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1.
ACS Nano ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39088743

RESUMO

How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The resistance mechanism of platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis and develop resistance to chemotherapy drugs through metabolic variability. In addition, due to the lack of histone protection and a relatively weak damage repair ability, mitochondrial DNA (mtDNA) is more susceptible to damage, which in turn affects mitochondrial OXPHOS and can become a potential target for platinum-based drugs. Therefore, mitochondria, as targets of anticancer drugs, have become a hot topic in tumor resistance research. This study constructed a self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. ß-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles can target CD44 on the tumor surface and further deliver the prodrug to intracellular mitochondria through a triphenylphosphine group (TPP+). Disulfide bonds can be selectively degraded by glutathione (GSH) in mitochondria, releasing lonidamine (LND) and the cisplatin prodrug (Pt(IV)). Under the action of GSH and ascorbic acid, Pt(IV) is further reduced to cisplatin (Pt(II)). Cisplatin can cause mtDNA damage, induce mitochondrial dysfunction and mitophagy, and then affect mitochondrial OXPHOS. Meanwhile, LND can reduce the hexokinase II (HK II) level, induce destruction of mitochondria, and block energy supply by glycolysis inhibition. Ultimately, this self-assembled nano targeted delivery system can synergistically kill cisplatin-resistant lung cancer cells, which supplies an overcome cisplatin resistance choice via the disrupt mitochondria therapy.

2.
J Inflamm Res ; 17: 4229-4245, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979432

RESUMO

Background: This study aimed to discover diagnostic and prognostic biomarkers for sepsis immunotherapy through analyzing the novel cellular death process, cuproptosis. Methods: We used transcriptome data from sepsis patients to identify key cuproptosis-related genes (CuRGs). We created a predictive model and used the CIBERSORT algorithm to observe the link between these genes and the septic immune microenvironment. We segregated sepsis patients into three subgroups, comparing immune function, immune cell infiltration, and differential analysis. Single-cell sequencing and real-time quantitative PCR were used to view the regulatory effect of CuRGs on the immune microenvironment and compare the mRNA levels of these genes in sepsis patients and healthy controls. We established a sepsis forecast model adapted to heart rate, body temperature, white blood cell count, and cuproptosis key genes. This was followed by a drug sensitivity analysis of cuproptosis key genes. Results: Our results filtered three key genes (LIAS, PDHB, PDHA1) that impact sepsis prognosis. We noticed that the high-risk group had poorer immune cell function and lesser immune cell infiltration. We also discovered a significant connection between CuRGs and immune cell infiltration in sepsis. Through consensus clustering, sepsis patients were classified into three subgroups. The best immune functionality and prognosis was observed in subgroup B. Single-cell sequencing exposed that the key genes manage the immune microenvironment by affecting T cell activation. The qPCR results highlighted substantial mRNA level reduction of the three key genes in the SP compared to the HC. The prediction model, which combines CuRGs and traditional diagnostic indicators, performed better in accuracy than the other markers. The drug sensitivity analysis listed bisphenol A as highly sensitive to all the key genes. Conclusion: Our study suggests these CuRGs may offer substantial potential for sepsis prognosis prediction and personalized immunotherapy.

3.
Medicine (Baltimore) ; 103(25): e38543, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905431

RESUMO

BACKGROUND: Fibrolipoma of the lower lip is an uncommon condition with limited documentation in the literature. This paper provides updated insights into oral and maxillofacial lipomas through a detailed case report and comprehensive literature review, discussing clinical features, pathogenesis, diagnostic approaches, histopathology, and therapeutic strategies. CASE PRESENTATION: A 54-year-old female presented with a painless, enlarging mass on the inner aspect of her right lower lip, first noticed 2 years prior. The mass, now the size of a peanut, interfered with her eating and speech. Physical examination revealed a 2.0 × 2.5 × 1.0 cm mass beneath the mucous membrane of the right lower lip. It was firm, well-demarcated, and mobile. Surgical excision was performed, and histopathological analysis confirmed the diagnosis of a lower lip fibrolipoma. The lesion was successfully removed without recurrence. CONCLUSION: Lipomas in the oral and maxillofacial regions are rare, slow-growing benign tumors, particularly within the lips. Although their diagnosis is straightforward based on clinical presentation, histopathological confirmation is essential. Surgical resection remains the treatment of choice, with excellent prognostic outcomes.


Assuntos
Neoplasias Labiais , Lipoma , Humanos , Feminino , Pessoa de Meia-Idade , Lipoma/diagnóstico , Lipoma/cirurgia , Lipoma/patologia , Neoplasias Labiais/patologia , Neoplasias Labiais/cirurgia , Neoplasias Labiais/diagnóstico , Lábio/patologia , Lábio/cirurgia
4.
Artigo em Inglês | MEDLINE | ID: mdl-38940790

RESUMO

Background: Trigeminal neuralgia (TN), characterized by severe facial pain, warrants effective perioperative care. There is a critical need for evidence-based perioperative nursing interventions to enhance outcomes and well-being in patients undergoing microballoon compression for trigeminal neuralgia. Objective: This study aims to investigate the impact of standardized nursing during the perioperative period of microballoon compression in patients with trigeminal neuralgia (TN). Methods: A total of 22 TN patients admitted to our hospital from December 2021 to December 2022 underwent microballoon compression treatment. The control group (CG) received standard neurosurgical routine nursing, while the observation group (OG) received standardized nursing during the perioperative period. Comparative analysis included assessments of pain intensity, psychological status, sleep quality, overall quality of life, incidence of complications, and patient satisfaction. Results: Following nursing interventions, both groups exhibited a decrease in scores on the Neuropathic Pain Scale (NPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Pittsburgh Sleep Quality Index (PSQI). The OG demonstrated significantly lower scores compared to the CG (P < .05). Post-nursing, SF-36 scores decreased in both groups, with the OG displaying lower scores than the CG (P < .05). Although complications were less frequent in the OG, and patient satisfaction was higher, these differences were not statistically significant (P > .05). Conclusions: The implementation of standardized nursing during the perioperative period of microballoon compression in TN patients resulted in reduced pain intensity, improved psychological well-being, enhanced sleep quality, and better overall quality of life. These findings suggest the intervention's potential for valuable clinical application and merit further promotion.

5.
Biomater Sci ; 12(12): 3003-3026, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38695621

RESUMO

Janus structure hydrogels (JSHs) are novel materials. Their primary fabrication methods and various applications have been widely reported. JSHs are primarily composed of Janus particles (JNPs) and polysaccharide components. They exhibit two distinct physical or chemical properties, generating intriguing characteristics due to their asymmetric structure. Normally, one side (adhesive interface) is predominantly constituted of polysaccharide components, primarily serving excellent adhesion. On the other side (functional surface), they integrate diverse functionalities, concurrently performing a plethora of synergistic functions. In the biomedical field, JSHs are widely applied in anti-adhesion, drug delivery, wound healing, and other areas. It also exhibits functions in seawater desalination and motion sensing. Thus, JSHs hold broad prospects for applications, and they possess significant research value in nanotechnology, environmental science, healthcare, and other fields. Additionally, this article proposes the challenges and future work facing these fields.


Assuntos
Hidrogéis , Hidrogéis/química , Hidrogéis/farmacologia , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Animais , Polissacarídeos/química , Sistemas de Liberação de Medicamentos , Cicatrização/efeitos dos fármacos
6.
ACS Nano ; 18(20): 12820-12829, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38722145

RESUMO

Developing highly efficient catalysts, characterized by controllable pore architecture and effective utilization of active sites, is paramount in addressing the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs), which, however, remains a formidable challenge. In this study, a hierarchical porous catalytic metal-organic framework (HPC-MOF) with both appropriate porosity and abundant exposed catalytic sites is achieved through time-controlled precise pore engineering. It is revealed that the evolution of the porous structure and catalytic site density is time-dependent during the etching processes. The moderately etched HPC-MOF-M attains heterogeneous pores at various scales, where large apertures ensure fast mass transfer and micropores inherit high-density catalytic sites, enhancing utilization and catalytic kinetics at internal catalytic sites. Capitalizing on these advantages, LSB incorporating the HPC-MOF-M interlayer demonstrates a 164.6% improvement in discharge capability and an 83.3% lower decay rate over long-term cycling at 1.0C. Even under high sulfur loading of 7.1 mg cm-2 and lean electrolyte conditions, the LSB exhibits stable cycling for over 100 cycles. This work highlights the significance of balancing the relationship between mass transfer and catalytic sites through precise chemical regulation of the porous structure in catalytic MOFs, which are anticipated to inspire the development of advanced catalysts for LSBs.

7.
PLoS One ; 19(4): e0302367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38683798

RESUMO

The mesoscale eddy characteristics of the Mozambique Warm Current were investigated by detecting and tracking satellite altimetry data from 2010 to 2019. A total of 1,086 eddies were identified in the Mozambique Channel, comprising 509 cyclonic eddies and 577 anticyclonic eddies. The results revealed that the bay area on the northwest coast of Madagascar was the main hotspot of eddy generation, and the mean amplitude and radius of the anticyclonic eddies in the Mozambique Channel were 24.23 cm and 82.7 km, respectively, which are larger than those of the cyclonic eddies. Local wind forcing had a significant impact on the formation of mesoscale eddies in the Mozambique Channel. In winter, the wind stress in the northern and southern areas of the Mozambique Channel exhibited a strong correlation with the distribution of eddy kinetic energy (EKE), where both monsoonal winds in the north and trade winds in the south could facilitate mesoscale anticyclonic eddy formation. In addition, the variability in the number of anticyclonic and cyclonic eddies in the Mozambique Channel may have exerted a significant influence on the seasonal anomalous fluctuations in local sea surface temperatures (SSTs). This study presented a novel analysis of the mesoscale eddy characteristics in the Mozambique Channel.


Assuntos
Estações do Ano , Vento , Moçambique , Madagáscar , Tempestades Ciclônicas
8.
Bioorg Chem ; 147: 107319, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38593529

RESUMO

Reactivating p53 activity to restore its anticancer function is an attractive cancer treatment strategy. In this study, we designed and synthesized a series of novel PROTACs to reactivate p53 via the co-degradation of CK1α and CDK7/9 proteins. Bioactivity studies showed that the selected PROTAC 13i exhibited potency antiproliferative activity in MV4-11 (IC50 = 0.096 ± 0.012 µM) and MOLM-13 (IC50 = 0.072 ± 0.014 µM) cells, and induced apoptosis of MV4-11 cells. Western-blot analysis showed that PROTAC 13i triple CK1α and CDK7/9 protein degradation resulted in the significantly increased expression of p53. At the same time, the transcriptional repression due to the degradation significantly reduced downstream gene expression of MYC, MDM2, BCL-2 and MCL-1, and reduced the inflammatory cytokine levels of TNF-α, IL-1ß and IL-6 in PMBCs. These results indicate the beneficial impact of simultaneous CK1α and CDK7/9 degradation for acute myeloid leukemia therapy.


Assuntos
Antineoplásicos , Caseína Quinase Ialfa , Proliferação de Células , Quinase 9 Dependente de Ciclina , Quinases Ciclina-Dependentes , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia Mieloide Aguda , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Caseína Quinase Ialfa/metabolismo , Caseína Quinase Ialfa/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/metabolismo , Relação Estrutura-Atividade , Estrutura Molecular , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Linhagem Celular Tumoral , Proteólise/efeitos dos fármacos , Células Tumorais Cultivadas , Quimera de Direcionamento de Proteólise , Quinase Ativadora de Quinase Dependente de Ciclina
9.
Proc Natl Acad Sci U S A ; 121(16): e2318783121, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38588412

RESUMO

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.


Assuntos
Hemípteros , MicroRNAs , Oryza , Animais , Interferência de RNA , MicroRNAs/genética , MicroRNAs/metabolismo , Saliva , Hemípteros/fisiologia , Imunidade Vegetal/genética , Oryza/genética
10.
Sci Rep ; 14(1): 5273, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438400

RESUMO

Pancreatic cancer is a commonly occurring malignant tumor, with pancreatic ductal carcinoma (PDAC) accounting for approximately 95% of cases. According of its poor prognosis, identifying prognostic factors of pancreatic ductal carcinoma can provide physicians with a reliable theoretical foundation when predicting patient survival. This study aimed to analyze the impact of marital status on survival outcomes of PDAC patients using propensity score matching and machine learning. The goal was to develop a prognosis prediction model specific to married patients with PDAC. We extracted a total of 206,968 patient records of pancreatic cancer from the SEER database. To ensure the baseline characteristics of married and unmarried individuals were balanced, we used a 1:1 propensity matching score. We then conducted Kaplan-Meier analysis and Cox proportional-hazards regression to examine the impact of marital status on PDAC survival before and after matching. Additionally, we developed machine learning models to predict 5-year CSS and OS for married patients with PDAC specifically. In total, 24,044 PDAC patients were included in this study. After 1:1 propensity matching, 8043 married patients and 8,043 unmarried patients were successfully enrolled. Multivariate analysis and the Kaplan-Meier curves demonstrated that unmarried individuals had a poorer survival rate than their married counterparts. Among the algorithms tested, the random forest performed the best, with 0.734 5-year CSS and 0.795 5-year OS AUC. This study found a significant association between marital status and survival in PDAC patients. Married patients had the best prognosis, while widowed patients had the worst. The random forest is a reliable model for predicting survival in married patients with PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/diagnóstico , Estado Civil , Casamento , Neoplasias Pancreáticas/diagnóstico , Aprendizado de Máquina
11.
Aesthetic Plast Surg ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532201

RESUMO

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

13.
Angew Chem Int Ed Engl ; 63(8): e202318859, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38179841

RESUMO

The development of highly efficient catalysts to address the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs) remains a formidable challenge. In this study, a series of multi-site catalytic metal-organic frameworks (MSC-MOFs) were elaborated through multimodal molecular engineering to regulate both the reactant diffusion and catalysis processes. MSC-MOFs were crafted with nanocages featuring collaborative specific adsorption/catalytic interfaces formed by exposed mixed-valence metal sites and surrounding adsorption sites. This design facilitates internal preconcentration, a coadsorption mechanism, and continuous efficient catalytic conversion toward polysulfides concurrently. Leveraging these attributes, LSBs with an MSC-MOF-Ti catalytic interlayer demonstrated a 62 % improvement in discharge capacity and cycling stability. This resulted in achieving a high areal capacity (11.57 mAh cm-2 ) at a high sulfur loading (9.32 mg cm-2 ) under lean electrolyte conditions, along with a pouch cell exhibiting an ultra-high gravimetric energy density of 350.8 Wh kg-1 . Lastly, this work introduces a universal strategy for the development of a new class of efficient catalytic MOFs, promoting SRR and suppressing the shuttle effect at the molecular level. The findings shed light on the design of advanced porous catalytic materials for application in high-energy LSBs.

14.
PLoS One ; 18(11): e0292728, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37917656

RESUMO

An intense tropical cyclone (TC), TC Hellen, occurred in the northern Mozambique Channel on March 27, 2014, and moved from the east coast of the African continent to the northern Madagascar island. TC Hellen dramatically altered the marine environment in the northern Mozambique Channel, resulting in a significant chlorophyll-a (Chl-a) bloom. A giant surface Chl-a northwest-ward movement from the northwest coast of Madagascar Island was first observed after the passage of TC Hellen in the northern Mozambique Channel. The dynamic mechanisms of these phenomenon were studied by satellite remote sensing, multisource reanalysis data, and Argo float data. The results show that transient northwestward-moving eddies, upwelling, and winds had important effects on the Chl-a bloom and its northwestward movement. Ekman transport driven by coastal southeasterly winds entrained waters with high Chl-a concentrations to the northwest, while TC Hellen enhanced cyclonic eddy upwelling and uplifted nutrient-rich deep water to the upper ocean. This vertical mixing and upwelling in turn triggered the Chl-a bloom in the offshore surface layer. This study provides insight into the reflection of phytoplankton dynamics by TCs in the northern Mozambique Channel.


Assuntos
Tempestades Ciclônicas , Moçambique , Clorofila/análise , Clorofila A , Fitoplâncton , Estações do Ano
15.
BMC Anesthesiol ; 23(1): 367, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946144

RESUMO

BACKGROUND: Sepsis is a life-threatening disease with a poor prognosis, and metabolic disorders play a crucial role in its development. This study aims to identify key metabolites that may be associated with the accurate diagnosis and prognosis of sepsis. METHODS: Septic patients and healthy individuals were enrolled to investigate metabolic changes using non-targeted liquid chromatography-high-resolution mass spectrometry metabolomics. Machine learning algorithms were subsequently employed to identify key differentially expressed metabolites (DEMs). Prognostic-related DEMs were then identified using univariate and multivariate Cox regression analyses. The septic rat model was established to verify the effect of phenylalanine metabolism-related gene MAOA on survival and mean arterial pressure after sepsis. RESULTS: A total of 532 DEMs were identified between healthy control and septic patients using metabolomics. The main pathways affected by these DEMs were amino acid biosynthesis, phenylalanine metabolism, tyrosine metabolism, glycine, serine and threonine metabolism, and arginine and proline metabolism. To identify sepsis diagnosis-related biomarkers, support vector machine (SVM) and random forest (RF) algorithms were employed, leading to the identification of four biomarkers. Additionally, analysis of transcriptome data from sepsis patients in the GEO database revealed a significant up-regulation of the phenylalanine metabolism-related gene MAOA in sepsis. Further investigation showed that inhibition of MAOA using the inhibitor RS-8359 reduced phenylalanine levels and improved mean arterial pressure and survival rate in septic rats. Finally, using univariate and multivariate cox regression analysis, six DEMs were identified as prognostic markers for sepsis. CONCLUSIONS: This study employed metabolomics and machine learning algorithms to identify differential metabolites that are associated with the diagnosis and prognosis of sepsis patients. Unraveling the relationship between metabolic characteristics and sepsis provides new insights into the underlying biological mechanisms, which could potentially assist in the diagnosis and treatment of sepsis. TRIAL REGISTRATION: This human study was approved by the Ethics Committee of the Research Institute of Surgery (2021-179) and was registered by the Chinese Clinical Trial Registry (Date: 09/12/2021, ChiCTR2200055772).


Assuntos
Metabolômica , Sepse , Animais , Humanos , Ratos , Biomarcadores/metabolismo , Metabolômica/métodos , Fenilalanina , Prognóstico , Sepse/diagnóstico , Sepse/metabolismo
16.
Biomater Sci ; 11(22): 7247-7267, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37794789

RESUMO

Exosomes are increasingly recognized as important effector molecules that regulate intercellular signaling pathways. Notably, certain types of exosomes can induce therapeutic responses, including cell proliferation, angiogenesis, and tissue repair. The use of exosomes in therapy is a hot spot in current research, especially in regenerative medicine. Despite the therapeutic potential, problems have hindered their success in clinical applications. These shortcomings include low concentration, poor targeting and limited loading capability. To fully realize their therapeutic potential, certain modifications are needed in native exosomes. In the present review, we summarize the exosome modification and functionalization strategies. In addition, we provide an overview of potential clinical applications and highlight the issues associated with the biosafety and biocompatibility of engineered exosomes in applications.


Assuntos
Exossomos , Exossomos/metabolismo , Contenção de Riscos Biológicos , Medicina Regenerativa
17.
Mol Biol Evol ; 40(10)2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37804524

RESUMO

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.


Assuntos
Afídeos , Hemípteros , Animais , Ferredoxinas/metabolismo , Plantas/metabolismo , Hemípteros/genética , Nicotiana/genética , Nicotiana/metabolismo , Afídeos/metabolismo , Proteínas e Peptídeos Salivares/genética
18.
Insects ; 14(9)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37754707

RESUMO

The bean bug, Riptortus pedestris (Hemiptera: Heteroptera), poses a significant threat to soybean production, resulting in substantial crop losses. Throughout the soybean cultivation period, these insects probe and suck on various parts of plants, including leaves, pods, and beans. However, the specific mechanisms by which they adapt to different food resources remain unknown. In this study, we conducted gut transcriptomic analyses of R. pedestris fed with soybean leaves, pods, and beans. A total of 798, 690, and 548 differently expressed genes (DEGs) were monitored in G-pod vs. G-leaf (comparison of insect feeding on pods and leaves), G-bean vs. G-leaf (comparison of insect feeding on beans and leaves), and G-pod vs. G-bean (comparison of insect feeding on pods and beans), respectively. When fed on pods and beans, there was a significant increase in the expression of digestive enzymes, particularly cathepsins, serine proteases, and lipases. Conversely, when soybean leaves were consumed, detoxification enzymes, such as ABC transporters and 4-coumarate-CoA ligase, exhibited higher expression. Our findings indicate that R. pedestris dynamically regulates different metabolic pathways to cope with varying food resources, which may contribute to the development of effective strategies for managing this pest.

19.
Pest Manag Sci ; 79(12): 4809-4818, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37483070

RESUMO

BACKGROUND: The bean bug, Riptortus pedestris, is known to cause significant economic losses in soybean crops due to its seed-sucking behavior, but the mechanism of its adaptation to lipid-rich seeds remains poorly understood. To exploit potential target genes for controlling this pest, neutral lipases are functionally characterized in this study. RESULTS: In this study, a total of 69 lipases were identified in R. pedestris, including 35 neutral lipases that underwent significant expansion. The phylogeny, expression patterns, and catalytic capacity of neutral lipases were investigated and we selected six salivary gland-specific, eight gut-specific, and three ovary-specific genes for functional analysis. All three ovary-specific neutral lipases (Chr1.3195, Chr1.0994, and Chr5.0087) are critical for insect reproduction, while a few gut-specific neutral lipases (Chr4.0221 and Chr1.3207) influence insect survivorship or weight gain. In contrast, no significant phenotype change is observed when silencing salivary gland-specific neutral lipases. CONCLUSION: The lipases Chr1.3195, Chr1.0994, Chr5.0087, Chr4.0221, and Chr1.3207 are essential for R. pedestris feeding and reproduction, and the insect is highly sensitive to their deficiency, suggesting that neutral lipases are promising candidates for application in RNAi-based control of this destructive pest. © 2023 Society of Chemical Industry.


Assuntos
Heterópteros , Animais , Feminino , Heterópteros/genética , Reprodução , Glycine max/genética , Sementes
20.
J Craniofac Surg ; 34(7): 2217-2221, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37365693

RESUMO

Fat tissue has been widely used as a filler material during plastic surgery, but unpredictable fat retention remains a significant concern. Fat tissue is vulnerable to ischemia and hypoxia, but it always has waiting time before injection in the operation theater. Apart from transferring fat tissue as quickly as possible after harvesting, washing the aspirate with cool normal saline is often used. However, the mechanisms of cool temperature acting on adipose tissue have yet to be fully elucidated. Herein, this study aims to explore the effect of preservation at different temperatures on the inflammatory profile of adipose tissue. Inguinal adipose tissue of rats was collected and cultured in vitro under 4°C, 10°C, and room temperature for 2 hours. The proportion of damaged adipocytes and an array of cytokines were determined. We observed that the damage rate of the adipocyte membrane was slightly higher at room temperature, but there was no significant difference, while we noticed increased IL-6 and MCP-1 levels in adipose tissue at room temperature ( P <0.01). The 4°C and 10°C cool temperatures may offer protection against proinflammatory states during the adipose tissue preserved in vitro.


Assuntos
Adipócitos , Tecido Adiposo , Ratos , Animais , Temperatura , Temperatura Baixa , Citocinas
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