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1.
Jpn J Clin Oncol ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415305

RESUMO

The outbreak of the coronavirus disease (COVID-19) occurred in Wuhan, China, in December 2019. As of 21 March 2020, this epidemic has spread to 179 countries with more than 200 000 confirmed cases and 8578 deaths. The outbreak has put enormous pressure on the medical establishment and even led to exhaustion of medical resources in the most affected areas. Other medical work has been significantly affected in the context of COVID-19 epidemic. In order to reduce or avoid cross-infection with COVID-19, many hospitals have taken measures to limit the number of outpatient visits and inpatients. For example, emergency surgery can only be guaranteed, and most other surgeries can be postponed. Patients with cancer are one of the groups most affected by the epidemic because of their systematic immunosuppressive state and requirement of frequent admission to hospital. Consequently, specific adjustments for their treatment need to be made to cope with this situation. Therefore, it is of significance to summarize the relevant experience of China in the prevention and control of COVID-19 infection and treatment of patients with cancer during the epidemic.

3.
Biomater Sci ; 8(9): 2472-2480, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32196028

RESUMO

Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune regulation in the tumor microenvironments. To enhance the antitumor activity, we developed injectable pH-degradable PVA microgels encapsulated with oncolytic adenovirus (OA) by microfluidics for localized OA delivery and cancer treatments. PVA microgels were tailored with an OA encapsulation efficiency of 68% and exhibited a pH-dependent OA release as the microgel degradation at mildly acidic conditions. PVA microgels mediated fast viral release and increased replication in HEK293T and A549 cells at a lower pH, and the replication efficiency could be further reinforced by co-loading with one BET bromodomain inhibitor JQ1, inducing significant cytotoxicity against A549 cells. An in vivo study revealed that OA release was highly located at the tumor tissue assisted by PVA microgels, and the OA infection was also enhanced with the addition of JQ1 treatment, meanwhile greatly inhibiting the PD-L1 expression to overcome the immune suppression. OA/JQ1 co-encapsulated injectable microgels exhibited a superior in vivo antitumor activity on the A549 lung tumor-bearing mice by the combination of inhibited proliferation, amplified oncolysis, and potential immune regulation.

4.
Research (Wash D C) ; 2020: 4825185, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110778

RESUMO

Most of the existing acoustic metamaterials rely on architected structures with fixed configurations, and thus, their properties cannot be modulated once the structures are fabricated. Emerging active acoustic metamaterials highlight a promising opportunity to on-demand switch property states; however, they typically require tethered loads, such as mechanical compression or pneumatic actuation. Using untethered physical stimuli to actively switch property states of acoustic metamaterials remains largely unexplored. Here, inspired by the sharkskin denticles, we present a class of active acoustic metamaterials whose configurations can be on-demand switched via untethered magnetic fields, thus enabling active switching of acoustic transmission, wave guiding, logic operation, and reciprocity. The key mechanism relies on magnetically deformable Mie resonator pillar (MRP) arrays that can be tuned between vertical and bent states corresponding to the acoustic forbidding and conducting, respectively. The MRPs are made of a magnetoactive elastomer and feature wavy air channels to enable an artificial Mie resonance within a designed frequency regime. The Mie resonance induces an acoustic bandgap, which is closed when pillars are selectively bent by a sufficiently large magnetic field. These magnetoactive MRPs are further harnessed to design stimuli-controlled reconfigurable acoustic switches, logic gates, and diodes. Capable of creating the first generation of untethered-stimuli-induced active acoustic metadevices, the present paradigm may find broad engineering applications, ranging from noise control and audio modulation to sonic camouflage.

5.
J Colloid Interface Sci ; 567: 145-153, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32045736

RESUMO

In this work, flower-like Bi2MoO6 nanoparticles grown on FTO substrates were firstly fabricated using a seed-free hydrothermal method. The Bi2MoO6 nanoflowers exhibited, to the best of our knowledge, higher photoelectrochemical (PEC) performances than other previously reported morphologies. It is generally accepted that the formation of type-I heterostructures is unfavorable for PEC applications. Nevertheless, in this work, we have successfully constructed a novel type-I architecture with numerous electron transport channels. In this unique Bi2MoO6/BiVO4 structure, BiVO4 films were continuously distributed on both the surfaces and the interstices of Bi2MoO6 nanoflowers. Interconnected BiVO4 nanoparticles could intimately contact with FTO substrates and thus constitute the electron transport channels, which could promptly transfer electrons to FTO substrates. Simultaneously, a cocatalyst of g-C3N4 was modified on the surfaces of BiVO4 to capture the photogenerated holes. As a result, the PEC activities of Bi2MoO6/BiVO4 heterostructures were significantly improved due to the enhanced charge carriers separation efficiency. The special design of electron transport channel may provide a universal strategy to address the intrinsic drawbacks of type-I heterostructures.

6.
Circulation ; 141(19): 1554-1569, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32098494

RESUMO

BACKGROUND: In mammals, regenerative therapy after myocardial infarction is hampered by the limited regenerative capacity of adult heart, whereas a transient regenerative capacity is maintained in the neonatal heart. Systemic phosphorylation signaling analysis on ischemic neonatal myocardium might be helpful to identify key pathways involved in heart regeneration. Our aim was to define the kinase-substrate network in ischemic neonatal myocardium and to identify key pathways involved in heart regeneration after ischemic insult. METHODS: Quantitative phosphoproteomics profiling was performed on infarct border zone of neonatal myocardium, and kinase-substrate network analysis revealed 11 kinases with enriched substrates and upregulated phosphorylation levels, including checkpoint kinase 1 (CHK1) kinase. The effect of CHK1 on cardiac regeneration was tested on Institute of Cancer Research CD1 neonatal and adult mice that underwent apical resection or myocardial infarction. RESULTS: In vitro, CHK1 overexpression promoted whereas CHK1 knockdown blunted cardiomyocyte proliferation. In vivo, inhibition of CHK1 hindered myocardial regeneration on resection border zone in neonatal mice. In adult myocardial infarction mice, CHK1 overexpression on infarct border zone upregulated mammalian target of rapamycin C1/ribosomal protein S6 kinase b-1 pathway, promoted cardiomyocyte proliferation, and improved cardiac function. Inhibiting mammalian target of rapamycin activity by rapamycin blunted the neonatal cardiomyocyte proliferation induced by CHK1 overexpression in vitro. CONCLUSIONS: Our study indicates that phosphoproteome of neonatal regenerative myocardium could help identify important signaling pathways involved in myocardial regeneration. CHK1 is found to be a key signaling responsible for neonatal regeneration. Myocardial overexpression of CHK1 could improve cardiac regeneration in adult hearts by activating the mammalian target of rapamycin C1/ribosomal protein S6 kinase b-1 pathway. Thus, CHK1 might serve as a potential novel target in myocardial repair after myocardial infarction.

7.
Cancer Med ; 9(8): 2621-2630, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32064794

RESUMO

BACKGROUND: Anlotinib showed significant survival benefits in advanced non-small cell lung cancer (NSCLC) patients as a third- or further-line treatment in the ALTER0303 trial. We aimed to evaluate the efficacy of anlotinib in patients with different histologies. METHODS: The ALTER0303 trial was a randomized, open-label, phase 3 study of anlotinib in NSCLC patients previously treated with at least two lines of chemotherapy or a tyrosine kinase inhibitor (TKI) in 31 centers in China. Patients were randomly assigned at a 2:1 ratio to receive anlotinib (12 mg QD from days 1 to 14 of a 21-day cycle) or placebo until progression or intolerable toxicity. The primary endpoint was overall survival (OS). We assessed the efficacy of anlotinib in histological subgroups in the full analysis set. RESULTS: In the ALTER0303 trial, 336 patients had the histological subtype of adenocarcinoma (ACC), 86 patients had the histological subtype of squamous cell carcinoma (SCC), and 15 patients had another subtype. In the ACC subgroup, the median OS time was significantly improved with anlotinib compared with placebo (9.6 months vs 6.9 months, P = .0051), as was the median progression-free survival (PFS) time (5.5 months vs 1.4 months, P < .0001). In the SCC subgroup, the median OS time was 10.7 months in the anlotinib group and 6.5 months in the placebo group (P = .2570), and the median PFS time was 4.8 months and 2.7 months (P = .0004), respectively. The common adverse events observed in the SCC and ACC subgroups were similar. CONCLUSIONS: Our findings suggest that anlotinib significantly improves PFS and OS in ACC patients and has a tendency to prolong survival in SCC patients.

8.
Biochem Biophys Res Commun ; 521(3): 814-820, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31708099

RESUMO

The dysregulation of Long noncoding RNAs (lncRNAs) has been implicated in many cardiovascular diseases, including cardiac fibrosis. However, the functions and mechanisms of lncRNAs in cardiac fibroblasts (CFs) have not been fully elucidated. First, we observed a correlation between cardiac remodeling (CR) and lncRNA FAF (FGF9-associated factor, termed FAF) expression in the heart. In vitro, we found that the expression of lncRNA FAF was altered in CFs, whereas it behaved inconsistently in cardiomyocytes (CMs). Next, we investigated the effects of lncRNA FAF on angiotensinogen II (Ang II)-induced cardiac fibrosis in neonatal rat CFs and explored the mechanism underlying these effects. In this study, lncRNA FAF was enriched in CFs and was associated with cardiac fibrosis. Upregulation of lncRNA FAF significantly restrained Ang II-induced increases in cell proliferation, differentiation and collagen accumulation of CFs. Moreover, we found that the function of lncRNA FAF was mainly realized through Transforming growth factor ß1 (TGFß1) secretion and then downregulated phosphorylation of Smad2/3. Additional analysis revealed that Fibroblast growth factor 9 (FGF9) is a direct target of lncRNA FAF, as the overexpression of lncRNA FAF could increase the expression of FGF9 and knockdown of the FGF9 expression could attenuate the down-regulation of lncRNA FAF on TGFß1-P-Smad2/3 pathway. Furthermore, knockdown of the FGF9 expression also abolished the inhibitory effect of FAF on fibrosis. In summary, we demonstrated that the overexpression of lncRNA FAF could inhibit fibrosis induced by Ang II via the TGFß1-P-Smad2/3 signalling by targeting FGF9 in CFs.

9.
Biomed Pharmacother ; 121: 109595, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31710896

RESUMO

Pyroptosis is an inflammatory form of cell death triggered by certain inflammasomes, leading to the cleavage of gasdermin D (GSDMD) and activation of inactive cytokines like IL-18 and IL-1ß. Pyroptosis has been reported to be closely associated to some diseases like atherosclerosis and diabetic nephropathy. Recently, some studies found that pyroptosis can influence the proliferation, invasion and metastasis of tumor, which regulated by some non-coding RNAs and other molecules. Hence, we provided an overview of morphological and molecular characteristics of pyroptosis. We also focus on mechanism of regulating pyroptosis in tumor cells as well as the potential roles of pyroptosis in cancer to explore potential diagnostic markers in cancers contributing to the prevention and treatment in cancers.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117937, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31865099

RESUMO

Polyphenols have been known to have significant binding affinity for proteins, and the specific condition (such as pH) could affect the degree of binding, the formation of covalent bond, and non-covalent interaction. In this study, characteristics of binding quercetin (Q) to wheat gliadin (G) which is a strong food allergen, were studied from pH 2.0 to pH 9.0. The results showed that Q quenched the fluorescence intensity of G by dynamic and static quenching modes and the stoichiometry of binding was close to 1. Intermolecular binding distances were smaller than 8 nm. Thermodynamic parameters suggested that hydrophobic force took charge of the formation of complexes at pH 2.0-4.0, whereas hydrogen bonds and van der Waals forces at pH 5.0-9.0. Analyses of the Fourier transform infrared and the Raman spectra along with synchronous fluorescence spectra revealed secondary and tertiary structural alterations and microenvironmental changed around protein fluorophores upon complexation with Q. The gauche-gauche-trans conformation increased at the expenses of the gauche-gauche-gauche conformation and the transition from ß-turn and random coil to α-helix and ß-sheet at pH 5.0 might decrease the allergenicity of G. These results provided new insights into G/Q interactions at different pH values, which may have potentials in decreasing allergen immunoreactivity.

11.
Biomark Res ; 7: 27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31832192

RESUMO

EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have achieved remarkable outcomes in the treatment of patients with EGFR-mutant non-small-cell lung cancer, but acquired resistance is still the main factor restricting their long-term use. In addition to the T790 M mutation of EGFR, amplification of the MET (or c-MET) gene has long been recognized as an important resistance mechanism for first- or second-generation EGFR-TKIs. Recent studies suggest that a key mechanism of acquired resistance to third-generation EGFR-TKIs (such as osimertinib) may be MET amplification and/or protein overactivation, especially when they are used as a first-line treatment. Therefore, in patients resistant to first-generation EGFR-TKIs caused by MET amplification and/or protein overactivation, the combination of osimertinib with MET or MEK inhibitors may be considered.

12.
Hepatology ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31758709

RESUMO

Major vault protein (MVP) is up regulated during infections with hepatitis B and C virus. Here, we found that MVP deficiency inhibited hepatocellular carcinoma (HCC) development induced by di-ethyl-nitrosamine (DEN), HBx, and HCV Core. Forced MVP expression was sufficient to induce HCC in mice. Mechanistic studies demonstrate that the ubiquitin ligase Human Double Minute 2 (HDM2) forms mutual exclusive complexes either with interferon regulatory factor 2 (IRF2) or with p53. In presence of MVP, HDM2 is liberated from IRF2 leading to the ubiquitination of the tumor suppressor p53. Mouse xenograft models showed that Hepatitis B and C virus promote carcinogenesis through MVP induction, resulting in a loss of p53 mediated by HDM2. Analyses of clinical samples from chronic hepatitis B, liver cirrhosis, and HCC revealed that MVP upregulation correlates with several hallmarks of malignancy, and associates with poor overall survival. Taken together, through the sequestration of IRF2, MVP promotes an HDM2-dependent loss of p53 that promotes HCC development.

13.
Transl Lung Cancer Res ; 8(5): 575-583, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31737494

RESUMO

Background: Lung cancer remains one of the deadliest cancers worldwide. The ALTER0303 trial revealed that anlotinib might be used as a third-line or further treatment in non-small cell lung cancer (NSCLC) patients. Meanwhile, the impact of previous therapy strategies on the efficiency of anlotinib still remains unknown. Methods: The subgroup of patients in ALTER0303 were analyzed by using Kaplan-Meier estimates, Pearson χ2, or Fisher's exact test. Results: There was no statistical significance on progression-free survival (PFS) and overall survival (OS) among patients in different previous antiangiogenic treatments groups. Patients in the chest radiotherapy (CRT) group had longer median PFS than the non-CRT group (5.93 vs. 4.63 m, P=0.027). Regardless of what kind of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) and chemotherapy regimens were used previously, all patients gained longer PFS in the anlotinib group, while only patients treated with vinorelbine/platinum in the EGFR wild type group, pemetrexed/platinum, vinorelbine/platinum, and gefitinib in the EGFR mutation group, and EGFR TKI used as the first line group could benefit from anlotinib on OS. When the OS was calculated from the time of diagnosis to the death, anlotinib could have increased median OS about 6 months (33.8 vs. 27.8 m, P<0.001) compared to the placebo with a hazard ratio (HR) (95% CI): 0.77 (0.60, 1.00). Conclusions: This study indicated that previous bevacizumab or endostatin treatments had no impact on the efficiency of anlotinib. Patients with CRT history benefited more from anlotinib on PFS. EGFR TKI and chemotherapy treatment history had more impact on OS than PFS in patients treated with anlotinib compared to placebo.

14.
Front Oncol ; 9: 1117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31709184

RESUMO

Esophageal squamous cell carcinoma (ESCC), which is characterized by invasiveness and poor prognosis, is the sixth most common leading cause of cancer-related death worldwide. Despite advances in multimodality therapy, ESCC mortality remains high, and an understanding of the molecular changes that lead to ESCC development and progression remains limited. In the present study, Integrin Binding Sialoprotein (IBSP) upregulation was found in 182 of 269 (67.7%) primary ESCC cells at the mRNA level by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, IHC staining further demonstrated that IBSP was upregulated in ESCC patients and IBSP protein upregulation was significantly related to the lymph node metastasis (P = 0.017), clinicopathologic stage (P = 0.001) and poor disease survival (P = 0.002). Moreover, functional studies illustrated that the IBSP gene can promote the proliferation and metastasis of ESCC cells. Furthermore, IBSP was found to regulate epithelial-mesenchymal transition (EMT), which promotes tumor cell metastasis. In conclusion, our study suggests that IBSP may be a valuable prognostic marker for ESCC patients.

15.
Adv Sci (Weinh) ; 6(19): 1900721, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31592412

RESUMO

Anlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non-small cell lung cancer (NSCLC) patients is still elusive. Here, tumor-specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. For patients with no durable benefit and durable clinical benefit patients, three predictors: germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB), and unfavorable mutation score of circulating DNA profiling are identified. Through integrating the advantages and disadvantages of three independent predictors, the tumor mutation index (TMI) is established as a prediction model and the patients who are very likely to benefit more from anlotinib therapy are identified. Furthermore, the IDH1 exon 4 mutation is identified as an unfavorable factor for anlotinib therapy under TMI-based stratification, and the TMI plus IDH1 exon 4 mutation status potentially predicts response to anlotinib. Collectively, this study provides a circulating DNA sequencing-based stratification method for identifying anlotinib responders via a noninvasive approach, and thus potentially improves the clinical outcome of NSCLC patients receiving third-line therapy.

16.
Int J Cancer ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618441

RESUMO

The endosome is a membrane-bound organ inside most eukaryotic cells, playing an important role in adaptive immunity by delivering endocytosed antigens to both MHC class I and II pathways. Here, by analyzing genotyping data from two published genome-wide association studies (GWASs), we evaluated associations between genetic variants in the endosome-related gene-set and survival of patients with nonsmall cell lung cancer (NSCLC). The discovery included 44,112 (3,478 genotyped and 40,634 imputed) single-nucleotide polymorphisms (SNPs) in 220 genes in a singlelocus analysis for their associations with survival of 1,185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. After validation of the 821 survival-associated significant SNPs in additional 984 NSCLC patients from the Harvard Lung Cancer Susceptibility Study, 14 SNPs remained significant. The final multivariate stepwise Cox proportional hazards regression modeling of the PLCO dataset identified three potentially functional and independent SNPs (i.e., KIF16B rs1555195 C>T, NEDD4L rs11660748 A>G and rs73440898 A>G) with an adjusted hazards ratio (HR) of 0.86 (95% confidence interval [CI] = 0.79-0.94, p = 0.0007), 1.31 (1.16-1.47, p = 6.0 × 10-5 ) and 1.27 (1.12-1.44, p = 0.0001) for overall survival (OS), respectively. Combined analysis of the adverse genotypes of these three SNPs revealed a trend in the genotype-survival association (ptrend < 0.0001 for OS and ptrend < 0.0001 for disease-specific survival). Furthermore, the survival-associated KIF16B rs1555195T allele was significantly associated with decreased mRNA expression levels of KIF16B in both lung tissues and blood cells. Therefore, genetic variants of the endosome-related genes may be biomarker for NSCLC survival, possibly through modulating the expression of corresponding genes.

17.
Acta Pharm Sin B ; 9(5): 902-922, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31649842

RESUMO

In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.

18.
Curr Microbiol ; 76(12): 1537-1544, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31555854

RESUMO

One novel ascomycetous yeast strain TF5-16-2 was isolated from water samples of Tuofengling crater lake located in Da Hinggan Ling Mountain, in the Inner Mongolia province of China. Morphological, physiological characteristics, as well as phylogenetic analyses of D1/D2 domains of the large subunit rRNA (LSU), ITS region, small subunit rRNA (SSU), and elongation factor-1α (EF-1α) were performed and finally confirmed the phylogenetic placement of strain TF5-16-2 in the genus Wickerhamomyces. Sequences analysis revealed that strain TF5-16-2 differed from its most closely related phylogenetic neighbors 'Candida' silvicultrix CBS 6269T and Wickerhamomyces anomalus CBS 5759T by 8.0% (including 2.3% gaps), 8.5% (including 2.4% gaps) divergences in D1/D2 domains of LSU, and 11% (including 4.3% gaps) and 13% (including 4.4% gaps) divergences in ITS region, respectively. As the considerable sequence divergence and distinguishable physiological characteristics, strain TF5-16-2 was proposed as a new species of the genus Wickerhamomyces, with the name Wickerhamomyces kurtzmanii sp. nov. (holotype = CGMCC 2.5597, Mycobank number is MB829959).


Assuntos
Lagos/microbiologia , Saccharomycetales/isolamento & purificação , China , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Proteínas Fúngicas/genética , Técnicas de Tipagem Micológica , Fator 1 de Elongação de Peptídeos/genética , Filogenia , Saccharomycetales/classificação , Saccharomycetales/genética
19.
Plant Physiol ; 181(3): 1223-1238, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31515447

RESUMO

In flowering plants, the tapetum cells in anthers undergo programmed cell death (PCD) at the late meiotic stage, providing nutrients for further development of microspores, including the formation of the pollen wall. However, the molecular basis of tapetum PCD remains elusive. Here we report a tapetum PCD-related mutant in rice (Oryza sativa), earlier degraded tapetum 1 (edt1), that shows complete pollen abortion associated with earlier-than-programmed tapetum cell death. EDT1 encodes a subunit of ATP-citrate lyase (ACL), and is specifically expressed in the tapetum of anthers. EDT1 localized in both the nucleus and the cytoplasm as observed in rice protoplast transient assays. We demonstrated that the A and B subunits of ACL interacted with each other and might function as a heteromultimer in the cytoplasm. EDT1 catalyzes the critical steps in cytosolic acetyl-CoA synthesis. Our data indicated a decrease in ATP level, energy charge, and fatty acid content in mutant edt1 anthers. In addition, the genes encoding secretory proteases or lipid transporters, and the transcription factors known to regulate PCD, were downregulated. Our results demonstrate that the timing of tapetum PCD must be tightly regulated for successful pollen development, and that EDT1 is involved in the tapetum PCD process. This study furthers our understanding of the molecular basis of pollen fertility and fecundity in rice and may also be relevant to other flowering plants.

20.
Front Pharmacol ; 10: 925, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507421

RESUMO

Insomnia is a common and widespread sleeping disorder caused by various risk factors. Though beneficial, conventional treatments of insomnia have significant limitations. As an alternative treatment, Chinese herbal formula Suanzaoren prescription (SZRP), composed of Suanzaoren [seeds of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow] and four additional herbs, has been reported with significant anti-insomnia effects. Yet the anti-insomnia mechanism of the herb formulae remains unknown. In this study, we attempted to extrapolate the holistic anti-insomnia mechanism of SZRP through herbal targeting and network pharmacology. The results indicated that the ingredients of Suanzaoren can target multi-neurotransmitter receptors at synapse interface, which was reported to be associated with sedative and hypnotic effects, while the four additional herbs can hit multiple pathways downstream of membrane neurotransmitters. Furthermore, the four additional herbs showed highly cooperative targeting patterns in the paralleled and cross-talked pathways related to inflammatory regulation and endocrine system, which may contribute to the additional relief of insomnia caused by inflammation, anxiety, or endocrine disorder. The interesting complementary mechanism we found among the herbal groups of SZRP may provide an example to study Chinese herbal formula and offers clues to future design of anti-insomnia strategy.

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