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1.
Heliyon ; 10(12): e32773, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975129

RESUMO

B-box (BBX) proteins have been recognized as vital determinants in plant development, morphogenesis, and adaptive responses to a myriad of environmental stresses. These zinc-finger proteins play a pivotal role in various biological processes. Their influence spans photomorphogenesis, the regulation of flowering, and imparting resilience to a wide array of challenges, encompassing both biotic and abiotic factors. Chromosome localization, gene structure and conserved motifs, phylogenetic analysis, collinearity analysis, expression profiling, fluorescence quantitative analysis, and tobacco transient transformation methods were used for functional localization and expression pattern analysis of the DhBBX gene. A total of 23 DhBBX members were identified from Dendrobium huoshanense. Subsequent phylogenetic evaluations effectively segregated these genes into five discrete evolutionary subsets. The predictions of subcellular localizations revealed that all these proteins were localized in the nucleus. The genetic composition and patterns showed that the majority of these genes consisted of several exons, with a few variations that could be attributed to transposon insertion. A comprehensive analysis using qRT-PCR was conducted to unravel the expression patterns of these genes in D. huoshanense, with a specific concentration on their responses to various hormone treatments and cold stress. Subcellular localization reveals that DhBBX21 and DhBBX9 are located in the nucleus. Our results provide a deep comprehension of the complex regulatory mechanisms of BBXs in response to various environmental and hormonal stimuli. These discoveries encourage further detailed and focused investigations into the operational dynamics of the BBX gene family in a wider range of plant species.

2.
Anal Chem ; 96(24): 10084-10091, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38836421

RESUMO

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , DNA , MicroRNAs , Humanos , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/química , MicroRNAs/metabolismo , MicroRNAs/análise , DNA/química , DNA/metabolismo , Imagem Molecular/métodos , Animais , Imagem Óptica
3.
Front Genet ; 15: 1394790, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711915

RESUMO

Introduction: DNA-binding with one finger (Dof) transcription factors (TFs) are a unique family of TFs found in higher plants that regulate plant responses to light, hormones, and abiotic stresses. The specific involvement of Dof genes in the response to environmental stresses remains unknown in D. huoshanense. Methods: A total of 22 Dof family genes were identified from the D. huoshanense genome. Results: Chromosome location analysis showed that DhDof genes were distributed on 12 chromosomes, with the largest number of Dof genes located on chromosome 8. The phylogenetic tree revealed that DhDofs could be categorized into 11 distinct subgroups. In addition to the common groups, DhDof4, DhDof5, DhDof17, and the AtDof1.4 ortholog were clustered into the B3 subgroup. Group E was a newly identified branch, among which DhDof6, DhDof7, DhDof8, and DhDof9 were in an independent branch. The conserved motifs and gene structure revealed the differences in motif number and composition of DhDofs. The dof domain near the N-terminus was highly conserved and contained a C2-C2-type zinc finger structure linked with four cysteines. Microsynteny and interspecies collinearity revealed gene duplication events and phylogenetic tree among DhDofs. Large-scale gene duplication had not occurred among the DhDofs genes and only in one pair of genes on chromosome 13. Synteny blocks were found more often between D. huoshanense and its relatives and less often between Oryza sativa and Arabidopsis thaliana. Selection pressure analysis indicated that DhDof genes were subject to purifying selection. Expression profiles and correlation analyses revealed that the Dof gene under hormone treatments showed several different expression patterns. DhDof20 and DhDof21 had the highest expression levels and were co-expressed under MeJA induction. The cis-acting element analysis revealed that each DhDof had several regulatory elements involved in plant growth as well as abiotic stresses. qRT-PCR analysis demonstrated that DhDof2 was the main ABA-responsive gene and DhDof7 was the main cold stress-related gene. IAA suppressed the expression of some Dof candidates, and SA inhibited most of the candidate genes. Discussion: Our results may provide new insights for the further investigation of the Dof genes and the screening of the core stress-resistance genes.

4.
bioRxiv ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38798480

RESUMO

Lymphocytes can circulate as well as take residence within tissues. While the mechanisms by which circulating populations are recruited to infection sites have been extensively characterized, the molecular basis for the recirculation of tissue-resident cells is less understood. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network. Although the secondary lymphoid structure is an essential signal hub for adaptive lymphocyte differentiation and dispatch, it is redundant for ILC2 migration and effector function. Upon IL-25 stimulation, a dramatic change in epigenetic landscape occurs in intestinal ILC2s, leading to the expression of sphingosine-1-phosphate receptors (S1PRs). Among the various S1PRs, we found that S1PR5 is critical for ILC2 exit from intestinal tissue to lymph. By contrast, S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to distal tissues including the lung where the redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs for ILC2 migration is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. Thus, our study demonstrates a stage-specific requirement of different S1P receptors for ILC2 redistribution during infection. We therefore propose a fundamental paradigm that innate and adaptive lymphocytes utilize a shared vascular network frame and specialized navigation cues for migration.

5.
Physiol Mol Biol Plants ; 30(4): 527-542, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38737319

RESUMO

The TIFY family consists of plant-specific genes that regulates multiple plant functions, including developmental and defense responses. Here, we performed a comprehensive genomic analysis of TIFY genes in Dendrobium huoshanense. Our analysis encompassed their phylogenetic relationships, gene structures, chromosomal distributions, promoter regions, and patterns of collinearity. A total of 16 DhTIFY genes were identified, and classified into distinct clusters named JAZ, PPD, ZIM, and TIFY based on their phylogenetic relationship. These DhTIFYs exhibited an uneven distribution across 7 chromosomes. The expansion of the DhTIFY gene family appears to have been significantly influenced by whole-genome and segmental duplication events. The ratio of non-synonymous to synonymous substitutions (Ka/Ks) implies that the purifying selection has been predominant, maintaining a constrained functional diversification after duplication events. Gene structure analysis indicated that DhTIFYs exhibited significant structural variation, particularly in terms of gene organization and intron numbers. Moreover, numerous cis-acting elements related to hormone signaling, developmental processes, and stress responses were identified within the promoter regions. Subsequently, qRT-PCR experiments demonstrated that the expression of DhTIFYs is modulated in response to MeJA (Methyl jasmonate), cold, and drought treatment. Collectively, these results enhance our understanding of the functional dynamics of TIFY genes in D. huoshanense and may pinpoint potential candidates for detailed examination of the biological roles of TIFY genes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01442-9.

6.
Redox Biol ; 72: 103140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593629

RESUMO

Gut microbiota has been implicated in the initiation and progression of various diseases; however, the underlying mechanisms remain elusive and effective therapeutic strategies are scarce. In this study, we investigated the role and mechanisms of gut microbiota in TNBS-induced colitis and its associated kidney injury while evaluating the potential of dietary protein as a therapeutic intervention. The intrarectal administration of TNBS induced colitis in mice, concurrently with kidney damage. Interestingly, this effect was absent when TNBS was administered intraperitoneally, indicating a potential role of gut microbiota. Depletion of gut bacteria with antibiotics significantly attenuated the severity of TNBS-induced inflammation, oxidative damage, and tissue injury in the colon and kidneys. Mechanistic investigations using cultured colon epithelial cells and bone-marrow macrophages unveiled that TNBS induced cell oxidation, inflammation and injury, which was amplified by the bacterial component LPS and mitigated by thiol antioxidants. Importantly, in vivo administration of thiol-rich whey protein entirely prevented TNBS-induced colonic and kidney injury. Our findings suggest that gut bacteria significantly contribute to the initiation and progression of colitis and associated kidney injury, potentially through mechanisms involving LPS-induced exaggeration of oxidative cellular damage. Furthermore, our research highlights the potential of dietary thiol antioxidants as preventive and therapeutic interventions.


Assuntos
Colite , Microbioma Gastrointestinal , Estresse Oxidativo , Ácido Trinitrobenzenossulfônico , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Colite/induzido quimicamente , Colite/microbiologia , Colite/metabolismo , Camundongos , Ácido Trinitrobenzenossulfônico/toxicidade , Ácido Trinitrobenzenossulfônico/efeitos adversos , Modelos Animais de Doenças , Masculino , Antioxidantes/farmacologia , Rim/metabolismo , Rim/patologia , Rim/efeitos dos fármacos
7.
Int Urol Nephrol ; 56(7): 2431-2440, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38466510

RESUMO

BACKGROUND: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. METHODS: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. RESULTS: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. CONCLUSIONS: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.


Assuntos
Taxa de Filtração Glomerular , Humanos , Masculino , Idoso , Feminino , China , Idoso de 80 Anos ou mais , Cistatina C/sangue , Creatinina/sangue , Estudos Retrospectivos , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico
8.
Int J Biol Macromol ; 262(Pt 1): 129902, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307426

RESUMO

In situ imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific in situ imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HPAP) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific in situ imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HPAP was successfully constructed to trigger the cumulative amplification of fluorescence signal in situ. The specificity, sensitivity and serum stability of DTF-HPAP were verified in vitro, and DTF-HPAP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HPAP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias , Camundongos , Animais , MicroRNAs/genética , Endonucleases , Catálise , Técnicas Biossensoriais/métodos
9.
Nutrients ; 16(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38337722

RESUMO

Polygonum sibiricum, with its medicinal and edibility dual properties, has been widely recognized and utilized throughout Chinese history. As a kind of its effective component, Polygonum sibiricum polysaccharides (PSP) have been reported to be a promising novel antidepressant agent. Meanwhile, the precise mechanisms underlying its action remain elusive. The polarization state transition of microglia is intricately linked to neuroinflammation, indicating its crucial involvement in the pathophysiology of depression. Researchers are vigorously pursuing the exploration of this potential treatment strategy, aiming to comprehend its underlying mechanisms. Hence, the current study was designed to investigate the antidepressant mechanisms of PSP via Microglial M1/M2 Polarization, based on the lipopolysaccharide (LPS)-induced BV2 cell activation model. The results indicate that PSP significantly inhibited NO and LDH release and reduced ROS levels in LPS-induced BV2 cells. PSP could significantly reduce the protein expression level of Iba-1, decreased the mRNA levels of TNF-α, IL-1ß, and IL-6, and increased the mRNA level of IL-10. PSP also significantly reduced the protein expression level of CD16/32 and increased that of CD206, reduced the mRNA level and fluorescence intensity of iNOS, and increased those of Arg-1. However, PSP pretreatment reversed the alterations of the BDNF/TrkB/CREB and Notch/Hes1 pathways in LPS-induced BV2 cells. These results suggested that PSP exerted the anti-inflammatory effects by inhibiting M1 phenotype polarization and promoting microglia polarization toward the M2 phenotype, and its regulation of microglia M1/M2 polarization may be associated with modulating the BDNF/TrkB/CREB and Notch/Hes1 pathways.


Assuntos
Microglia , Polygonum , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Polygonum/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Antidepressivos/farmacologia , RNA Mensageiro/metabolismo
10.
BMC Genom Data ; 25(1): 22, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383301

RESUMO

OBJECTIVES: Pb stress has a negative impact on plant growth by interfering with photosynthesis and releasing reactive oxygen species, causing major risks such as heavy metal ion accumulation in the soil matrix. A proteomics experiment was conducted to determine whether protein levels of Dendrobium huoshanense changed in response to Pb stress seven to fifteen days after being sprayed with a 200 mg/L Pb (NO3)2 solution. The proteomic data we gathered provides a model for investigations into the mechanisms underlying Dendrobium plant resistance to heavy metal stress. DATA DESCRIPTION: A label-free quantitative proteomics approach was employed to examine the variations in protein expression levels of D. huoshanense at different times of Pb(NO3)2 treatment. We submitted the raw data obtained from these proteomics sequencing experiments to the ProteomeXchange database with the accession number PXD047050. 63,194 mass spectra in total were compared after being imported into the Proteome Discoverer software for database search. A total of 12,402 spectral peptides were identified with a confidence level exceeding 99%, which resulted in the identification of 2,449 significantly differential proteins. These proteins can be utilized for screening, functional annotation, and enrichment analysis of differentially expressed proteins before and after heavy metal treatment experiments.


Assuntos
Dendrobium , Metais Pesados , Dendrobium/metabolismo , Chumbo/metabolismo , Proteômica , Metais Pesados/metabolismo
11.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396684

RESUMO

Polysaccharides are one of the main active ingredients of Polygonum sibiricum (PS), which is a food and medicine homolog used throughout Chinese history. The antidepressant-like effects of PSP and its underlying mechanisms remain elusive, especially the regulation of microglial polarization. The current study determined the chemical composition and structural characteristics of PSP. Then, the chronic unpredictable mild stress (CUMS) procedure was carried out on the zebrafish for 5 weeks, and PSP was immersed for 9 days (1 h/d). The body weight of zebrafish was monitored, and behavioral tests, including the novel tank test and light and dark tank test, were performed to evaluate the antidepressant-like effects of PSP. Then, the function of the hypothalamic-pituitary-interrenal (HPI) axis, the levels of peripheral inflammation, neuronal and blood-brain barrier damage in the mesencephalon and telencephalon, and the mRNA expression of M1/M2 phenotype genes in the brain were examined. PSP samples had the typical structural characteristics of polysaccharides, consisting of glucose, mannose, and galactose, with an average Mw of 20.48 kDa, which presented porous and agglomerated morphologies. Compared with untreated zebrafish, the depression-like behaviors of CUMS-induced zebrafish were significantly attenuated. PSP significantly decreased the levels of cortisol and pro-inflammatory cytokines and increased the levels of the anti-inflammatory cytokines in the body of CUMS-induced depressive zebrafish. Furthermore, PSP remarkably reversed the neuronal and blood-brain barrier damage in the mesencephalon and telencephalon and the mRNA expression of M1/M2 phenotype genes in the brain. These findings indicated that the antidepressant-like effects of PSP were related to altering the HPI axis hyperactivation, suppressing peripheral inflammation, inhibiting neuroinflammation induced by microglia hyperactivation, and modulating microglial M1/M2 polarization. The current study provides the foundations for future examinations of PSP in the functional foods of emotional regulation.


Assuntos
Polygonum , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Microglia/metabolismo , Polygonum/metabolismo , Antidepressivos/farmacologia , Inflamação/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Citocinas/metabolismo , RNA Mensageiro/metabolismo , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
12.
ACS Omega ; 9(7): 7463-7470, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38405445

RESUMO

Papillary thyroid cancer (PTC) is generally treated as an indolent and curable cancer. However, the unavailability of surgery and ineffective radiotherapy persists in PTCs, resulting in poor outcomes and low survival rates. Thus, new chemotherapeutic strategies for PTCs are urgently needed. Resistance to ferroptosis remarkably contributes to cancer occurrence and progression. Artesunate (ART) has been repurposed as an anticancer drug, as it induces cell death in numerous cancers. However, whether ART induces ferroptosis in PTC cells and, consequently, facilitates PTC therapy remains elusive. Furthermore, overcoming the pharmacological limitations of ART is a key requirement to support its clinical application. Herein, we reanalyzed the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx) to characterize the occurrence of resistance to ferroptosis in thyroid cancer. In vitro results showed that ART induced ferroptosis in PTC cells by increasing the cellular iron content. The encapsulation of ART by liposomes did not alter the efficiency in inducing ferroptosis and inhibiting the invasion and migration of PTC cells compared with direct ART application. Thus, PTC resistance to ferroptosis can be overcome by ART and liposome-encapsulated ART.

13.
Front Immunol ; 15: 1309509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352877

RESUMO

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.


Assuntos
Neoplasias do Colo , Nanopartículas , Piperazinas , Piridinas , Humanos , Interleucina-2/farmacologia , Interleucina-2/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Imunidade
14.
Int J Biol Macromol ; 261(Pt 2): 129874, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307430

RESUMO

Bletilla Striata (BS) Polysaccharide (BSP) is one of the main components of the traditional Chinese medicinal plant Bletilla striata Rchb. F. BSP has been widely used in antimicrobial and hemostasis treatments in clinics. Despite its use in skin disease treatment and cosmetology, the effects of BSP on wound healing remain unclear. Here we investigated the anti-inflammatory, antioxidant, and analgesic effects of BSP and explored its impact on morphological changes and inflammatory mediators during wound healing. A carrageenan-induced mouse paw edema model was established to evaluate the anti-inflammatory effect of BSP. Antioxidant indicators, including NO, SOD, and MDA, were measured in the blood and liver. The increased pain threshold induced by BSP was also determined using the hot plate test. A mouse excisional wound model was applied to evaluate the wound healing rate, and HE staining and Masson staining were used to detect tissue structure changes. In addition, ELISA was employed to detect the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß in serum. BSP significantly decreased the concentration of NO and MDA in serum and liver while increasing SOD activity. It exhibited a notable improvement in mouse paw edema induced by carrageenan. BSP dose-dependently delayed the appearance of licking behavior in mice, indicating its analgesic effect. Compared to the control group, the wound healing rate was significantly improved in the BSP treatment group. HE and Masson staining results showed that the BSP and 'Jingwanhong' ointment groups had slightly milder inflammatory responses and significantly promoted more new granulation tissue formation. The levels of serum inflammatory mediators TNF-α, IL-1ß, and IL-6 were reduced to varying degrees. The results demonstrated that BSP possesses anti-inflammatory, antioxidant, analgesic, and wound healing properties, and it may promote wound healing through inhibition of inflammatory cytokine synthesis and release.


Assuntos
Antioxidantes , Fator de Necrose Tumoral alfa , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carragenina/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Interleucina-6 , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Citocinas/metabolismo , Superóxido Dismutase/farmacologia , Cicatrização , Edema/induzido quimicamente , Edema/tratamento farmacológico , Mediadores da Inflamação/farmacologia
15.
Molecules ; 29(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257396

RESUMO

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a-4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with an IC50 value of 27.57 ± 0.52 µM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.


Assuntos
Apoptose , Desoxiadenosinas , Desoxiadenosinas/farmacologia , Western Blotting , Ciclo Celular
16.
Int J Biol Macromol ; 255: 128218, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992933

RESUMO

Peucedanum praeruptorum Dunn, a traditional Chinese medicine rich in coumarin, belongs to the Apiaceae family. A high-quality assembled genome of P. praeruptorum is lacking, which has posed obstacles to functional identification and molecular evolution studies of genes associated with coumarin production. Here, a chromosome-scale reference genome of P. praeruptorum, an important medicinal and aromatic plant, was first sequenced and assembled using Oxford Nanopore Technologies and Hi-C sequencing. The final assembled genome size was 1.83 Gb, with a contig N50 of 11.12 Mb. The entire BUSCO evaluation and second-generation read comparability rates were 96.0 % and 99.31 %, respectively. Furthermore, 99.91 % of the genome was anchored to 11 pseudochromosomes. The comparative genomic study revealed the presence of 18,593 orthogroups, which included 476 species-specific orthogroups and 1211 expanded gene families. Two whole-genome duplication (WGD) events and one whole-genome triplication (WGT) event occurred in P. praeruptorum. In addition to the γ-WGT shared by core eudicots or most eudicots, the first WGD was shared by Apiales, while the most recent WGD was unique to Apiaceae. Our study demonstrated that WGD events that occurred in Apioideae highlighted the important role of tandem duplication in the biosynthesis of coumarins and terpenes in P. praeruptorum. Additionally, the expansion of the cytochrome P450 monooxygenase, O-methyltransferase, ATP-binding cassette (ABC) transporter, and terpene synthase families may be associated with the abundance of coumarins and terpenoids. Moreover, we identified >170 UDP-glucosyltransferase members that may be involved in the glycosylation post-modification of coumarins. Significant gene expansion was observed in the ABCG, ABCB, and ABCC subgroups of the ABC transporter family, potentially facilitating the transmembrane transport of coumarins after bolting. The P. praeruptorum genome provides valuable insights into the machinery of coumarin biosynthesis and enhances our understanding of Apiaceae evolution.


Assuntos
Apiaceae , Cumarínicos , Cumarínicos/química , Sistema Enzimático do Citocromo P-450/genética , Apiaceae/genética , Apiaceae/química , Metiltransferases/genética , Cromossomos
17.
Small ; 20(16): e2306989, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38032164

RESUMO

Hybrid organic-inorganic perovskite (HOIP) ferroelectric materials have great potential for developing self-powered electronic transducers owing to their impressive piezoelectric performance, structural tunability and low processing temperatures. Nevertheless, their inherent brittle and low elastic moduli limit their application in electromechanical conversion. Integration of HOIP ferroelectrics and soft polymers is a promising solution. In this work, a hybrid organic-inorganic rare-earth double perovskite ferroelectric, [RM3HQ]2RbPr(NO3)6 (RM3HQ = (R)-N-methyl-3-hydroxylquinuclidinium) is presented, which possesses multiaxial nature, ferroelasticity and satisfactory piezoelectric properties, including piezoelectric charge coefficient (d33) of 102.3 pC N-1 and piezoelectric voltage coefficient (g33) of 680 × 10-3 V m N-1. The piezoelectric generators (PEG) based on composite films of [RM3HQ]2RbPr(NO3)6@polyurethane (PU) can generate an open-circuit voltage (Voc) of 30 V and short-circuit current (Isc) of 18 µA, representing one of the state-of-the-art PEGs to date. This work has promoted the exploration of new HOIP ferroelectrics and their development of applications in electromechanical conversion devices.

18.
ACS Nano ; 18(1): 770-782, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38113242

RESUMO

Interleukin-2 (IL-2) used in multiple sclerosis (MS) therapy modulates the balance between regulatory T (Treg) cells and effector T (Teff) cells. However, the off-target activation of Teff cells by IL-2 limits its clinical application. Therefore, a rapidly prepared immunoswitch nanomodulator termed aT-IL2C NPs was developed, which specifically recognized Treg cells with high TIGIT expression thanks to the presence of an anti-TIGIT and an IL-2/JES6-1 complex (IL2C) being delivered to Treg cells but not to Teff cells with low TIGIT expression. Then, IL2C released IL-2 due to the specific expression of the high-affinity IL-2 receptor on Treg cells, thus enabling the active targeting and selective proliferation of Treg cells. Moreover, the anti-TIGIT of aT-IL2C NPs selectively inhibited the proliferation of Teff cells while leaving the proliferation of Treg cells unaffected. In addition, since the IL-2 receptor on Teff cells had medium-affinity, the IL2C hardly released IL-2 to Teff cells, thus enabling the inhibition of Teff cell proliferation. The treatment of experimental autoimmune encephalomyelitis (EAE) mice with aT-IL2C NPs ameliorated the severity of the EAE and restored white matter integrity. Collectively, this work described a potential promising agent for effective MS therapy.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Linfócitos T Reguladores , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Interleucina-2/farmacologia , Interleucina-2/uso terapêutico , Interleucina-2/metabolismo , Encefalomielite Autoimune Experimental/tratamento farmacológico , Proliferação de Células , Camundongos Endogâmicos C57BL
20.
Dalton Trans ; 52(44): 16406-16412, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37870776

RESUMO

Organic-inorganic hybrid perovskites (OIHPs) with dielectric switching functions have aroused comprehensive scientific interest, benefitting from their promising applications in sensors and information storage. However, to date, most of these materials discovered thus far possess a single function and are limited in their applicability, failing to meet the requirements of diverse applications. Moreover, the discovery of these materials has been largely serendipitous. Building multifunctional OIHPs with dielectric switching and semiconductors remains a daunting task. In this context, by introducing [C7H16N]+ as cations and in combination with lead halide with semiconducting properties, two OIHPs [C7H16N]PbI3 (1) and [C7H16N]PbBr3 (2) ([C7H16N]+ = (cyclopropylmethyl) trimethylammonium) have been successfully designed. They have dielectric switching properties close to 253 and 279 K and semiconducting behavior with band gaps of 2.67 and 3.22 eV. The phase transition temperature increased by 26 K through halogen substitution. In summary, our findings in this study provide insights into the application of the halogen substitution regulation strategy and open up new possibilities for designing perovskite semiconductors with dielectric switching functionality.

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