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1.
J Agric Food Chem ; 72(19): 10936-10943, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691835

RESUMO

RNAi plays a crucial role in insect gene function research and pest control field. Nonetheless, the variable efficiency of RNAi across diverse insects and off-target effects also limited its further application. In this study, we cloned six essential housekeeping genes from Solenopsis invicta and conducted RNAi experiments by orally administering dsRNA. Then, we found that mixing with liposomes significantly enhanced the RNAi efficiency by targeting for SiV-ATPaseE. Additionally, we observed a certain lethal effect of this dsRNA on queens by our established RNAi system. Furthermore, no strict sequence-related off-target effects were detected. Finally, the RNAi effect of large-scale bacteria expressing dsRNA was successfully confirmed for controlling S. invicta. In summary, this study established an RNAi system for S. invicta and provided a research template for the future development of nucleic acid drugs based on RNAi.


Assuntos
Formigas , Proteínas de Insetos , Interferência de RNA , Animais , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Formigas/genética , Controle de Insetos/métodos , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , Controle Biológico de Vetores/métodos , Feminino , Formigas Lava-Pés
2.
World J Gastrointest Oncol ; 16(5): 1725-1736, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764838

RESUMO

Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.

3.
Plant Dis ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568787

RESUMO

Stem rot caused by Sclerotinia sclerotiorum is a serious, and sometimes devastating, disease of lupin (Lupinus spp.). Two hundred and thirty-six lupin accessions from across 12 Lupinus species were screened against the prevalent S. sclerotiorum isolate MBRS-1 (pathotype 76). L. angustifolius accession 21655 and L. albus var. albus accession 20589 showed immune and 'near-immune' responses, respectively. Thirteen accessions of L. angustifolius, three accessions each of L. albus and L. albus var. albus, and a single accession each of L. albus var. graecus, L. mutabilis, L. palaestinus and L. pilosus (totalling ~4%) showed a highly resistant (HR) response. A further 19 accessions of L. angustifolius, two accessions each of L. albus and L. pilosus, and a single accession of L. mutabilis (totalling ~10%) showed a resistant (R) response. The reactions of 16 (15 L. angustifolius, one L. digitatus) of these 236 accessions were also compared with their reactions to a different isolate, WW-3 (pathotype 10). Against this isolate, five L. angustifolius accessions showed a HR response and four showed a R response, and the L. digitatus accession showed a moderate resistance (MR) response. Overall, isolate WW-3 caused significantly (P<0.05) smaller lesions than MBRS-1 across tested accessions in common. In addition, 328 plants in a 'wild' naturalized field population of L. cosentini were screened in situ in the field against isolate MBRS-1. Five (~1.5%) of the 328 plants of wild lupin showed an immune response, 63 (~19%) showed a HR response, and 146 (~45%) showed a R response. We believe this is the first examination of diverse Lupinus spp. germplasm responses to a prevalent pathotype of S. sclerotiorum. Lupin genotypes exhibiting high level resistance to Sclerotinia stem rot identified in this study can now be used as parental lines for crosses in lupin breeding programs and/or directly as improved cultivars to reduce the adverse impact of this disease on lupin crops.

4.
Insects ; 15(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535357

RESUMO

Endoparasitoids are insects that develop within other insects, employing unique strategies to enhance their offspring's survival. They inject polydnavirus and/or venom into their hosts along with eggs, effectively suppressing the host's immune system. Polydnavirus from Braconidae and Ichneumonidae wasps can integrate into the host's genome to express viral genes using the host's transcription systems. However, the ability of parasitoids without polydnavirus to manipulate host gene expression remains unclear. Lysine acetylation (LysAc), a post-translational modification critical for gene regulation, is hypothesized to be used by endoparasitoids lacking polydnavirus. We utilized the Chalcidoidea wasp Tetrastichus brontispae, which lacks polydnavirus, as an idiobiont endoparasitoid model to test this hypothesis, with pupae of the nipa palm hispid beetle Octodonta nipae as the host. Parasitism by T. brontispae resulted in the reduced expression of histone deacetylase Rpd3 and elevated levels of LysAc modification at histones H3.3K9 and H3.3K14 through proteomics and LysAc modification omics. The knockdown of Rpd3 increased the expression level of OnPPAF1 and OnPPO involved in the phenoloxidase cascade, leading to melanization in the host body whereby it resembled a mummified parasitized pupa and ultimately causing pupa death. This study enhances our understanding of how endoparasitoids employ histone acetylation to regulate immunity-related genes, offering valuable insights into their survival strategies.

5.
NPJ Biofilms Microbiomes ; 10(1): 25, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509085

RESUMO

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.


Assuntos
Hiperuricemia , Lacticaseibacillus rhamnosus , Humanos , Hiperuricemia/terapia , Nucleosídeos , Lactobacillus , Prolina , Purinas
6.
Anal Chim Acta ; 1296: 342332, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401940

RESUMO

Isoniazid (INH) is crucial in the treatment of tuberculosis; however, its overuse may induce significant gastrointestinal and hepatic side effects. On October 27, 2017, the International Agency for Research on Cancer, under the auspices of the World Health Organization, published a list of carcinogens for preliminary collation and reference. Isoniazid was categorized as a Group 3 carcinogen. The efficient detection of INH poses an important and challenging task. In this study, a "synergistic effect" is incorporated into the pillar (Yamagishi and Ogoshi, 2018) [5] arene-based macrocyclic host (DPA) by strategically attaching bis-p-hydroxybenzoic acid groups to the opposite ends of the pillar (Yamagishi and Ogoshi, 2018) [5] arene. This combination endows DPA with a reversible and selective fluorescence response to isoniazid. Additionally, DPA exhibits excellent analytical capabilities for isoniazid, including speed and selectivity, with a detection limit as low as 4.85 nM. Concurrently, DPA can self-assemble into a microsphere structure, which is convertible into micrometer-sized tubular structures through host-guest interactions with isoniazid. The introduction of a competitive guest, trimethylamine, enables the reversion to its microsphere structure. Consequently, this study presents an innovative and straightforward synthetic approach for smart materials that facilitates the reversible morphological transition between microspheres and microtubes in response to external chemical stimuli. This discovery provides a valuable strategy for designing "synergistic effects" in constructing trace-level isoniazid-responsive interfaces, with potential applications across various fields, such as controlled drug delivery.


Assuntos
Materiais Inteligentes , Isoniazida , Sistemas de Liberação de Medicamentos , Microesferas
7.
Tissue Cell ; 87: 102317, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330771

RESUMO

OBJECTIVE: To investigate the mechanism of Anwei decoction (AWD) intervention on gastric intestinal metaplasia (GIM) using a rat model through the endoplasmic reticulum stress-autophagy pathway. METHODS: Gastric intestinal metaplasia was induced in rats using 1-methyl-3-nitro-1-nitrosoguanidine. The experiment included a normal control group, a model group, and low-, medium- and high-dose AWD groups. The specificity of intestinal epithelial cells was determined for model establishment and drug efficacy by detecting the protein expression of markers such as MUC2, VILLIN and CDX2 through western blotting (WB). The effects of AWD on endoplasmic reticulum stress and autophagy were evaluated by measuring the mRNA and protein expression levels of endoplasmic reticulum stress markers (PEPK, ATF6, CHOP and caspase-12) and autophagy markers (LC3Ⅱ and Beclin-1) using reverse transcription polymerase chain reaction and the WB method. Furthermore, the ultrastructure of gastric mucosal cells and autophagosome status were observed using transmission electron microscopy. RESULTS: Compared with the model group, the AWD-treated rats exhibited significant improvement in body weight (P < 0.01), reduced protein expression of the intestine epithelial cell-specific markers MUC2, VILLIN, CDX2 and KLF4 (P < 0.01 for all) and increased SOX2 protein expression (P < 0.01). In addition, AWD suppressed the mRNA and protein expression of endoplasmic reticulum stress markers PEPK and ATF6 (P < 0.01 for all) and promoted the mRNA and protein expression of autophagy and apoptosis markers CHOP, caspase-12, LC3Ⅱ and Beclin-1 (P < 0.01 for all). CONCLUSION: Anwei decoction effectively inhibits the further progression of GIM and prevents the occurrence of gastric mucosal carcinogenesis.


Assuntos
Apoptose , Transdução de Sinais , Ratos , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/farmacologia , Caspase 12 , RNA Mensageiro , Autofagia , Estresse do Retículo Endoplasmático , Metaplasia
8.
Insects ; 15(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38249041

RESUMO

Symbiotic systems are intimately integrated at multiple levels. Host-endosymbiont metabolic complementarity in amino acid biosynthesis is especially important for sap-feeding insects and their symbionts. In weevil-Nardonella endosymbiosis, the final step reaction of the endosymbiont tyrosine synthesis pathway is complemented by host-encoded aminotransferases. Based on previous results from other insects, we suspected that these aminotransferases were likely transported into the Nardonella cytoplasm to produce tyrosine. Here, we identified five aminotransferase genes in the genome of the red palm weevil. Using quantitative real-time RT-PCR, we confirmed that RfGOT1 and RfGOT2A were specifically expressed in the bacteriome. RNA interference targeting these two aminotransferase genes reduced the tyrosine level in the bacteriome. The immunofluorescence-FISH double labeling localization analysis revealed that RfGOT1 and RfGOT2A were present within the bacteriocyte, where they colocalized with Nardonella cells. Immunogold transmission electron microscopy demonstrated the localization of RfGOT1 and RfGOT2A in the cytosol of Nardonella and the bacteriocyte. Our data revealed that RfGOT1 and RfGOT2A are transported into the Nardonella cytoplasm to collaborate with genes retained in the Nardonella genome in order to synthesize tyrosine. The results of our study will enhance the understanding of the integration of host and endosymbiont metabolism in amino acid biosynthesis.

9.
J Clin Invest ; 134(4)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175724

RESUMO

The mechanisms behind a lack of efficient fear extinction in some individuals are unclear. Here, by employing a principal components analysis-based approach, we differentiated the mice into extinction-resistant and susceptible groups. We determined that elevated synapsin 2a (Syn2a) in the infralimbic cortex (IL) to basolateral amygdala (BLA) circuit disrupted presynaptic orchestration, leading to an excitatory/inhibitory imbalance in the BLA region and causing extinction resistance. Overexpression or silencing of Syn2a levels in IL neurons replicated or alleviated behavioral, electrophysiological, and biochemical phenotypes in resistant mice. We further identified that the proline-rich domain H in the C-terminus of Syn2a was indispensable for the interaction with synaptogyrin-3 (Syngr3) and demonstrated that disrupting this interaction restored extinction impairments. Molecular docking revealed that ritonavir, an FDA-approved HIV drug, could disrupt Syn2a-Syngr3 binding and rescue fear extinction behavior in Syn2a-elevated mice. In summary, the aberrant elevation of Syn2a expression and its interaction with Syngr3 at the presynaptic site were crucial in fear extinction resistance, suggesting a potential therapeutic avenue for related disorders.


Assuntos
Medo , Córtex Pré-Frontal , Animais , Camundongos , Extinção Psicológica/fisiologia , Medo/fisiologia , Simulação de Acoplamento Molecular , Córtex Pré-Frontal/metabolismo , Sinapsinas/genética , Sinapsinas/metabolismo , Sinaptogirinas/metabolismo
10.
Pest Manag Sci ; 80(4): 1930-1939, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38072905

RESUMO

BACKGROUND: The fall armyworm, Spodoptera frugiperda, is one of the most dangerous pests to various crops. As the most crucial sugar crop, sugarcane is also constantly threatened by these pests. Plant wound-induced proteinase inhibitors (WIP) are natural defense proteins that play important roles in the defense system against insect attack. Breeding for resistance would be the best way to improve the variety characteristics and productivity of sugarcane. Screening and verification for potential plant endogenous insect-resistant genes would greatly improve the insect-resistant breeding progress of sugarcane. RESULTS: A sugarcane WIP5 gene (ScWIP5) was up-regulated 536 times after insect feeding treatment on previous published transcriptome databases. ScWIP5 was then cloned and its potential role in sugarcane resistance to fall armyworm evaluated by construction of transgenic Nicotiana benthamiana. The toxicity of ScWIP5 transgenic N. benthamiana to fall armyworm showed lower weight gain and higher mortality compared to wild-type N. benthamiana feeding group. Furthermore, the concentration of JA and NbAOC, NbAOS, and NbLOX from the Jasmin acid biosynthesis pathway was significantly induced in ScWIP5 transgenic N. benthamiana compared to the control. In addition, digestive enzyme actives from the insect gut were also evaluated, and trypsin and cathepsin were significantly lower in insects fed with ScWIP5 transgenic N. benthamiana. CONCLUSION: These results indicate that ScWIP5 might enhance insect resistance by increasing JA signal transduction processes and reducing insect digestive enzyme activities, thus impacting insect growth and development. © 2023 Society of Chemical Industry.


Assuntos
Saccharum , Animais , Spodoptera , Larva , Saccharum/genética , Melhoramento Vegetal , Genes de Plantas , Zea mays/genética
11.
13.
Front Immunol ; 14: 1196434, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077406

RESUMO

The herb Prunella vulgaris has shown significant immune-stimulatory and anti-inflammatory effects in mouse models. Here, the effects of a novel Prunella vulgaris-containing herbal mixture, PV-1, were examined in several mouse models for cancer, including chemically induced models of lung and oral cancers as well as syngraft models for lung cancer and melanoma. PV-1, consisting of extracts from Prunella vulgaris, Polygonum bistorta, Sonchus brachyotus and Dictamnus dasycarpus, exhibited no toxicity in a dose escalation study in A/J mice. PV-1 significantly inhibited mouse lung tumor development induced by the lung carcinogens vinyl carbamate and benzo[a]pyrene. PV-1 also hindered the induction of oral squamous cell carcinomas in C57BL/6 mice caused by 4-nitroquinoline-1-oxide. Flow cytometry analysis showed that PV-1 increased the numbers of CD8+ tumor-infiltrating lymphocytes (TILs) and increased the production of granzyme B, TNF-α, and IFN-γ by CD8+ TILs. PV-1 also suppressed granulocytic myeloid-derived suppressor cell numbers (g-MDSCs) and improved the anti-cancer activity of anti-PD-1 immunotherapy. These results indicate that PV-1 remodels the tumor immune microenvironment by selectively inhibiting g-MDSCs and increasing CD8+ TILs within tumors, resulting in decreased immune suppression and enhanced cancer chemopreventive efficacy.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Neoplasias Bucais , Prunella , Camundongos , Animais , Camundongos Endogâmicos C57BL , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Quimioprevenção , Microambiente Tumoral
14.
Pharmaceuticals (Basel) ; 16(12)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38139793

RESUMO

Ruan Hua Tang (RHT) and Ruan Hua Fang (RHF) are two Chinese herbal mixtures that have been used in clinical cancer treatment for decades. This study validated our hypothesis that RHT and RHF can inhibit lung tumor development in the mouse model of Benzo(a)pyrene-induced lung tumorigenesis. An RHT oral solution was diluted to 9% and 18% in water. RHF was mixed into the diet at 15% and 30% of total food in the final doses. Two weeks after injecting BP into mice, we administered RHT and RHF for eighteen weeks. We found that 9% and 18% RHT reduced tumor multiplicity by 36.05% and 38.81% (both p < 0.05) and the tumor load by 27.13% and 55.94% (p < 0.05); 15% and 30% RHF inhibited tumor multiplicity by 12.75% and 39.84% (p < 0.01) and the tumor load by 18.38% and 61.68% (p < 0.05). Ki67 expressions in the 9% and 18% RHT groups were 19.55% and 11.51%, significantly lower than in the control (33.64%). The Ki67 levels in the 15% and 30% RHF groups were 15.56% and 14.04%, significantly lower than in the control (27.86%). Caspase 3 expressions in the 9% and 18% RHT groups were 5.24% and 7.32%, significantly higher than in the control (2.39%). Caspase 3 levels in the 15% and 30% RHF groups were 6.53% and 4.74%, significantly higher than in the control (2.07%). The bio-absorption was confirmed via a pharmacokinetic test. This study showed that RHT and RHF are safe and can inhibit lung tumor development, with anti-proliferative and pro-apoptotic effects.

16.
Inorg Chem ; 62(42): 17236-17240, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37816176

RESUMO

Considerable progress in the construction of efficient fluorescence-resonance energy transfer (FRET) systems has promoted the development of artificial energy transfer materials. However, despite recent advances, the exploration of efficient and easy strategies to fabricate novel supramolecular systems with FRET activities is still a challenge. Here, we report that a two-step FRET system was successfully achieved, driven by platinum metallacycle based host-guest interactions. The two-step FRET system is used for the preparation of a white-light-emitting diode and serves as a nanoreactor for the photosynthetic process. This work offers a strategy for the fabrication of FRET systems and opens opportunities for functional materials constructed by platinum(II) metallacycle based host-guest interactions.

17.
NPJ Precis Oncol ; 7(1): 108, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880313

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has a poor prognosis. TOP2A is a key enzyme in DNA replication and is a therapeutic target for breast and other cancers. TOP2A-specific Th1-promoting epitopes with optimal binding affinity to MHC II were identified using a combined scoring system. The multi-peptide TOP2A vaccine elicited a robust immunologic response in immunized mice, as demonstrated by the significant production of Th1 cytokines from immunized animals' splenocytes stimulated in vitro with TOP2A peptides. Anti-tumor efficacy of the TOP2A vaccine was demonstrated in a syngeneic TNBC mouse model, in which pre-graft preventive vaccination was associated with significantly decreased tumor growth as compared to adjuvant control. In a genetically engineered mouse (GEM) model of TNBC, vaccinated animals demonstrated a significant reduction in tumor incidence and average tumor volume compared to adjuvant control. Finally, we examined TCR sequences in CD4 tumor Infiltrating lymphocytes (TIL) from vaccinated mice and found that the TIL contained TCR sequences specific to the three vaccine peptides. These data indicate that our newly developed multi-peptide TOP2A vaccine is highly immunogenic, elicits TILs with vaccine specific TCRs, and is highly effective in preventing and intercepting TNBC development and progression in vivo.

18.
Expert Opin Ther Targets ; 27(10): 939-952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37736880

RESUMO

INTRODUCTION: Drugs targeting mitochondria are emerging as promising antitumor therapeutics in preclinical models. However, a few of these drugs have shown clinical toxicity. Developing mitochondria-targeted modified natural compounds and US FDA-approved drugs with increased therapeutic index in cancer is discussed as an alternative strategy. AREAS COVERED: Triphenylphosphonium cation (TPP+)-based drugs selectively accumulate in the mitochondria of cancer cells due to their increased negative membrane potential, target the oxidative phosphorylation proteins, inhibit mitochondrial respiration, and inhibit tumor proliferation. TPP+-based drugs exert minimal toxic side effects in rodents and humans. These drugs can sensitize radiation and immunotherapies. EXPERT OPINION: TPP+-based drugs targeting the tumor mitochondrial electron transport chain are a new class of oxidative phosphorylation inhibitors with varying antiproliferative and antimetastatic potencies. Some of these TPP+-based agents, which are synthesized from naturally occurring molecules and FDA-approved drugs, have been tested in mice and did not show notable toxicity, including neurotoxicity, when used at doses under the maximally tolerated dose. Thus, more effort should be directed toward the clinical translation of TPP+-based OXPHOS-inhibiting drugs in cancer prevention and treatment.


Mitochondria, which are the cell's powerhouse of energy, are functional in cancer cells. Inhibition of cancer cell respiration is associated with inhibition of cancer cell proliferation. Therefore, mitochondria have become a promising target for developing antitumor drugs to treat cancer. Several classes of drug molecules selectively target cancer cell mitochondria and inhibit mitochondrial respiration or oxidative phosphorylation (OXPHOS). A new class of OXPHOS-targeting drugs is emerging as a potential cancer therapeutic. One of the OXPHOS inhibitor drugs, IACS-010759, developed by investigators at MD Anderson Cancer Center, was tested in patients with acute myeloid leukemia. Patients who were administered the drug developed peripheral neuropathy and other complications (lactic acidosis), resulting in dose reduction. At lower doses, this drug was not effective. Subsequently, the clinical trial was terminated. The investigators then showed the same type of neurotoxicity using a mouse model. These findings were recently published. Thus, there is an urgent need to develop new OXPHOS inhibitors that do not have neurotoxicity in mice or humans.In this opinion article, we make a case that there are other triphenylphosphonium cation (TPP+)-based mitochondrial OXPHOS inhibitors (inhibiting both complex I and complex III) that are structural modifications of naturally occurring molecules or US FDA-approved drugs. These mitochondria-targeted drugs (MTDs) are as potent as IACS-010759 in cells and in preclinical models. Several TPP+-based MTDs have been tested in mice and did not exert neurotoxicity. TPP+-containing MTDs such as mitochondria-targeted coenzyme Q10 (MitoQ) have been tested in patients with Parkinson's disease, with no evidence of peripheral neuropathy or other toxicity (e.g., lactic acidosis). Other US FDA-approved drugs (metformin and atovaquone [ATO] or papaverine) are in clinical trials alone or in combination with other standard-of-care treatments (e.g., radiation therapy). We recommend that TPP+-based drugs that have been tested in preclinical models or in humans should undergo clinical trials in patients with cancer.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Camundongos , Animais , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Neoplasias/patologia , Sistemas de Liberação de Medicamentos , Antineoplásicos/efeitos adversos
19.
Heliyon ; 9(9): e19237, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674843

RESUMO

Identifying the molecular and genetic basis of resistance to Sclerotinia stem rot (Sclerotinia sclerotiorum) is critical for developing long-term and cost-effective management of this disease in rapeseed/canola (Brassica napus). Current cultural or chemical management options provide, at best, only partial and/or sporadic control. Towards this, a B. napus breeding population (Mystic x Rainbow), including the parents, F1, F2, BC1P1 and BC1P2, was utilized in a field study to determine the inheritance pattern of Sclerotinia stem rot resistance (based on stem lesion length, SLL). Broad sense heritability was 0.58 for SLL and 0.44 for days to flowering (DTF). There was a significant negative correlation between SLL and stem diameter (SD) (r = -0.39) and between SLL and DTF (r = -0.28), suggesting co-selection of SD and DTF traits, along with SLL, should assist in improving overall resistance. Non-additive genetic variance was evident for SLL, DTF, and SD. In a genome wide association study (GWAS), a significant quantitative trait locus (QTL) was identified for SLL. Several putative candidate marker trait associations (MTA) were located within this QTL region. Overall, this study has provided valuable new understanding of inheritance of resistance to S. sclerotiorum, and has identified QTL, MTAs and transgressive segregants with high-level resistances. Together, these will foster more rapid selection for multiple traits associated with Sclerotinia stem rot resistance, by enabling breeders to make critical choices towards selecting/developing cultivars with enhanced resistance to this devastating pathogen.

20.
Phys Chem Chem Phys ; 25(32): 21456-21467, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37539623

RESUMO

Based on cylindrical photonic crystals in one dimension, a multi-scale sensor device with a logic operation is being proposed. At the same time, it can satisfy the functions of refractive index (RI) and magnetic field detection. Under the modulation of an external magnetic field, sharp absorption peaks (APs) are obtained in the terahertz (THz) range. In a certain frequency range (AP value above 0.9), as the particular InSb layers are applied to two different magnetic fields, APs of the same frequency can be implemented to operate as XOR logic gates. The results show that with a change in the detected physical quantity, the frequency point of the corresponding AP also moves. Therefore, by adjusting the position of the AP, the magnetic field and RI can be sensed, and the device shows relatively excellent performance of 6879.88 and 6943.65 in terms of quality factor. In addition, the optimal performance of sensitivity, detection limit, and corresponding figure of merit is 0.01264(2πc/d0) T-1, 2.25 × 10-4 T, 227.23 T-1, and -0.003779(2πc/d0) RIU-1, 7.69 × 10-3 RIU, 67.74 RIU-1. In terms of overall sensors, the proposed device is highly innovative in structure and meets the requirements of multi-scale measurements.

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