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1.
Plant Physiol ; 194(4): 2249-2262, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38109500

RESUMO

Desiccation is typically fatal, but a small number of land plants have evolved vegetative desiccation tolerance (VDT), allowing them to dry without dying through a process called anhydrobiosis. Advances in sequencing technologies have enabled the investigation of genomes for desiccation-tolerant plants over the past decade. However, a dedicated and integrated database for these valuable genomic resources has been lacking. Our prolonged interest in VDT plant genomes motivated us to create the "Drying without Dying" database, which contains a total of 16 VDT-related plant genomes (including 10 mosses) and incorporates 10 genomes that are closely related to VDT plants. The database features bioinformatic tools, such as blast and homologous cluster search, sequence retrieval, Gene Ontology term and metabolic pathway enrichment statistics, expression profiling, co-expression network extraction, and JBrowser exploration for each genome. To demonstrate its utility, we conducted tailored PFAM family statistical analyses, and we discovered that the drought-responsive ABA transporter AWPM-19 family is significantly tandemly duplicated in all bryophytes but rarely so in tracheophytes. Transcriptomic investigations also revealed that response patterns following desiccation diverged between bryophytes and angiosperms. Combined, the analyses provided genomic and transcriptomic evidence supporting a possible divergence and lineage-specific evolution of VDT in plants. The database can be accessed at http://desiccation.novogene.com. We expect this initial release of the "Drying without Dying" plant genome database will facilitate future discovery of VDT genetic resources.


Assuntos
Briófitas , Dessecação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Genoma de Planta/genética , Transcriptoma/genética , Briófitas/genética
2.
Plant J ; 113(1): 75-91, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36416176

RESUMO

Soloist is a member of a distinct and small subfamily within the AP2/ERF transcriptional factor family that play important roles in plant biotic and abiotic stress responses. There are limited studies of Soloist genes and their functions are poorly understood. We characterized the abiotic and biotic stress tolerance function of the ScSoloist gene (designated as ScAPD1-like) from the desert moss Syntrichia caninervis. ScAPD1-like responded to multiple abiotic, biotic stresses and plant hormone treatments. ScAPD1-like protein located to the nucleus and bound to several DNA elements. Overexpression of ScAPD1-like in Arabidopsis did not alter abiotic stress resistance or inhibit Pseudomonas syringae pv. tomato (Pst) DC3000 infection. However, overexpression of ScAPD1-like significantly increased the resistance of transgenic Arabidopsis and S. caninervis to Verticillium dahliae infection, decreased reactive oxygen species accumulation and improved reactive oxygen species scavenging activity. ScAPD1-like overexpression plants altered the abundance of transcripts for lignin synthesis and promoted lignin accumulation in Arabidopsis. ScAPD1-like directly bind to RAV1, AC elements, and TATA-box in the promoters of AtPAL1 and AtC4H genes, respectively, in vitro. Chromatin immunoprecipitation-quantitative polymerase chain reaction assays demonstrated ScAPD1-like directly bound to PAL and C4H genes promoters in Arabidopsis and their homologs in S. caninervis. In S. caninervis, ScAPD1-like overexpression and RNAi directly regulated the abundance of ScPAL and ScC4H transcripts and modified the metabolites of phenylpropanoid pathway. We provide insight into the function of Soloist in plant defense mechanisms that likely occurs through activation of the phenylpropanoid biosynthesis pathway. ScAPD1-like is a promising candidate gene for breeding strategies to improve resistance to Verticillium wilt.


Assuntos
Arabidopsis , Ascomicetos , Briófitas , Bryopsida , Verticillium , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Lignina/metabolismo , Melhoramento Vegetal , Briófitas/metabolismo , Bryopsida/genética , Ascomicetos/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Resistência à Doença/genética , Doenças das Plantas/genética , Gossypium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Int J Cancer ; 154(12): 2031-2042, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38500385

RESUMO

Tumor-associated myeloid cells (TAMCs) play a crucial role in orchestrating the dynamics of the tumor immune microenvironment. This heterogeneous population encompasses myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells, all of which contribute to the establishment of an immunosuppressive milieu that fosters tumor progression. Tumor-derived exosomes (TEXs), small extracellular vesicles secreted by tumor cells, have emerged as central mediators in intercellular communication within the tumor microenvironment. In this comprehensive review, we explore the intricate mechanisms through which TEXs modulate immune-suppressive effects on TAMCs and their profound implications in cancer progression. We delve into the multifaceted ways in which TEXs influence TAMC functions, subsequently affecting tumor immune evasion. Furthermore, we elucidate various therapeutic strategies aimed at targeting TEX-mediated immune suppression, with the ultimate goal of bolstering antitumor immunity.


Assuntos
Exossomos , Células Supressoras Mieloides , Neoplasias , Humanos , Exossomos/patologia , Neoplasias/patologia , Terapia de Imunossupressão , Células Mieloides , Microambiente Tumoral
4.
Pharmacogenet Genomics ; 34(4): 126-129, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38359166

RESUMO

Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk ( P  > 0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis ( P  = 0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Peptídeos e Proteínas de Sinalização Intracelular , Doenças Musculoesqueléticas , Variantes Farmacogenômicos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Estudo de Associação Genômica Ampla , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/induzido quimicamente , Polimorfismo de Nucleotídeo Único/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
5.
Cell Commun Signal ; 22(1): 149, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402193

RESUMO

Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.


Assuntos
Apoptose , Imunidade Inata , Humanos , Piroptose , Inflamação , Citoplasma
6.
Acta Biochim Biophys Sin (Shanghai) ; 56(1): 1-14, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38105650

RESUMO

TP53, functioning as the keeper of the genome, assumes a pivotal function in the inhibition of tumorigenesis. Recent studies have revealed that p53 regulates ferroptosis pathways within tumor cells and is closely related to tumorigenesis. Therefore, we summarize the pathways and mechanisms by which p53 regulates ferroptosis and identify a series of upstream and downstream molecules involved in this process. Furthermore, we construct a p53-ferroptosis network centered on p53. Finally, we present the progress of drugs to prevent wild-type p53 (wtp53) degeneration and restore wtp53, highlighting the deficiencies of drug development and the prospects for p53 in cancer treatment. These findings provide novel strategies and directions for future cancer therapy.


Assuntos
Ferroptose , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ferroptose/genética , Carcinogênese
7.
Plant Cell Physiol ; 64(11): 1419-1432, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37706231

RESUMO

Desiccation-tolerant (DT) plants can survive extreme dehydration and tolerate the loss of up to 95% of their water content, making them ideal systems to determine the mechanism behind extreme drought stress and identify potential approaches for developing drought-tolerant crops. The desert moss Syntrichia caninervis is an emerging model for extreme desiccation tolerance that has benefited from high-throughput sequencing analyses, allowing identification of stress-tolerant genes; however, its metabolic response to desiccation is unknown. A liquid chromatography-mass spectrometry analysis of S. caninervis at six dehydration-rehydration stages revealed 912 differentially abundant compounds, belonging to 93 metabolic classes. Many (256) metabolites accumulated during rehydration in S. caninervis, whereas only 71 accumulated during the dehydration period, in contrast to the pattern observed in vascular DT plants. During dehydration, nitrogenous amino acids (l-glutamic acid and cysteinylglycine), alkaloids (vinleurosine) and steroids (physalin D) accumulated, whereas glucose 6-phosphate decreased. During rehydration, γ-aminobutyric acid, glucose 6-phosphate and flavonoids (karanjin and aromadendrin) accumulated, as did the plant hormones 12-oxo phytodienoic acid (12-OPDA) and trans-zeatin riboside. The contents ofl-arginine, maltose, turanose, lactulose and sucrose remained high throughout dehydration-rehydration. Syntrichia caninervis thus accumulates antioxidants to scavenge reactive oxygen species, accumulating nitrogenous amino acids and cytoprotective metabolites and decreasing energy metabolism to enter a protective state from dehydration-induced damage. During subsequent rehydration, many metabolites rapidly accumulated to prevent oxidative stress and restore physiological activities while repairing cells, representing a more elaborate rehydration repair mechanism than vascular DT plants, with a faster and greater accumulation of metabolites. This metabolic kinetics analysis in S. caninervis deepens our understanding of its dehydration mechanisms and provides new insights into the different strategies of plant responses to dehydration and rehydration.


Assuntos
Briófitas , Bryopsida , Desidratação , Bryopsida/genética , Hidratação , Aminoácidos , Fosfatos , Glucose
8.
Bioorg Med Chem ; 84: 117261, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-37011446

RESUMO

Targeting PI3Kγ would be a useful strategy for treating inflammatory and cancer diseases. However, the development of selective inhibitors of PI3Kγ is very challenging due to the high structural and sequence homology with other PI3K isoforms. A series of quinazolinone derivatives were designed, synthesized and biologically evaluated as PI3Kγ-selective inhibitors. Among all the 28 compounds, compound 9b was found to be the most potent selective inhibitor with IC50 values of 13.11 nM against PI3Kγ kinase. Additionally, compound 9b could generate toxicity on leukemia cells in a panel of 12 different of cancer cell lines with the IC50 value of 2.41 ± 0.11 µM on Jurkat cell. Preliminary mechanism studies indicated that compound 9b through inhibit the activity of PI3K-AKT in human and murine leukemia cells, and activated phosphorylated p38 and phosphorylated ERK presented potent antiproliferative activity, which provided a potent small molecule for further cancer therapy.


Assuntos
Antineoplásicos , Leucemia , Neoplasias , Inibidores de Proteínas Quinases , Quinazolinonas , Animais , Humanos , Camundongos , Antineoplásicos/química , Proliferação de Células , Desenho de Fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Quinazolinonas/química , Quinazolinonas/farmacologia , Relação Estrutura-Atividade , Classe Ib de Fosfatidilinositol 3-Quinase
9.
Ecotoxicol Environ Saf ; 266: 115610, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37866036

RESUMO

Cadmium (Cd) exposure damages the reproductive system. Lipid droplets (LDs) play an important role in steroid-producing cells to provide raw material for steroid hormone. We have found that the LDs of Leydig cells exposed to Cd are bigger than those of normal cells, but the effects on steroidogenesis and its underlying mechanism remains unclear. Using Isobaric tag for relative and absolute quantitation (iTARQ) proteomics, phosphodiesterase beta-2 (PLCß2) was identified as the most significantly up-regulated protein in immature Leydig cells (ILCs) and adult Leydig cells (ALCs) derived from male rats exposed to maternal Cd. Consistent with high expression of PLCß2, the size of LDs was increased in Leydig cells exposed to Cd, accompanied by reduction in cholesterol and progesterone (P4) levels. However, the high PLCß2 did not result in high diacylglycerol (DAG) level, because Cd exposure up-regulated diacylglycerol kinases ε (DGKε) to promote the conversion from DAG to phosphatidic acid (PA). Exogenous PA, which was consistent with the intracellular PA concentration induced by Cd, facilitated the formation of large LDs in R2C cells, followed by reduced P4 level in the culture medium. When PLCß2 expression was knocked down, the increased DGKε caused by Cd was reversed, and then the PA level was decreased to normal. As results, large LDs returned to normal size, and the level of total cholesterol was improved to restore steroidogenesis. The accumulation of PA regulated by PLCß2-DAG-DGKε signal pathway is responsible for the formation of large LDs and insufficient steroid hormone synthesis in Leydig cells exposed to Cd. These data highlight that LD is an important target organelle for Cd-induced steroid hormone deficiency in males.


Assuntos
Cádmio , Células Intersticiais do Testículo , Ratos , Masculino , Animais , Células Intersticiais do Testículo/metabolismo , Cádmio/toxicidade , Cádmio/metabolismo , Gotículas Lipídicas/metabolismo , Fosfolipase C beta/metabolismo , Ácidos Fosfatídicos/metabolismo , Diglicerídeos/metabolismo , Transdução de Sinais , Esteroides/metabolismo , Progesterona/metabolismo , Colesterol/metabolismo
10.
BMC Surg ; 23(1): 172, 2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37355595

RESUMO

BACKGROUND: Distal radius fracture (DRF) is one of the most common orthopaedic-related traumas. DRF patients with die-punch fractures have a higher risk of loss of reduction, poorer functional outcomes, and increased risk of complications even after open reduction and internal fixation (ORIF). According to the three-column theory, the lunate fossa is an important part of the intermediate column for load bearing. When the distal radius fracture involves the lunate fossa, adequate anatomical reduction can have an important impact on the prognosis of wrist function. Herein, we used the combined volar and dorsal approach, and the dorsal approach was used to assist in bone grafting or dorsal plate fixation in reducing fractures. We compare the combined approach versus the Henry approach for the fixation of die-punch distal radius fractures. METHODS: We reviewed patients who were admitted for surgery for die-punch fractures from January 2016 to June 2021. The patients were followed-up after surgery to measure and evaluate their Gartland-Werley wrist score, wrist range of motion (ROM), and follow-up imaging data. RESULTS: There were 21 patients in the volar locking plate (VLP) group and 10 patients in the combined approach group. The majority of fractures in the VLP and combined approach groups were AO B and C fractures, respectively. The cause of injury and AO fracture classification showed significant differences between the two groups, and there was no difference in age or sex between the two groups. There was no significant difference in ROM between the two groups, but the VLP group presented a better Gartland-Werley score and volar tilt angle, and the combined group presented better maintenance in radial height and articular congruity. CONCLUSIONS: Reduction through the combined palmar and dorsal approach supplemented by bone grafting or dorsal plate fixation is an effective method for the treatment of die-punch distal radius fractures, which provides a new option for the treatment of die-punch fractures.


Assuntos
Fraturas do Rádio , Fraturas do Punho , Humanos , Placas Ósseas , Fixação Interna de Fraturas/métodos , Redução Aberta , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
11.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047111

RESUMO

Transcription factor (TF) families play important roles in plant stress responses. S. caninervis is a new model moss for plant desiccation tolerance studies. Here, we report a high-confidence identification and characterization of 591 TFs representing 52 families that covered all chromosomes in S. caninervis. GO term and KEGG pathway analysis showed that TFs were involved in the regulation of transcription, DNA-templated, gene expression, binding activities, plant hormone signal transduction, and circadian rhythm. A number of TF promoter regions have a mixture of various hormones-related cis-regulatory elements. AP2/ERF, bHLH, MYB, and C2H2-zinc finger TFs were the overrepresented TF families in S. caninervis, and the detailed classification of each family is performed based on structural features. Transcriptome analysis revealed the transcript abundances of some ScAP2/ERF, bHLH, MYB, and C2H2 genes were accumulated in the treated S. caninervis under cold, dehydration, and rehydration stresses. The RT-qPCR results strongly agreed with RNA-seq analysis, indicating these TFs might play a key role in S. caninervis response to abiotic stress. Our comparative TF characterization and classification provide the foundations for functional investigations of the dominant TF genes involved in S. caninervis stress response, as well as excellent stress tolerance gene resources for plant stress resistance breeding.


Assuntos
Bryopsida , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Estresse Fisiológico/genética , Bryopsida/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
12.
Molecules ; 28(12)2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37375135

RESUMO

Herein, we used isotopic formaldehyde and sodium cyanoborohydride via reductive amination to label two methyl groups on primary amine to arrange the standards (h2-formaldehyde-modified) and internal standards (ISs, d2-formaldehyde-modified) of tryptophan and its metabolites, such as serotonin (5-hydroxytryptamine) and 5-hydroxytryptophan. These derivatized reactions with a high yield are very satisfactory for manufacturing standards and ISs. This strategy will generate one or two methyl groups on amine to create different mass unit shifts with 14 vs. 16 or 28 vs. 32 in individual compounds for biomolecules with amine groups. In other words, multiples of two mass units shift are created using this derivatized method with isotopic formaldehyde. Serotonin, 5-hydroxytryptophan, and tryptophan were used as examples to demonstrate isotopic formaldehyde-generating standards and ISs. h2-formaldehyde-modified serotonin, 5-hydroxytryptophan, and tryptophan are standards to construct calibration curves, and d2-formaldehyde-modified analogs such as ISs spike into samples to normalize the signal of each detection. We utilized multiple reaction monitoring modes and triple quadrupole mass spectrometry to demonstrate the derivatized method suitable for these three nervous biomolecules. The derivatized method demonstrated a linearity range of the coefficient of determinations between 0.9938 to 0.9969. The limits of detection and quantification ranged from 1.39 to 15.36 ng/mL.


Assuntos
5-Hidroxitriptofano , Triptofano , 5-Hidroxitriptofano/metabolismo , Triptofano/metabolismo , Serotonina/metabolismo , Aminação , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Formaldeído/química , Cromatografia Líquida de Alta Pressão/métodos
13.
Anal Chem ; 94(30): 10737-10744, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35876030

RESUMO

Cysteine (Cys) plays an important role in many physiological activities of human beings. Various diseases are always accompanied by abnormal levels of Cys. A series of Cys-responsive probes were recently developed. However, most fluorescent probes have many disadvantages and exhibit poor in vivo imaging. Therefore, a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe with high selectivity and sensitivity (limit of detection = 10.6 nM) toward Cys was developed in this study. The new Probe I interacted with Cys to activate NIRF/PA signals, detecting Cys in vitro with a large emission wavelength (851 nm) and Stokes shift (191 nm), monitoring the occurrence of liver cancer in vivo. This work not only presented an effective NIRF/PA dual-mode dicyanoisophorone probe for the first time in the imaging of Cys but also provided a comprehensive and accurate tool for detecting different analytes and tumors in deeper tissues, which could be conducive to the early diagnosis of diseases.


Assuntos
Cisteína , Corantes Fluorescentes , Células HeLa , Humanos , Microscopia de Fluorescência/métodos , Imagem Óptica , Análise Espectral
14.
Ecotoxicol Environ Saf ; 232: 113255, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35121256

RESUMO

Cadmium (Cd) is one of the most common environmental pollutants, which has a long biological half-life. Maternal Cd-exposure in the natural environment causes steroidogenesis defects resulting in spermatogenesis disorder in male offspring. For better understanding its underlying mechanism, we have employed iTRAQ to screen the differentially expressed protein and found that the expression of CORO1A and Cofilin 1 was up-regulated approximately 2 fold in Leydig cells of maternal Cd-exposure offspring. As the major source of steroid hormone, cholesterol is transported to cells via receptor-mediated endocytosis which relies on the remodel of cytoskeleton, then stores in lipid droplets (LDs). However, few studies have focused on the role of cytoskeleton in abnormal steroidogenesis. This study was performed to explore the role of CORO1A in androgen deficiency caused by Cd exposure and its involvement of low-density lipoprotein (LDL) uptake and effects on LDs. We found that Cd resulted in the up-regulation of CORO1A and Cofilin 1, and down-regulation of Profilin 1 in the testis of male offspring with maternal exposure. The structure of filamentous actin was broken, disordered and even crumpled up in Cd-treated R2C cells. F-actin disassembly led to a low uptake of LDL with a reduced number of LDs, followed by decreased total cholesterol and low progesterone production. When CORO1A was silenced, the expression of Cofilin 1 was down-regulated and Profilin 1 was up-regulated in Cd-treated R2C cells. The filamentous actin was rescued and the integrated cytoskeleton prompted LDL uptake, which resulted in the increased total cholesterol and high progesterone production. These findings highlight the crucial role of CORO1A as a cytoskeleton regulatory protein in steroidogenesis, which may help to better understand Cd-induced steroid hormone deficiency in children.


Assuntos
Cádmio , Células Intersticiais do Testículo , Transporte Biológico , Cádmio/toxicidade , Feminino , Humanos , Lipoproteínas , Masculino , Exposição Materna
15.
Bioorg Chem ; 114: 105043, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34120019

RESUMO

Screening a natural product library of 850 compounds yield isoliquiritigenin as an effective anti-inflammatory agent by inhibiting the production of pro-inflammatory NO induced by Pam3CSK4, while its activity accompanied by toxicity. Further studies obtained the optimized isoliquiritigenin derivative SMU-B14, which can inhibit Pam3CSK4 triggered toll-like receptor 2 (TLR2) signaling with low toxicity and high potency. Preliminary mechanism studies indicated that SMU-B14 worked through TLR2/MyD88, phosphorylation of IKKα/ß, leading to the reduce degradation of NF-κB related IKBα and p65 complex, then inhibited the production of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß both in human and murine cell lines. Subsequent polarization experiments showed SMU-B14 significant reversed the polarization of M1 phenotype primary macrophage activated by Pam3CSK4in vitro, and reduced the infiltration of neutrophil and polarization of M1-type macrophage, decreased serum alanine transaminase (ALT), as a result protected liver from being injured in vivo. In summary, we obtained an optimized lead compound SMU-B14 and found it functionally blocked TLR2/MyD88/NF-κB signaling pathway to down-regulate the production of inflammatory cytokines resulted significant liver protection property.


Assuntos
Anti-Inflamatórios/uso terapêutico , Polaridade Celular/efeitos dos fármacos , Chalconas/uso terapêutico , Hepatite/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Doença Aguda , Animais , Anti-Inflamatórios/síntese química , Chalconas/síntese química , Citocinas/metabolismo , Hepatite/metabolismo , Hepatite/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Células THP-1
16.
Pak J Pharm Sci ; 34(3): 1003-1010, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602425

RESUMO

Rhizoma Musa (the Rhizome of Musa basjoo Sied.et Zucc.) is used as a traditional medical herb of Miao nationality in Guizhou province, in China. It has the efficacy of clearing heat and detoxifying, quenching thirst, diuresis, etc. Modern pharmacological studies have shown that it has hypoglycemic, inhibition of α-glucosidase, and anti-inflammatory activity. However, when the rhizomes of Musa basjoo are dug up, the rhizomes are unable regenerate, and the pseudostem and leaf are discarded, which not only pollutes the environment, but also causes a huge waste of herb resources. In this study, a UPLC-ELSD fingerprint analysis with chemometric method was applied for the evaluation of chemical similarity among rhizome, pseudostem and leaf of Musa Basjoo. The results indicated that the combined method could efficiently analyze and compare the chemical similarity among rhizome, pseudostem, and leaf of Musa Basjoo. The proposed method provides the foundation for the resource substitution of the rhizome, pseudostem, and leaf of Musa Basjoo.


Assuntos
Musa/química , Extratos Vegetais/química , Folhas de Planta/química , Rizoma/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Medicamentos de Ervas Chinesas , Difusão Dinâmica da Luz , Extratos Vegetais/análise , Caules de Planta/química , Análise de Componente Principal
17.
Mol Cancer ; 19(1): 15, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980023

RESUMO

Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis. In recent years, immunotherapy has also become an important focus of cancer research. Thus, to study the relationship between CTCs and immunotherapy is extremely necessary and valuable to improve the treatment of cancer. In this review, based on the advancements of CTC isolation technologies, we mainly discuss the clinical applications of CTCs in cancer immunotherapy and the related immune mechanisms of CTC formation. In order to fully understand CTC formation, sufficiently and completely understood molecular mechanism based on the different immune cells is critical. This understanding is a promising avenue for the development of effective immunotherapeutic strategies targeting CTCs.


Assuntos
Biomarcadores Tumorais/metabolismo , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Células Neoplásicas Circulantes/patologia , Animais , Humanos , Neoplasias/sangue , Neoplasias/metabolismo , Neoplasias/patologia , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/imunologia
18.
Org Biomol Chem ; 18(6): 1087-1090, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-31984412

RESUMO

A coupling of bromoalkynes with secondary phosphine oxides was developed for the synthesis of alkynylphosphine oxides. This transformation was accomplished under additive-free conditions in acetic anhydride (Ac2O). The reaction could be carried out under mild conditions, and a wide range of secondary phosphine oxides were obtained in good yields.

19.
Mol Divers ; 24(1): 21-30, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30796639

RESUMO

The dried rhizome of Musa basjoo Sieb. et Zucc. is Rhizoma Musae. It has been used to treat diabetes in Miao medicine in China. Lupenone was isolated from Rhizoma Musae and has good anti-diabetic activity. Its mechanism of action is unclear. Diabetes is a chronic low-level systemic inflammatory disease, and lupenone has anti-inflammatory activity, but the underlying mechanism is not fully elucidated. In this study, we aimed to construct the drug-target biologic network and predict the anti-inflammatory mechanism of lupenone. The network-based pharmacologic analysis platform was used to identify the target proteins related to inflammation. Furthermore, the effects of lupenone on acute, subacute and diabetic pancreatic inflammation were evaluated. The "component-target-disease" network was constructed using Cytoscape. Lupenone could regulate transcription factor p65, NF-kappa-B inhibitor alpha, transcription factor AP-1, NF-kappa-B essential modulator, nuclear factor NF-kappa-B p105 subunit, epidermal growth factor receptor, hypoxia-inducible factor 1-alpha and other proteins related to the PI3K-Akt, Toll-like receptor and NF-kappa B signaling pathways. In addition, lupenone significantly decreased acute and subacute inflammation in mice as well as the IL-1ß and IFN-γ levels in the pancreas of diabetic rats. The above results provide strong support for studying the molecular mechanism of lupenone in the treatment of diabetes from the perspective of anti-inflammation.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Biologia Computacional , Triterpenos/química , Triterpenos/farmacologia , Animais , Proteínas de Transporte , Biologia Computacional/métodos , Citocinas/metabolismo , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/etiologia , Mediadores da Inflamação , Masculino , Camundongos , Modelos Moleculares , Ligação Proteica , Ratos , Relação Estrutura-Atividade , Tecnologia Farmacêutica
20.
J Therm Biol ; 89: 102469, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32364963

RESUMO

We conducted laboratory experiments to determine the lethal temperatures of the shoots of dried Bryum argenteum and to determine how this restoration species responds to extreme environments. We specifically assessed changes in gene expression levels in the shoots of dried B. argenteum plants that were subjected to sudden heat shock (control (20 ± 2°C), 80°C, 100°C, 110°C or 120°C) followed by exposure to heat for an additional 10, 20, 30 or 60 min. After they were exposed to heat, the samples were placed in wet sand medium, and their survival and regeneration abilities were evaluated daily for 56 days. The results showed that lethal temperatures significantly reduced the shoot regeneration potential, delayed both shoot and protonemal emergence times and reduced the protonemal emergence area. In addition, the expression of nine genes (HSF3, HSP70, ERF, LEA, ELIP, LHCA, LHCB, Tr288 and DHN) was induced by temperature stress, as assessed after 30 min of exposure. Additionally, a new thermal tolerance level for dried B. argenteum - 120°C for 20 min - was determined, which was the highest temperature recorded for this moss; this tolerance exceeded the previous record of 110°C for 10 min. These findings help elucidate the survival mechanism of this species under heat shock stress and facilitate the recovery and restoration of destroyed ecosystems.


Assuntos
Briófitas/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Termotolerância , Briófitas/genética , Briófitas/metabolismo , Secas , Calor Extremo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Transcriptoma
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