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1.
Heliyon ; 10(8): e29635, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38699749

RESUMO

Rabbit (RM) has become a valuable source of nutrients since the 1970s, helping to transform the European food industry into the largest RM producer in the world. However, the RM industry is experiencing a critical period of ethical imbalance. This trend, described as feed conversion ratio, impacts the environmental and financial performance of RM farms, which could lead to an increase production of industrial waste. In addition, the loss of corporate ethical responsibility and sustainable development by RM-oriented companies has further exacerbated the situation. Our objective was to summarize current trends in the RM industry and markets, highlighting possible strengths and weaknesses. This review shows current approaches in sustainable techniques in RM production processes, ethical issue, environmental and processing responsibility of RM producers, as well as social responsibilities and ethical practices of slaughterhouses and RM producers, sustainable environmental practices of slaughterhouses, technological aspects and safety of RM and social drivers in RM market. The analysis of reviewed literature revealed the potential strategies for sustainable RM production.

2.
Sci Adv ; 10(18): eadn0172, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38691595

RESUMO

Collective cell dynamics is essential for tissue morphogenesis and various biological functions. However, it remains incompletely understood how mechanical forces and chemical signaling are integrated to direct collective cell behaviors underlying tissue morphogenesis. Here, we propose a three-dimensional (3D) mechanochemical theory accounting for biochemical reaction-diffusion and cellular mechanotransduction to investigate the dynamics of multicellular lumens. We show that the interplay between biochemical signaling and mechanics can trigger either pitchfork or Hopf bifurcation to induce diverse static mechanochemical patterns or generate oscillations with multiple modes both involving marked mechanical deformations in lumens. We uncover the crucial role of mechanochemical feedback in emerging morphodynamics and identify the evolution and morphogenetic functions of hierarchical topological defects including cell-level hexatic defects and tissue-level orientational defects. Our theory captures the common mechanochemical traits of collective dynamics observed in experiments and could provide a mechanistic context for understanding morphological symmetry breaking in 3D lumen-like tissues.


Assuntos
Mecanotransdução Celular , Modelos Biológicos , Morfogênese , Fenômenos Biomecânicos , Animais
3.
Int J Biol Macromol ; 270(Pt 1): 132265, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734346

RESUMO

Edible mushrooms are prone to deteriorate during storage. A Single chitosan film or coating has limitations in preservation. Therefore, this article focused on the improvement of modified chitosan-based films and coatings on properties related to storage quality of edible mushrooms (e.g.: safety, barrier, mechanical, antioxidant and antibacterial properties). Besides, the application of chitosan-based materials in the preservation of mushrooms was also discussed. The modified chitosan film and coating can slow down the respiration of mushrooms, inhibit the growth of microorganisms, protect antioxidant compositions, and regulate the activity of related enzymes, thus improving the quality and prolonging the shelf life of mushrooms. Meanwhile, the added ingredients improve the water and gas barrier properties of chitosan through volume and group occupation, and reduce the light transmittance of chitosan through light transmission, scattering and absorption. Essential oils and polyphenolic compounds had a better enhancement of antioxidant and antimicrobial properties of chitosan.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38639560

RESUMO

Rechargeable lithium-sulfur (Li-S) batteries are promising for high-energy storage. However, conventional redox reactions involving sulfur (S) and lithium (Li) can lead to unstable intermediates. Over the past decade, many strategies have emerged to address this challenge, enabling nonconventional electrochemical reactions in Li-S batteries. In our Perspective, we provide a brief review of these strategies and highlight their potential benefits. Specifically, our group has pioneered a top-down approach, investigating Li-S reactions at molecular and subatomic levels, as demonstrated in our recent work on stable S isotopes. These insights not only enhance understanding of charge transfer and storage properties but also offer exciting opportunities for advancements in battery materials research.

5.
Nat Commun ; 15(1): 3000, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589403

RESUMO

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. However, during cell expansion under mechanical stress, actomyosin networks are strengthened and polarized to relax stress. Thus, cells face a conflicting situation between the enhanced actomyosin contractile properties and the expansion behaviour of the cell or tissue. To address this paradoxical situation, we study late Drosophila oogenesis and reveal an unusual epithelial expansion wave behaviour. Mechanistically, Rac1 and Rho1 integrate basal pulsatile actomyosin networks with ruffles and focal adhesions to increase and then stabilize basal area of epithelial cells allowing their flattening and elongation. This epithelial expansion behaviour bridges cell changes to oocyte growth and extension, while oocyte growth in turn deforms the epithelium to drive cell spreading. Basal pulsatile actomyosin networks exhibit non-contractile mechanics, non-linear structures and F-actin/Myosin-II spatiotemporal signal separation, implicating unreported expanding properties. Biophysical modelling incorporating these expanding properties well simulates epithelial cell expansion waves. Our work thus highlights actomyosin expanding properties as a key mechanism driving tissue morphogenesis.


Assuntos
Actomiosina , Proteínas de Drosophila , Animais , Actomiosina/metabolismo , Proteínas de Drosophila/metabolismo , Células Epiteliais/metabolismo , Citoesqueleto de Actina/metabolismo , Drosophila/metabolismo , Epitélio/metabolismo , Morfogênese
6.
Int J Mol Sci ; 25(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38474082

RESUMO

The removal of Cr(VI), a highly-toxic heavy metal, from industrial wastewater is a critical issue in water treatment research. Photocatalysis, a promising technology to solve the Cr(VI) pollution problem, requires urgent and continuous improvement to enhance its performance. To address this need, an electric field-assisted photocatalytic system (PCS) was proposed to meet the growing demand for industrial wastewater treatment. Firstly, we selected PAF-54, a nitrogen-rich porous organic polymer, as the PCS's catalytic material. PAF-54 exhibits a large adsorption capacity (189 mg/g) for Cr(VI) oxyanions through hydrogen bonding and electrostatic interaction. It was then coated on carbon paper (CP) and used as the photocatalytic electrode. The synergy between capacitive deionization (CDI) and photocatalysis significantly promotes the photoreduction of Cr(VI). The photocatalytic performance was enhanced due to the electric field's influence on the mass transfer process, which could strengthen the enrichment of Cr(VI) oxyanions and the repulsion of Cr(III) cations on the surface of PAF-54/CP electrode. In addition, the PCS system demonstrates excellent recyclability and stability, making it a promising candidate for chromium wastewater treatment.


Assuntos
Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Águas Residuárias , Cromo/análise , Adsorção , Cinética , Concentração de Íons de Hidrogênio
7.
Artigo em Inglês | MEDLINE | ID: mdl-38498783

RESUMO

PURPOSE: To explore the contribution of paired-related homeobox 1-positive cells to the implant-induced osseointegration process in adult alveolar bone and the potential underlying mechanisms. MATERIALS AND METHODS: Cre recombinase-induced lineage tracing and cell ablation were conducted in a murine dental implant model. Scratch and transwell assays were used to assess MC3T3-E1 cell migration after paired-related homeobox 1 overexpression. Single-cell RNA sequencing were applied to identify potential genes involved in pairedrelated homeobox 1-positive cells-driven osteogenesis. RESULTS: Paired-related homeobox 1- positive cells were observed to accumulate in the peri-implant area in a time-dependent manner. The number of these cells were found to reach its maximum on day 14. Osseointegration in mice were noticeably impaired after ablation of paired-related homeobox 1-positive cells. Further, it was discovered that paired-related homeobox 1 promotes MC3T3- E1 cell migration, a process which is indispensable for sound healing of peri-implant tissue. Finally, Semaphorin 3C was detected exclusively and abundantly expressed by paired-related homeobox 1-positive cells. Knockdown of semaphorin 3C in paired-related homeobox 1- positive cells significantly weakened their osteogenic potential. CONCLUSION: Our data suggest that paired-related homeobox 1-positive cells contribute to the osseointegration process under stress stimulation and semaphorin 3C may play a critical role in paired-related homeobox 1- positive cell-driven osteogenesis. Paired-related homeobox 1 could significantly promote MC3T3-E1 cell migration.

8.
J Integr Med ; 22(1): 72-82, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38307819

RESUMO

OBJECTIVE: Melittin and its derivative have been developed to support effective gene delivery systems. Their ability to facilitate endosomal release enhances the delivery of nanoparticle-based gene therapy. Nevertheless, its potential application in the context of viral vectors has not received much attention. Therefore, we would like to optimize the rAAV vector by Melittin analog to improve the transduction efficiency of rAAV in liver cancer cells and explore the mechanism of Melittin analog on rAAV. METHODS: Various melittin-derived peptides were inserted into loop VIII of the capsid protein in recombinant adeno-associated virus vectors. These vectors carrying either gfp or fluc genes were subjected to quantitative polymerase chain reaction assays and transduction assays in human embryonic kidney 293 (HEK293T) cells to investigate the efficiency of vector production and gene delivery. In addition, the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice. Finally, the intricate details of the vector-mediated transduction mechanisms were explored by using pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle. RESULTS: A total of 76 melittin-related peptides were identified from existing literature. Among them, CMA-3, p5RHH and aAR3 were found to significantly inhibit transduction of rAAV2 vector crude lysate. The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV. Mechanistically, bafilomycin A1, a vacuolar endosome acidification inhibitor, completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors. Most importantly, p5RHH-rAAV8 vectors also increased hepatic transduction in vivo in C57BL/6 mice. CONCLUSION: The incorporation of melittin analogs into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression. While further modifications remain an area of interest, our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery. Please cite this article as: Meng J, He Y, Yang H, Zhou L, Wang S, Feng X, Al-shargi OY, Yu X, Zhu L, Ling, C. Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency. J Integr Med. 2024; 22(1): 72-82.


Assuntos
Dependovirus , Meliteno , Camundongos , Masculino , Animais , Humanos , Dependovirus/genética , Meliteno/farmacologia , Meliteno/genética , Transdução Genética , Células HEK293 , Camundongos Endogâmicos C57BL , Vetores Genéticos
9.
Microbiome ; 12(1): 20, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317217

RESUMO

BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.


Assuntos
Infecções por Coronavirus , Microbioma Gastrointestinal , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Doenças dos Suínos/prevenção & controle , Resistência à Doença
10.
Biochem Genet ; 62(2): 1087-1102, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37532836

RESUMO

Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites.

11.
Environ Sci Technol ; 58(1): 960-969, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38150269

RESUMO

SO2 reduction with CH4 to produce elemental sulfur (S8) or other sulfides is typically challenging due to high energy barriers and catalyst poisoning by SO2. Herein, we report that a comproportionation reaction (CR) induced by H2S recirculating significantly accelerates the reactions, altering reaction pathways and enabling flexible adjustment of the products from S8 to sulfides. Results show that SO2 can be fully reduced to H2S at a lower temperature of 650 °C, compared to the 800 °C required for the direct reduction (DR), effectively eliminating catalyst poisoning. The kinetic rate constant is significantly improved, with CR at 650 °C exhibiting about 3-fold higher value than DR at 750 °C. Additionally, the apparent activation energy decreases from 128 to 37 kJ/mol with H2S, altering the reaction route. This CR resolves the challenges related to robust sulfur-oxygen bond activation and enhances CH4 dissociation. During the process, the well-dispersed lamellar MoS2 crystallites with Co promoters (CoMoS) act as active species. H2S facilitates the comproportionation reaction, reducing SO2 to a nascent sulfur (Sx*). Subsequently, CH4 efficiently activates CoMoS in the absence of SO2, forming H2S. This shifts the mechanism from Mars-van Krevelen (MvK) in DR to sequential Langmuir-Hinshelwood (L-H) and MvK in CR. Additionally, it mitigates sulfation poisoning through this rapid activation reaction pathway. This unique comproportionation reaction provides a novel strategy for efficient sulfur resource utilization.


Assuntos
Metano , Dióxido de Enxofre , Metano/química , Sulfetos/química , Temperatura , Enxofre/química , Oxirredução
13.
ACS Nano ; 17(24): 24668-24684, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38091551

RESUMO

The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures. These hierarchical interfacial structures penetrate the cancer monolayer and can spontaneously segregate or even envelop cancer cell clusters, consistent with our theoretical prediction. By tracking the substrate displacements via embedded fluorescent nanobeads and implementing nanomechanical modeling that combines atomic force microscopy and finite element simulations, we computed mechanical force patterns, including traction forces and monolayer stresses, caused by the monolayer interaction. It is found that the heterogeneous mechanical forces accumulated in the monolayers are able to squeeze cancer cells, leading to three-dimensional interfacial bulges or cell extrusion, initiating the p53 apoptosis signaling pathways of cancer cells. We reveal that intercellular E-cadherin and P-cadherin of epithelial cells differentially regulate the interfacial organization including migration speed, directionality, spatial correlation, F-actin alignment, and subcellular protrusions of MCF10A cells; whereas E-cadherin governs interfacial geometry that is relevant to force localization and cancer cell extrusion, P-cadherin maintains interfacial integrity that enables long-range force transmission. Our findings suggest that the collaborative molecular and mechanical behaviors are crucial for preventing epithelial tissues from undergoing tumor invasion.


Assuntos
Caderinas , Neoplasias , Humanos , Caderinas/metabolismo , Actinas/metabolismo , Células Epiteliais/metabolismo , Adesão Celular
14.
Chin J Dent Res ; 26(4): 257-264, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126371

RESUMO

OBJECTIVE: To evaluate the effects of powered and manual tooth brushing on gingival inflammation in a Chinese population with mild to moderate gingivitis. METHODS: The present randomised, single-blind, parallel clinical trial was conducted in five cities in China. Generally healthy participants aged 18 to 65 years, who were non-smokers and had at least 20 sites of gingival bleeding, were included as eligible subjects. The subjects were randomly assigned to either the powered tooth brushing (PTB) group or standard manual tooth brushing (MTB) group. All subjects were supplied with a fluoride-containing toothpaste, Gingival Bleeding Index (GBI), Modified Gingival Index (MGI) and the Turesky modification of the Quigley-Hein Plaque Index (MPI) were used to evaluate the outcomes. RESULTS: A total of 235 subjects completed the study, 118 in the PTB group and 117 in the MTB group. The mean age and sex distribution for the PTB and MTB groups were 34.40 ± 9.99 years, 89 women and 29 men, and 34.20 ± 10.14 years, 82 women and 35 men, respectively. After 6 months, the percentage decrease in MGI was 26.150% ± 26.897% for the PTB group and 14.768% ± 38.544% for the MTB group (P = 0.0092). Statistically significant differences between types of tooth brushing were also observed at 6 months for GBI, and at all time points for MPI. CONCLUSION: Tooth brushing with a powered toothbrush twice a day was shown to be more effective than use of a manual toothbrush in reducing gingival inflammation, gingival bleeding and surface plaque after a 6-month period. Both kinds of toothbrushes were safe for the oral tissues.


Assuntos
Gengivite , Escovação Dentária , Feminino , Humanos , Masculino , China , Índice de Placa Dentária , Desenho de Equipamento , Hemorragia Gengival , Gengivite/prevenção & controle , Inflamação , Método Simples-Cego , Cremes Dentais , Adulto
15.
Mar Pollut Bull ; 197: 115695, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37951121

RESUMO

Floating marine debris (FMD) is a pervasive problem in marginal seas worldwide. Driven by the nearshore waves, the FMD gradually accumulates shoreward and has a large chance of being beached, posing a direct threat to the coastal environment. Thus, investigating the nearshore drifting and beaching process of the FMD is of paramount importance. In this article, the trajectories of the FMD on a sloping beach are simulated by the Smoothed Particle Hydrodynamics (SPH) method, which is pre-verified through laboratory experiments. A series of sensitivity tests are conducted numerically on the influence of attributes of FMD as well as varied wave height (H0), and wave period (T0) on its beaching process. It is found that the beaching process of the FMD can be divided into three steps: drifting in front of surf zones, surfing and leaping with plunging waves, and advancing via wave runup. The density of the FMD combined with wave steepness determines whether the FMD can enter into the surf zone where it has a large chance to beach. Finally, this article proposed a semi-analytical model with improved Morison's equations considering the second-order Lagrangian transport on a sloping beach. This semi-analytical model is much faster and is comparable in computational accuracy to the high-resolution SPH model. It has the potential to be incorporated into the existing marine models and replace the stochastic process assumed for the FMD's tracking in the nearshore, in order to achieve more accurate assessment on the stranded FMD.


Assuntos
Meio Ambiente , Monitoramento Ambiental , Oceanos e Mares , Hidrodinâmica , Plásticos
16.
Nutrients ; 15(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37960180

RESUMO

Carboxymethyl pachymaran (CMP) was treated via high-temperature and cellulase hydrolysis to obtain HTCMP, HTEC-24, and HTEC-48. The chemical structure and in vivo antitumor activities of the four types of CMPs were investigated. Compared with CMP (787.9 kDa), the molecular weights of HTCMP, HTEC-24, and HTEC-48 were decreased to 429.8, 129.9, and 68.6 kDa, respectively. The viscosities and particle sizes of the CMPs could also decrease with the decline in the molecular weights. All the CMPs showed antitumor abilities, but HTEC-24 exhibited the best activity. In the animal study, when curing the spleen and thymus, CMPs displayed immunomodulatory effects by increasing the secretion of IFN-γ and IL2 in mice. The CMPs also exerted an antitumor ability by regulating the gut microbiota in tumor-bearing mice. Our results established a foundation to develop an antitumor drug with CMP.


Assuntos
Antineoplásicos , Microbioma Gastrointestinal , Animais , Camundongos , Peso Molecular , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Glucanos/química
17.
Foods ; 12(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37835281

RESUMO

Flavor is the most important sensory quality in food [...].

18.
Nutrients ; 15(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37892435

RESUMO

Poria cocos is traditionally used as both food and medicine. Triterpenoids in Poria cocos have a wide range of pharmacological activities, such as diuretic, sedative and tonic properties. In this study, the anti-tumor activities of poricoic acid A (PAA) and poricoic acid B (PAB), purified by high-speed counter-current chromatography, as well as their mechanisms and signaling pathways, were investigated using a HepG2 cell model. After treatment with PAA and PAB on HepG2 cells, the apoptosis was obviously increased (p < 0.05), and the cell cycle arrested in the G2/M phase. Studies showed that PAA and PAB can also inhibit the occurrence and development of tumor cells by stimulating the generation of ROS in tumor cells and inhibiting tumor migration and invasion. Combined Polymerase Chain Reaction and computer simulation of molecular docking were employed to explore the mechanism of tumor proliferation inhibition by PAA and PAB. By interfering with phosphatidylinositol-3-kinase/protein kinase B, Mitogen-activated protein kinases and p53 signaling pathways; and further affecting the expression of downstream caspases; matrix metalloproteinase family, cyclin-dependent kinase -cyclin, Intercellular adhesion molecules-1, Vascular Cell Adhesion Molecule-1 and Cyclooxygenase -2, may be responsible for their anti-tumor activity. Overall, the results suggested that PAA and PAB induced apoptosis, halted the cell cycle, and inhibited tumor migration and invasion through multi-pathway interactions, which may serve as a potential therapeutic agent against cancer.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Triterpenos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Triterpenos/farmacologia , Simulação de Acoplamento Molecular , Simulação por Computador , Proliferação de Células , Transdução de Sinais , Apoptose
19.
Molecules ; 28(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37687209

RESUMO

The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10-12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2-5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC50 values as low as 5.82 ± 0.18 µM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions.


Assuntos
Agaricales , Diterpenos , Animais , Ratos , Simulação de Acoplamento Molecular , Diterpenos/farmacologia
20.
iScience ; 26(10): 107864, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37766982

RESUMO

The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.

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