language restrictions for retrieving literature are English and Chinese. Their data extraction will be done by 2 researchers. Mean difference (MD) or relative risk (RR) with fixed or random effect model in terms of 95% confidence interval (CI) will be adopted for the data synthesis. To evaluate the risk of bias, the Cochrane's risk of bias assessment tool will be utilized. The sensitivity or subgroup analysis will also be conducted when meeting high heterogeneity (I2 > 50%). RESULTS: This meta-analysis will provide an authentic synthesis of the thermotherapy's effect on HZ and PHN, including incidence of postherpetic neuralgia and adverse events. DISCUSSION: The findings of the review offer updated evidence and identify whether thermotherapy can be an effective treatment for HZ and PHN for clinicians. REGISTRATION NUMBER: INPLASY2020110009.


Assuntos
Protocolos Clínicos , Herpes Zoster/terapia , Hipertermia Induzida/normas , Neuralgia Pós-Herpética/terapia , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Terapia por Acupuntura/normas , Herpes Zoster/fisiopatologia , Humanos , Hipertermia Induzida/métodos , Metanálise como Assunto , Neuralgia Pós-Herpética/fisiopatologia , Revisões Sistemáticas como Assunto
19.
J Ethnopharmacol ; 266: 113421, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022337

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Irinotecan (CPT-11) is a valuable chemotherapeutic compound, but its use is associated with severe diarrhea in some patients. The CPT-11 prodrug is converted into the active 7-ethyl-10-hydroxycamptothecin (SN-38) metabolite, which can then be retained for extended periods in the intestine, leading to the onset of diarrhea and related symptoms. Banxia Xiexin Decoction (BXD) is commonly employed for the treatment of gastroenteritis in traditional Chinese medicine (TCM), and in clinical settings, it is used to prevent diarrhea in patients undergoing CPT-11 treatment. To date, however, there have been no studies specifically examining which components of BXD can alleviate the gastrointestinal symptoms associated with CPT-11 administration. AIM: This study aimed to identify the main herbal components of BXD associated with protection against CPT-11-induced intestinal toxicity in a murine model system. MATERIALS AND METHODS: SN-38 levels were measured by UPLC-ESI-MS/MS in samples collected from mice subjected to CPT-11-induced diarrhea that had been administered BXD or different components thereof. Pearson correlation and Grey relational analyses were then used to explore spectrum-effect relationships between reductions in intestinal SN-38 levels and specific chemical fingerprints in samples from mice administered particular combinations of BXD component herbs. RESULTS: We found that different herbal combinations were associated with significant differences in intestinal SN-38 reductions in treated mice. Our spectrum-effect analysis revealed that BXD components including chrysin 6-C-arabinoside-8-C-glucoside, coptisine, hydroxyl oroxylin A 7-O-glucuronide (hydroxyl wogonoside), baicalin, an isomer of 5,6,7-trihydroxyl-flavanone-7-O-glucuronide, berberine, palmatine, and chrysin-7-O-glucuronide were all directly linked with reductions in intestinal SN-38 levels. We therefore speculate that these compounds are the primary bioactive components of BXD, suggesting that they offer protection against CPT-11-induced diarrhea. CONCLUSION: By utilizing UPLC to analyze SN-38 levels in mice treated with a variety of herbal combinations, we were able to effectively explore BXD spectrum-effect relationships and to thereby establish the components of this medicinal preparation that were bioactive and capable of preventing CPT-11-induced diarrhea in mice. This and similar spectrum-effect studies represent a robust means of exploring the mechanistic basis for the pharmacological activity of TCM preparations.


Assuntos
Diarreia/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Enteropatias/prevenção & controle , Irinotecano/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Diarreia/induzido quimicamente , Medicamentos de Ervas Chinesas/química , Feminino , Enteropatias/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Espectrometria de Massas em Tandem , Inibidores da Topoisomerase I/toxicidade
20.
Talanta ; 223(Pt 2): 121741, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33298267

RESUMO

A novel fluorometric strategy is proposed for detecting curcumin by polyvinyl pyrrolidone-templated Cu NCs (PVP-Cu NCs) as a fluorescent probe which exhibits excitation/emission peaks at 380/510 nm. The fluorescent excitation and emission spectra of PVP-Cu NCs have a striking overlap with the UV-vis spectrum of curcumin, and the fluorescence lifetime of PVP-Cu NCs decreases after the addition of curcumin. Curcumin leads to fluorescence quenching based on fluorescence resonance energy transfer. This method allows for the determination of curcumin in the range of 0.1-10 µg mL-1 and the detection limit is 21 ng mL-1. Furthermore, this method displays good selectivity and is successfully applied for real sample analysis.

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