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1.
Proc Natl Acad Sci U S A ; 121(25): e2406788121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38865267

RESUMO

Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia. This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species.


Assuntos
Fertilidade , Hemípteros , Rickettsia , Razão de Masculinidade , Simbiose , Animais , Rickettsia/fisiologia , Hemípteros/microbiologia , Hemípteros/fisiologia , Feminino , Masculino , Hormônios Juvenis/metabolismo , China
2.
J Cancer ; 15(12): 4020-4039, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911387

RESUMO

Background: Matrix metalloproteinases (MMPs) are involved in many processes of tumour progression and invasion. However, few studies have analysed the effects of MMP expression patterns on endometrial cancer (EC) development from the perspective of the tumour microenvironment (TME). we quantified MMP expression in individual by constructing an MMP score and found MMP score effectively predict the prognosis of EC patients. Methods: MMPs expression profiles were determined based on the differential expression of 12 MMP-related regulators. Principal component analysis (PCA) was used to construct an MMP scoring system which can quantify the MMPs expression patterns individually of EC patients. Kaplan-Meier analysis, the log-rank test, and time-dependent receiver operating characteristic (ROC) curve analysis were used to evaluate the value of MMPs expression in predicting prognosis. Single-cell RNA sequencing (scRNA-seq) dataset was used to verify correlation between MMPs and progression of EC. Gene Ontology (GO) analysis was used to investigate the pathways and functions underlying MMPs expression. Tumour immune dysfunction, exclusion prediction, and pharmacotherapy response analyses were performed to assess the potential response to pharmacotherapy based on MMPs patterns. Results: We downloaded the MMPs expression data, somatic mutation data and corresponding clinical information of EC patients from the TCGA website and ICGC portal. Based on the MMP-related differentially expressed genes (DEGs), the MMP score was constructed, and EC patients were divided into high and low MMP score groups. There was a positive correlation between MMP score and prognosis of EC patients. Patients with high MMP scores had better prognosis, more abundant immune cell infiltration and stronger antitumoor immunity. Although prognosis is worse with the lower group than the high, patients with low MMP score had better response to immunotherapy, which means they could prolong the survival time through Immunological checkpoint blockade (ICB) therapy. scRNA-seq analysis identified significant heterogeneity between MMP score and classical pathways in EC. Conclusion: Our work indicates that the MMP score could be a potential tool to evaluate MMP expression patterns, immune cell infiltration, response to pharmacotherapy, clinicopathological features, and survival outcomes in EC. This will provide the more effective guide to select immunotherapeutic strategies of EC in the future.

3.
J Chem Theory Comput ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900275

RESUMO

Self-assembly of platinum(II) complex foldamers is an essential approach to fabricate advanced luminescent materials. However, a comprehensive understanding of folding kinetics and their absorption spectra remains elusive. By constructing Markov state models (MSMs) from large-scale molecular dynamics simulations, we reveal that two largely similar dinuclear alknylplatinum(II) terpyridine foldamers, Pt-PEG and Pt-PE with slightly different bridges, exhibit distinctive folding kinetics. Particularly, Pt-PEG bears bridge-dominant, plane-dominant, and cooperative pathways, while Pt-PE only prefers the plane-dominant pathway. Such preference originates from their difference in intrabridge electrostatic interactions, leading to contrastive distributions of metastable states. We also found that the bridge-dominant pathway for Pt-PEG becomes more favorable when lowering the temperature. Interestingly, based on the comprehensive conformation ensembles from our MSMs, we reveal the conformation-dependent absorption spectra of Pt-PEG and Pt-PE. Our theoretical spectra not only align with experimental results but also reveal the contributions of diverse conformations to the overall absorption bands explicitly, facilitating the rational design of stimuli-responsive smart luminescent molecules.

4.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2776-2782, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812178

RESUMO

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.


Assuntos
Antivirais , Dioscorea , Vírus da Hepatite B , Polissacarídeos , Proteínas Quinases p38 Ativadas por Mitógeno , Humanos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Polissacarídeos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Células Hep G2 , Antivirais/farmacologia , Dioscorea/química , Sinergismo Farmacológico , Nucleosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/metabolismo , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Guanina/análogos & derivados , Guanina/farmacologia
5.
Curr Biol ; 34(11): 2359-2372.e9, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38692276

RESUMO

Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.


Assuntos
Transferência Genética Horizontal , Simbiose , Vespas , Wolbachia , Animais , Wolbachia/fisiologia , Wolbachia/genética , Vespas/fisiologia , Vespas/microbiologia , Vespas/genética , Simbiose/genética , Feminino , Masculino , Partenogênese/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Processos de Determinação Sexual/genética
6.
J Agric Food Chem ; 72(19): 10970-10980, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38708787

RESUMO

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.


Assuntos
Alcaloides , Aspergillus fumigatus , Endófitos , Alcaloides/farmacologia , Alcaloides/química , Aspergillus fumigatus/efeitos dos fármacos , Endófitos/química , Estrutura Molecular , Fusarium/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Folhas de Planta/microbiologia , Folhas de Planta/química , Testes de Sensibilidade Microbiana , China , Doenças das Plantas/microbiologia
7.
Front Genet ; 15: 1359579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586585

RESUMO

Background: Systemic inflammatory regulators have been associated with preeclampsia (PE) during pregnancy; however, there is inconsistent evidence from animal models and observational results. Methods: Using summary data from genome-wide association studies (GWASs), we performed a bidirectional Mendelian randomization (MR) analysis of two samples of systemic inflammatory regulators (n = 8,186) and PE (n = 267,242) individuals of European ancestry. As our primary analysis, we used the random-effects inverse-variance weighted (IVW) approach. Sensitivity and pleiotropy analyses were conducted using the MR-Egger method, weighted median, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Cochran's Q test. Results: The results indicate that there is a correlation between a higher circulating level of tumor necrosis factor alpha (TNF-α) and interleukin-9 (IL-9) and an increased risk of PE (odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.09-1.60, p = 0.004 and OR = 1.28, 95% CI: 1.02-1.62, p = 0.033, respectively). Conversely, lower levels of stem cell growth factor beta (SCGF-ß) (OR = 0.89, 95% CI: 0.80-0.99, p = 0.027) and interleukin-5 (IL-5) (OR = 0.80, 95% CI: 0.65-0.98, p = 0.030) are linked to an increased risk of PE. The macrophage migration inhibitory factor (MIF) is the downstream inflammatory regulator of PE, according to reverse magnetic resonance imaging studies. Conclusion: Our study suggests that SCGF-ß, IL-5, IL-9, and TNF-α causally affect the PE risk, while PE is causally associated with MIF. Further studies are needed to validate these biomarkers in managing PE.

8.
Tissue Cell ; 88: 102347, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489914

RESUMO

BACKGROUND/PURPOSE: Nano-hydroxyapatite (nHA)/ gel porous scaffolds loaded with WSM carriers are promising bone replacement materials that can improve osseointegration ability. This investigation aimed to evaluate the osteoinductive activity by implanting the composition of nano-hydroxyapatite (nHA)/ Gel porous scaffolds as a carrier of WSM via an animal model. MATERIALS AND METHODS: WSM was extracted and nHA was added to the matrix to construct porous composite scaffolds. The dose-effect curve of WSM concentration and alkaline phosphatase (ALP) activity was made by culturing rat osteoblasts and examining the absorbance. Three different materials were implanted into critical size defects (CSD) in the skulls of rats, which were further divided into four groups: WSM nHA /Gel group, n-WSM nHA /Gel group, HA powder group, and control group. RESULTS: WSM (150 µg/mL-250µg/mL) effectively improved the activity of ALP in rat osteoblasts. All rats in each group had normal healing. WSM-loaded nHA /Gel group showed better performance on newly-formed bone tissue of rat skull and back at 4th week and 8th week, respectively. At the 4th week, the network of woven bone formed in the WSM-loaded nHA/Gel scaffold material. At 8th week, the reticular trabecular bone in the WSM-loaded scaffold material became dense lamellar bone, and the defect was mature lamellar bone. In the subcutaneous implantation experiment, WSM-loaded nHA/Gel scaffold material showed a better performance of heterotopic ossification than the pure nHA/Gel scaffold material. CONCLUSION: WSM promotes osteoblast differentiation and bone mineralization. The results confirm that the nHA/ Gel Porous Scaffold with Nacre Water-Soluble Matrix has a significant bone promoting effect and can be used as a choice for tissue engineering to repair bone defects.


Assuntos
Durapatita , Osteoblastos , Osteogênese , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Osteogênese/efeitos dos fármacos , Durapatita/química , Durapatita/farmacologia , Ratos , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Porosidade , Masculino , Fosfatase Alcalina/metabolismo , Géis/química , Ratos Sprague-Dawley , Água/química , Crânio
9.
Behav Brain Res ; 466: 114974, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38554850

RESUMO

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.


Assuntos
Região CA1 Hipocampal , Dendritos , Diterpenos do Tipo Caurano , Potenciação de Longa Duração , Animais , Feminino , Masculino , Região CA1 Hipocampal/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Camundongos , Dendritos/efeitos dos fármacos , Memória/efeitos dos fármacos , Fatores Sexuais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia
10.
Medicine (Baltimore) ; 103(13): e37660, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552047

RESUMO

To explore the antiinflammatory mechanism of agarwood on recurrent aphthous stomatitis (RAS). RAS is the most common mucosal disease in the oral cavity. The clinical application of traditional Chinese medicine found that agarwood has significant curative effect on peptic ulcer, but the effect and mechanism of agarwood on RAS remain unclear. This study is intended to predict the potential antiinflammatory mechanisms by which agarwood acts on RAS through network pharmacology and molecular docking. TCMSP database was used to screen the active components of agarwood. RAS targets were screened in Genecards, DisGeNET, and OMIM database. Venny, an online tool, screens for interacting genes between the two. Cytoscape software was used to construct the gene regulation map of active compounds target of agarwood. String Database building protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were enriched in DAVID database. The key active ingredients and core targets were further verified by molecular docking. There were 9 effective compounds and 186 target genes in agarwood; RAS has 793 target genes. There were 41 interacting genes between agarwood and RAS. Interleukin 6, tumor necrosis factor, interleukin 1 beta, and cellular component motif ligand 2 may be key targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted multiple pathways associated with RAS. Molecular docking results showed that the active compounds of agarwood combined well and stably with the target. The Chinese herbal medicine agarwood can relieve the inflammation of RAS through multiple targets and various ways. Its active compounds may be nominated as candidates for antiinflammatory drugs of RAS.


Assuntos
Medicamentos de Ervas Chinesas , Estomatite Aftosa , Humanos , Estomatite Aftosa/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
11.
Mol Genet Metab Rep ; 38: 101048, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38469088

RESUMO

Background: Galactosemia was introduced into Taiwan's routine newborn screening (NBS) program in 1985. This study presents a 12-year experience, emphasizing disease diagnosis and screening performance. Method: NBS for galactosemia utilized dried blood spot samples taken 48-72 h post-delivery, with total galactose (TGal) level as the primary marker. Newborns with critical TGal levels were referred immediately, while those with borderline TGal underwent a recall test. GALT activity measurement was applied simultaneously as the second-tier marker. Further confirmatory tests, such as whole exome sequencing (WES), were conducted upon referral. Results: From January 1st, 2011, to December 31st, 2022, 51 cases were identified from 817,906 newborns. Of these, nine individuals had persistently elevated TGal. Diagnoses included one case of GALT deficiency, one of GALM deficiency, and seven of GALE deficiencies. Notably, the classic galactosemia patient (GALT deficiency) presented with extreme high TGal and was referred to the hospital for diet management immediately. All affected patients were instructed to adopt a galactose-restricted diet. By the median age of 2.5 years, all exhibited normal development and liver function. Conclusion: The incidence of classical galactosemia and its variants is extremely low in Taiwan. Incorporating WES into NBS has improved our ability to detect various galactosemia forms, enriching our understanding of the genetic underpinnings. While these newly discovered forms often present with milder initial elevations in TGal, specific biochemical investigations and regular monitoring are essential to understanding the long-term implications and outcomes.

12.
iScience ; 27(3): 109128, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38384835

RESUMO

Visual perceptual learning (VPL), experience-induced gains in discriminating visual features, has been studied extensively and intensively for many years, its profile in feature space, however, remains unclear. Here, human subjects were trained to perform either a simple low-level feature (grating orientation) or a complex high-level object (face view) discrimination task over a long-time course. During, immediately after, and one month after training, all results showed that in feature space VPL in grating orientation discrimination was a center-surround profile; VPL in face view discrimination, however, was a monotonic gradient profile. Importantly, these two profiles can be emerged by a deep convolutional neural network with a modified AlexNet consisted of 7 and 12 layers, respectively. Altogether, our study reveals for the first time a feature hierarchy-dependent profile of VPL in feature space, placing a necessary constraint on our understanding of the neural computation of VPL.

13.
World J Clin Cases ; 12(3): 657-664, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322452

RESUMO

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is an aggressive and rare variant of diffuse LBCL. Herein, we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar conjunctiva. CASE SUMMARY: A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months, accompanied by swelling and pain that had persisted for 3 d. Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye. Microscopically, the tumor was composed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells. Immunophenotypically, the neoplastic cells were positive for ALK, CD10, CD138, Kappa, MUM1, BOB.1, OCT-2, CD4, CD45, EMA, CD79a, CD38, and AE1/AE3, and negative for CD20, PAX5, Lambda, BCL6, CD30 and all other T-cell antigens. The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearrangements. Fluorescence in situ hybridization studies did not reveal any BCL2, BCL6 or MYC rearrangements. Furthermore, Epstein-Barr virus was not detected by in situ hybridization in the lesions. Based on the histopathological and imaging examinations, the neoplasm was classified as stage IE ALK-positive LBCL. No further treatments were administered. At the 6, 15, and 21 mo postoperative follow-up visits, the patient was in good condition, without obvious discomfort. This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass, which is extremely rare and shares morphological and immunohistochemical features with a variety of other neoplasms that can result in misdiagnosis. CONCLUSION: Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.

14.
Colloids Surf B Biointerfaces ; 234: 113746, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199187

RESUMO

Ischemic stroke is a neurological disease that leads to brain damage and severe cognitive impairment. In this study, extracellular vesicles(Ev) derived from mouse hippocampal cells (HT22) were used as carriers, and adenosine (Ad) was encapsulated to construct Ev-Ad to target the damaged hippocampus. The results showed that, Ev-Ad had significant antioxidant effect and inhibited apoptosis. In vivo, Ev-Ad reduced cell death and reversed inflammation in hippocampus of ischemic mice, and improved long-term memory and learning impairment by regulating the expression of the A1 receptor and the A2A receptor in the CA1 region. Thus, the developmental approach based on natural carriers that encapsulating Ad not only successfully restored nerves after ischemic stroke, but also improved cognitive impairment in the later stage of ischemic stroke convalescence. The development and design of therapeutic drugs provides a new concept and method for the treatment of cognitive impairment in the convalescent phase after ischemic stroke.


Assuntos
Vesículas Extracelulares , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Camundongos , Adenosina/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Hipocampo , Vesículas Extracelulares/metabolismo , Cognição , AVC Isquêmico/metabolismo
15.
Adv Mater ; 36(6): e2305384, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37672674

RESUMO

Adoptive cell therapy has emerged as a promising approach for cancer treatment. However, the transfer of macrophages exhibits limited efficacy against solid tumors due to the dynamic cellular phenotypic shift from antitumor to protumor states within the immunosuppressive tumor microenvironment. In this study, a strategy of attaching bacteria to macrophages (Mø@bac) is reported that endows adoptively infused macrophages with durable stimulation by leveraging the intrinsic immunogenicity of bacteria. These attached bacteria, referred to as backpacks, are encapsulated with adhesive nanocoatings and can sustainably control the cellular phenotypes in vivo. Moreover, Mø@bac can repolarize endogenous tumor-associated macrophages, leading to a more robust immune response and thus reducing the tumor progression in a murine 4T1 cancer model without any side effects. This study utilizing bacteria as cellular backpacks opens a new avenue for the development of cell therapies.


Assuntos
Neoplasias , Camundongos , Animais , Neoplasias/patologia , Macrófagos , Transferência Adotiva , Bactérias , Microambiente Tumoral , Imunoterapia
16.
Faraday Discuss ; 249(0): 181-194, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-37791622

RESUMO

The nanoconfinement of water can result in dramatic differences in its physical and chemical properties compared to bulk water. However, a detailed molecular-level understanding of these properties is still lacking. Vibrational spectroscopy, such as Raman and infrared, is a popular experimental tool for studying the structure and dynamics of water, and is often complemented by atomistic simulations to interpret experimental spectra, but there have been few theoretical spectroscopy studies of nanoconfined water using first-principles methods at ambient conditions, let alone under extreme pressure-temperature conditions. Here, we compute the Raman and IR spectra of water nanoconfined by graphene at ambient and extreme pressure-temperature conditions using ab initio simulations. Our results revealed alterations in the Raman stretching and low-frequency bands due to the graphene confinement. We also found spectroscopic evidence indicating that nanoconfinement considerably changes the tetrahedral hydrogen bond network, which is typically found in bulk water. Furthermore, we observed an unusual bending band in the Raman spectrum at ∼10 GPa and 1000 K, which is attributed to the unique molecular structure of confined ionic water. Additionally, we found that at ∼20 GPa and 1000 K, confined water transformed into a superionic fluid, making it challenging to identify the IR stretching band. Finally, we computed the ionic conductivity of confined water in the ionic and superionic phases. Our results highlight the efficacy of Raman and IR spectroscopy in studying the structure and dynamics of nanoconfined water in a large pressure-temperature range. Our predicted Raman and IR spectra can serve as a valuable guide for future experiments.

17.
Langmuir ; 40(1): 614-623, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38150370

RESUMO

Solar-energy-driven CO2 hydrogenation is a promising strategy to alleviate the climate crisis. Methane is a desirable derivative of CO2 reduction. However, developing a photocatalyst for highly active and selective CH4 generation remains challenging. Herein, we report a double Z-scheme Bi3O4Cl/g-C3N4/Cd0.5Zn0.5S photocatalyst for efficient reduction of CO2 to CH4. In situ characterization techniques confirmed that the charge migration mechanism in Bi3O4Cl/g-C3N4/Cd0.5Zn0.5S promotes charge separation through double internal electric fields. As a result, the optimized C0.01B0.02C catalyst displayed a formation rate high up to 25.34 µmol g-1 h-1 and a selectivity of 96.52% of CH4. Moreover, the AQY of CO2 conversion on C0.01B0.02C (1.84%) was almost 41 times higher than that of the bare CN. This study provides a novel perspective to develop heterojunction photocatalysts for selective CO2 conversion to CH4.

18.
ACS Nano ; 17(24): 24947-24960, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38055727

RESUMO

Cancer vaccines have been considered to be an alternative therapeutic strategy for tumor therapy in the past decade. However, the popularity and efficacy of cancer vaccines were hampered by tumor antigen heterogeneity and the impaired function of cross-presentation in the tumor-infiltrating dendritic cells (TIDCs). To overcome these challenges, we engineered an in situ nanovaccine (named as TPOP) based on lipid metabolism-regulating and innate immune-stimulated nanoparticles. TPOP could capture tumor antigens and induce specific recognition by TIDCs to be taken up. Meanwhile, TPOP could manipulate TIDC lipid metabolism and inhibit de novo synthesis of fatty acids, thus improving the ability of TIDCs to cross-present by reducing their lipid accumulation. Significantly, intratumoral injection of TPOP combined with pretreatment with doxorubicin showed a considerable therapeutic effect in the subcutaneous mouse colorectal cancer model and melanoma model. Moreover, in combination with immune checkpoint inhibitors, such TPOP could markedly inhibit the growth of distant tumors by systemic antitumor immune responses. This work provides a safe and promising strategy for improving the function of immune cells by manipulating their metabolism and activating the immune system effectively for in situ cancer vaccines.


Assuntos
Vacinas Anticâncer , Melanoma , Nanopartículas , Neoplasias , Camundongos , Animais , Nanovacinas , Células Dendríticas , Metabolismo dos Lipídeos , Imunoterapia , Neoplasias/tratamento farmacológico , Melanoma/tratamento farmacológico , Antígenos de Neoplasias/metabolismo , Modelos Animais de Doenças
19.
Curr Med Sci ; 43(6): 1075-1083, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38041791

RESUMO

Endometrial receptivity is an important factor that influences embryo implantation. Thus, it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology. Recently, growing evidence has indicated that intrauterine platelet-rich plasma (PRP) infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity. Therefore, the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.


Assuntos
Transferência Embrionária , Plasma Rico em Plaquetas , Humanos , Feminino , Implantação do Embrião , Endométrio , Técnicas de Reprodução Assistida
20.
Front Med (Lausanne) ; 10: 1259680, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38105903

RESUMO

Background: Cadmium (Cd) is a heavy metal associated with several human disorders. Preeclampsia is a major cause of maternal mortality worldwide. The association between maternal Cd exposure and preeclampsia remains elusive. Methods: To better understand this relationship, we conducted a systematic review and meta-analysis of eligible studies from five databases (PubMed, Embase, Web of Science, Scopus, and CNKI) from their inception to September 10, 2022. The quality of these studies was evaluated using the Newcastle-Ottawa quality assessment scale (NOS). We use random-effects models to calculate overall standardized mean differences (SMDs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to assess the robustness of our results. We also evaluated publication bias using Egger's and Begg's tests. Additionally, we conducted meta-regression and sub-group analyses to identify potential sources of heterogeneity between studies. Results: Our analysis included a total of 17 studies with 10,373 participants. We found a significant association between maternal cadmium exposure and the risk of preeclampsia (SMD 0.27, 95% CI 0.09-0.44, p < 0.01). No significant publication bias was detected in Begg's or Egger's tests. Meta-regression suggested that geographical location, year of publication, cadmium samples, sample size, and measurement methods did not contribute to heterogeneity between studies. Conclusion: Our findings suggest that maternal blood cadmium levels are associated with an increased risk of preeclampsia. In contrast, the pregnant women's urine or placental levels of cadmium may not suggest preeclamptic risk during pregnancy. Further high-quality clinical studies and animal experiments are needed to understand this association better. Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=361291, identifier: CRD42022361291.

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