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1.
Biomater Sci ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979695

RESUMO

Objective: To conduct bibliometric analysis of the application of inorganic nanomaterials to autoimmune diseases to characterize current research trends and to visualize past and emerging trends in this field in the past 15 years. Methods: The evolution and thematic trends of the application of inorganic nanomaterials to autoimmune diseases from January 1, 1985, to March 15, 2024, were analyzed by bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database. A total of 734 relevant reports in the literature were evaluated according to specific characteristics such as year of publication, journal, institution, country/region, references, and keywords. VOSviewer was used to build co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization. Some important subtopics identified by bibliometric characterization are further discussed and reviewed. Result: From 2009 to 2024, annual publications worldwide increased from 11 to 95, an increase of 764%. ACS Nano published the most papers (14) with the most citations (1372). China (230 papers, 4922 citations) and the Chinese Academy of Sciences (36 papers, 718 citations) are the most productive and influential country and institution, respectively. The first 100 keywords were co-clustered to form four clusters: (1) the application of inorganic nanomaterials in drug delivery, (2) the application of inorganic nano-biosensing to autoimmune diseases, (3) the use of inorganic nanomaterials for imaging applied to autoimmune diseases, and (4) the application of inorganic nanomaterials in the treatment of autoimmune diseases. Combination therapy, microvesicles, photothermal therapy (PTT), targeting, diagnostics, transdermal, microneedling, silver nanoparticles, psoriasis, and inflammatory cytokines are the latest high-frequency keywords, marking the emerging frontier of inorganic nanomaterials in the field of autoimmune diseases. Sub-topics were further discussed to help researchers determine the scope of research topics and plan research directions. Conclusion: Over the past 39 years, the application of inorganic nanotechnology to the field of autoimmune diseases shows extensive cooperation between countries and institutions, showing a continuous increase in the number of reports in the literature, and has clinical translation prospects. Future research should further improve the safety of inorganic nanomaterials, clarify the mechanism of action of nanomaterials, establish a standardized nanomaterial preparation and performance evaluation system, and ultimately achieve the goal of early detection and precise treatment of autoimmune diseases.

2.
J Integr Plant Biol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980229

RESUMO

Prime editing is a versatile CRISPR/Cas-based precise genome-editing technique for crop breeding. Four new types of prime editors (PEs) named PE6a-d were recently generated using evolved and engineered reverse transcriptase (RT) variants from three different sources. In this study, we tested the editing efficiencies of four PE6 variants and two additional PE6 constructs with double-RT modules in transgenic rice (Oryza sativa) plants. PE6c, with an evolved and engineered RT variant from the yeast Tf1 retrotransposon, yielded the highest prime-editing efficiency. The average fold change in the editing efficiency of PE6c compared with PEmax exceeded 3.5 across 18 agronomically important target sites from 15 genes. We also demonstrated the feasibility of using two RT modules to improve prime-editing efficiency. Our results suggest that PE6c or its derivatives would be an excellent choice for prime editing in monocot plants. In addition, our findings have laid a foundation for prime-editing-based breeding of rice varieties with enhanced agronomically important traits.

3.
aBIOTECH ; 5(2): 117-126, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38978783

RESUMO

Cas12a (Cpf1), a Class 2 Type V CRISPR/Cas nuclease, has several unique attributes for genome editing and may provide a valuable alternative to Cas9. However, a low editing efficiency due to temperature sensitivity and insufficient cleavage activity of the Cas12a nuclease are major obstacles to its broad application. In this report, we generated two variants, ttAsCas12 Ultra and ttLbCas12a Ultra harboring three (E174R, M537R, and F870L) or two (D156R and E795L) mutations, respectively, by combining the mutations from the temperature-tolerant variants ttAsCas12a (E174R) and ttLbCas12a (D156R), and those from the highly active variants AsCas12a Ultra (M537R and F870L) and LbCas12a Ultra (E795L). We compared editing efficiencies of the five resulting Cas12a variants (LbCas12a, ttLbCas12a, ttLbCas12a Ultra, AsCas12a Ultra, and ttAsCas12 Ultra) at six target sites of four genes in Arabidopsis (Arabidopsis thaliana). The variant ttLbCas12a Ultra, harboring the D156R and E795L mutations, exhibited the highest editing efficiency of all variants tested in Arabidopsis and can be used to generate homozygous or biallelic mutants in a single generation in Arabidopsis plants grown at 22 °C. In addition, optimization of ttLbCas12a Ultra, by varying nuclear localization signal sequences and codon usage, further greatly improved editing efficiency. Collectively, our results indicate that ttLbCas12a Ultra is a valuable alternative to Cas9 for editing genes or promoters in Arabidopsis. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00144-w.

4.
Elife ; 132024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949652

RESUMO

Tubulin posttranslational modifications (PTMs) modulate the dynamic properties of microtubules and their interactions with other proteins. However, the effects of tubulin PTMs were often revealed indirectly through the deletion of modifying enzymes or the overexpression of tubulin mutants. In this study, we directly edited the endogenous tubulin loci to install PTM-mimicking or -disabling mutations and studied their effects on microtubule stability, neurite outgrowth, axonal regeneration, cargo transport, and sensory functions in the touch receptor neurons of Caenorhabditis elegans. We found that the status of ß-tubulin S172 phosphorylation and K252 acetylation strongly affected microtubule dynamics, neurite growth, and regeneration, whereas α-tubulin K40 acetylation had little influence. Polyglutamylation and detyrosination in the tubulin C-terminal tail had more subtle effects on microtubule stability likely by modulating the interaction with kinesin-13. Overall, our study systematically assessed and compared several tubulin PTMs for their impacts on neuronal differentiation and regeneration and established an in vivo platform to test the function of tubulin PTMs in neurons.


Assuntos
Caenorhabditis elegans , Microtúbulos , Processamento de Proteína Pós-Traducional , Tubulina (Proteína) , Animais , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Microtúbulos/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Acetilação , Axônios/metabolismo , Axônios/fisiologia , Fosforilação , Regeneração Nervosa , Cinesinas/metabolismo , Cinesinas/genética
5.
Biomed Pharmacother ; 177: 117134, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39013225

RESUMO

Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy. In this study, we describe a previously unreported potentiating effect of Icariside I (ICA I, GH01), the main bioactive compound isolated from the Epimedium species, on anti-tumor immune responses. Mechanistically, molecular docking and SPR assay result show that ICA I binding with TRPV4. ICA I induced intracellular Ca2+ increasing and mitochondrial DNA release by targeting TRPV4, which triggered cytosolic ox-mitoDNA release. Importantly, these intracellular ox-mitoDNA fragments were taken up by immune cells in the tumor microenvironment, which amplified the immune response. Moreover, our study shows the remarkable efficacy of sequential administration of ICA I and anti-α-PD-1 mAb in advanced tumors and provides a strong scientific rationale for recommending such a combination therapy for clinical trials. ICA I enhanced the anti-tumor effects with PD-1 inhibitors by regulating the TRPV4/Ca2+/Ox-mitoDNA/cGAS/STING axis. We expect that these findings will be translated into clinical therapies, which will benefit more patients with cancer in the near future.

6.
Adv Healthc Mater ; : e2401600, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011808

RESUMO

The prevalence of retinal neovascular diseases necessitates novel treatments beyond current therapies like laser surgery or anti-VEGF treatments, which often carry significant side effects. A novel therapeutic approach is introduced using copper-containing layered double hydroxides (Cu-LDH) nanozymes integrated with nitric oxide-releasing molecules (GSHNO), forming Cu-LDH@GSHNO aimed at combating oxidative stress within the retinal vascular system. Combination of synthetic chemistry and biological testing, Cu-LDH@GSHNO are synthesized, characterized, and assessed for curative effect in HUVECs and an oxygen-induced retinopathy (OIR) mouse model. The results indicate that Cu-LDH@GSHNO demonstrates SOD-CAT cascade catalytic ability, accompanied with GSH and nitric oxide-releasing capabilities, which significantly reduces oxidative cell damage and restores vascular function, presenting a dual-function strategy that enhances treatment efficacy and safety for retinal vascular diseases. The findings encourage further development and clinical exploration of nanozyme-based therapies, promising a new horizon in therapeutic approaches for managing retinal diseases driven by oxidative stress.

7.
mSphere ; : e0025424, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046230

RESUMO

Tuberculosis (TB) remains one of the infectious diseases with high incidence and high mortality. About a quarter of the population has been latently infected with Mycobacterium tuberculosis. At present, the available TB treatment strategies have the disadvantages of too long treatment duration and serious adverse reactions. The sustained inflammatory response leads to permanent tissue damage. Unfortunately, the current selection of treatment regimens does not consider the immunomodulatory effects of various drugs. In this study, we preliminarily evaluated the effects of commonly used anti-tuberculosis drugs on innate immunity at the cellular level. The results showed that clofazimine (CFZ) has a significant innate immunosuppressive effect. CFZ significantly inhibited cytokines and type I interferons (IFNα and IFNß) expression under both lipopolysaccharide stimulation and CFZ-resistant strain infection. In further mechanistic studies, CFZ strongly inhibited the phosphorylation of nuclear factor kappa B (NF-κB) p65 and had no significant effect on the phosphorylation of p38. In conclusion, our study found that CFZ suppresses innate immunity against Mycobacterium tuberculosis by NF-κB, which should be considered in future regimen development. IMPORTANCE: The complete elimination of Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, from TB patients is a complicated process that takes a long time. The excessive immune inflammatory response of the host for a long time causes irreversible organic damage to the lungs and liver. Current antibiotic-based treatment options involve multiple complex drug combinations, often targeting different physiological processes of Mtb. Given the high incidence of post-tuberculosis lung disease, we should also consider the immunomodulatory properties of other drugs when selecting drug combinations.

8.
Anal Biochem ; : 115625, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39038508

RESUMO

As the main active glycoprotein of egg white, the biological functions of chicken ovomucin α- and ß-subunit are closely related to the structure of glycans. However, the exact composition and structure of the subunit glycans are still unknown. We obtained highly pure chicken ovomucin α-subunit and ß-subunit protein bands by the strategy combined with two-step isoelectric precipitation and SDS-PAGE gel electrophoresis. The ammonia-catalyzed one-pot procedure was then used to release and capture α-and ß-subunit protein glycans with 1-phenyl- 3-Methyl-5-pyrazolone (PMP). The N/O-glycans of bis-PMP derivatives were purified and analyzed by LC-MS. More importantly, an effective dual modification was performed to accurately quantify neutral and sialylated O-glycans through methylamidation of sialic acid residues and simultaneously through carbonyl condensation reactions of reducing ends with PMP. We first showed that the α-subunit protein has only N-glycosylation modification, and the ß-subunit only O-glycosylation, a total of 22 N-glycans and 20 O-glycans were identified in the α- and ß-subunit, respectively. In addition, the complex N-glycan (47%) and the sialylated O-glycan (77%) are each major types of the above subunits. Such findings in this study provide a basis for studying the functional and biological activities of chicken ovomucin glycans.

9.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3263-3269, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39041088

RESUMO

Numerous studies show that Lonicera macranthoides and L. japonica have significant differences in organic matter. However, there is still a lack of research on inorganic elements between them. In this study, a non-targeted elemental metabolomics method was established by inductively coupled plasma mass spectrometry(ICP-MS), so as to compare the overall differences of inorganic elements between L. macranthoides and L. japonica. In addition, the differential markers were screened, and these differential markers were quantitatively analyzed by the targeted method. The non-targeted elemental metabolomics showed that the established mathematical model could reflect the difference in element content between L. macranthoides and L. japonica. Four inorganic elements such as ~(55)Mn, ~(209)Bi, ~(111)Cd, and ~(85)Rb were confirmed as the differential markers of L. macranthoides and L. japonica based on the screening principles of variable importance in the projection(VIP) value>2.0, P<0.01 and fold change(FC) value>1.2 or <0.80. The targeted quantitative results showed that the content of ~(209)Bi in L. japonica was significantly higher than that in L. macranthoides, while ~(55)Mn, ~(111)Cd, and ~(85)Rb in L. macranthoides were significantly higher than that in L. japonica. The non-targeted and targeted elemental metabolomics methods based on ICP-MS can significantly reflect the overall differences in inorganic elements between L. macranthoides and L. japonica. Exploring the differences between them from the perspective of elements can partly reflect the differences in their drug properties and lay a foundation for further study on the quality control mode of inorganic elements in L. macranthoides and L. japonica and their pharmacological effects.


Assuntos
Lonicera , Espectrometria de Massas , Metabolômica , Controle de Qualidade , Lonicera/química , Espectrometria de Massas/métodos , Metabolômica/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise
10.
J Am Chem Soc ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042557

RESUMO

Achieving high guest loading and multiguest-binding capacity holds crucial significance for advancement in separation, catalysis, and drug delivery with synthetic receptors; however, it remains a challenging bottleneck in characterization of high-stoichiometry guest-binding events. Herein, we describe a large-sized coordination cage (MOC-70-Zn8Pd6) possessing 12 peripheral pockets capable of accommodating multiple guests and a high-resolution electrospray ionization mass spectrometry (HR-ESI-MS)-based method to understand the solution host-guest chemistry. A diverse range of bulky guests, varying from drug molecules to rigid fullerenes as well as flexible host molecules of crown ethers and calixarenes, could be loaded into open pockets with high capacities. Notably, these hollow cage pockets provide multisites to capture different guests, showing heteroguest coloading behavior to capture binary, ternary, or even quaternary guests. Moreover, a pair of commercially applied drugs for the combination therapy of chronic lymphocytic leukemia (CLL) has been tested, highlighting its potential in multidrug delivery for combined treatment.

11.
Vet Microbiol ; 296: 110173, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38971119

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant disease caused by porcine reproductive and respiratory syndrome virus (PRRSV). Type I interferon (IFN) induces a large number of interferon-stimulated genes (ISGs) expression to inhibit PRRSV infection. To survive in the host, PRRSV has evolved multiple strategies to antagonize host innate immune response. Previous studies have reported that PRRSV N protein decreases the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress IFN-ß production. However, whether other PRRSV proteins inhibit the antiviral function of TRIM25 is less well understood. In this study, we first found that PRRSV NSP1α decreased ISGylation of TRIM25. Meanwhile, NSP1α significantly suppressed TRIM25-mediated IFN-ß production to promote PRRSV replication. Further studies demonstrated that PRRSV NSP1α reduced the protein level of TRIM25 in proteasome system but did not regulate the transcription level of TRIM25. In addition, the function of NSP1α in TRIM25 degradation did not rely on its papain-like cysteine protease activity. Taken together, PRRSV NSP1α antagonizes the antiviral response of TRIM25 by mediating TRIM25 degradation to promote PRRSV replication. Our data identify TRIM25 as a natural target of PRRSV NSP1α and reveal a novel mechanism that PRRSV induces TRIM25 degradation and inhibits host antiviral immune response.

12.
J Med Chem ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987863

RESUMO

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5 showed high affinity toward hTERT G4 (Kd = 1.1 µM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50 = 1 µM). In cell-based assays, 5 not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivo antitumor efficacy of 5 was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.

13.
Sci Rep ; 14(1): 16455, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014184

RESUMO

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.


Assuntos
Imagem de Tensor de Difusão , Humanos , Masculino , Recém-Nascido , Feminino , Imagem de Tensor de Difusão/métodos , Estudos Prospectivos , Hemorragia Cerebral/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/etiologia , Lactente , Hemorragia Cerebral Intraventricular/diagnóstico por imagem , Idade Gestacional , Desenvolvimento Infantil , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia
14.
Comput Biol Med ; 179: 108843, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39029433

RESUMO

Respiratory diseases are one of the major health problems worldwide. Early diagnosis of the disease types is of vital importance. As one of the main symptoms of many respiratory diseases, cough may contain information about different pathological changes in the respiratory system. Therefore, many researchers have used cough sounds to diagnose different diseases through artificial intelligence in recent years. The acoustic features and data augmentation methods commonly used in speech tasks are used to achieve better performance. Although these methods are applicable, previous studies have not considered the characteristics of cough sound signals. In this paper, we designed a cough-based respiratory disease classification system and proposed audio characteristic-dependent feature extraction and data augmentation methods. Firstly, according to the short durations and rapid transition of different cough stages, we proposed maximum overlapping mel-spectrogram to avoid missing inter-frame information caused by traditional framing methods. Secondly, we applied various data augmentation methods to mitigate the problem of limited labeled data. Based on the frequency energy distributions of different diseased cough audios, we proposed a parameter-independent self-energy-based augmentation method to enhance the differences between different frequency bands. Finally, in the model testing stage, we leveraged test-time augmentation to further improve the classification performance by fusing the test results of the original and multiple augmented audios. The proposed methods were validated on the Coswara dataset through stratified four-fold cross-validation. Compared to the baseline model using mel-spectrogram as input, the proposed methods achieved an average absolute performance improvement of 3.33% and 3.10% in macro Area Under the Receiver Operating Characteristic (macro AUC) and Unweighted Average Recall (UAR), respectively. The visualization results through Gradient-weighted Class Activation Mapping (Grad-CAM) showed the contributions of different features to model decisions.

15.
ACS Nano ; 18(28): 18712-18728, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38952208

RESUMO

Immunotherapy can potentially suppress the highly aggressive glioblastoma (GBM) by promoting T lymphocyte infiltration. Nevertheless, the immune privilege phenomenon, coupled with the generally low immunogenicity of vaccines, frequently hampers the presence of lymphocytes within brain tumors, particularly in brain tumors. In this study, the membrane-disrupted polymer-wrapped CuS nanoflakes that can penetrate delivery to deep brain tumors via releasing the cell-cell interactions, facilitating the near-infrared II (NIR II) photothermal therapy, and detaining dendritic cells for a self-cascading immunotherapy are developed. By convection-enhanced delivery, membrane-disrupted amphiphilic polymer micelles (poly(methoxypoly(ethylene glycol)-benzoic imine-octadecane, mPEG-b-C18) with CuS nanoflakes enhances tumor permeability and resides in deep brain tumors. Under low-power NIR II irradiation (0.8 W/cm2), the intense heat generated by well-distributed CuS nanoflakes actuates the thermolytic efficacy, facilitating cell apoptosis and the subsequent antigen release. Then, the positively charged polymer after hydrolysis of the benzoic-imine bond serves as an antigen depot, detaining autologous tumor-associated antigens and presenting them to dendritic cells, ensuring sustained immune stimulation. This self-cascading penetrative immunotherapy amplifies the immune response to postoperative brain tumors but also enhances survival outcomes through effective brain immunotherapy.


Assuntos
Neoplasias Encefálicas , Membrana Celular , Células Dendríticas , Imunoterapia , Raios Infravermelhos , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Animais , Camundongos , Humanos , Membrana Celular/química , Linhagem Celular Tumoral , Micelas , Nanopartículas/química , Terapia Fototérmica , Polietilenoglicóis/química , Glioblastoma/terapia , Glioblastoma/imunologia , Glioblastoma/patologia , Apoptose/efeitos dos fármacos
16.
Phytomedicine ; 132: 155854, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39032276

RESUMO

BACKGROUND: Recent investigations underscore the capacity of photodynamic therapy (PDT) to induce adipocyte apoptosis, thereby mitigating obesity. Nonetheless, extant synthetic photosensitizers manifest limitations that hinder their clinical viability. PURPOSE: In the current study, we used Hypericum perforatum-derived exosomes-like nanovesicles (HPExos) as a novel photosensitizer, and investigated its PDT effects in adipose tissue during obesity. METHOD: HPExos-were administered to high fat diet mice via intraperitoneal injection, followed by targeted irradiation with specialized LED lights. Mass spectrometric analysis was analyzed in adipose tissues. CCK8 assay and Oil Red O staining were used to investigate lipid accumulation in 3T3-L1 cells to clarify adipocyte differentiation. The expression levels of related markers associated with adipogenesis and lipogenesis were assessed by RT-PCR. Apoptosis analysis was performed by TUNEL staining of and western blotting. RESULTS: HPExos combined with PDT accumulated in visceral white adipose tissues results in a reduced body weight and improved insulin sensitivity. HPExos combined with PDT induced apoptosis by driving high levels of ROS. In addition, HPExos combined with PDT significantly downregulated the expression of transcription factors, PPARγ, C/EBPα, and SREBP and lipogenesis protein FABP4 both in vitro and in vivo, associated with a decreased FFA levels. CONCLUSION: These findings suggest that HPExos could act as an effective photosensitizer in regulating glucose hemostasis by inhibiting adipocyte differentiation and lipogenesis, offering a promising approach for obesity treatment.

17.
J Am Chem Soc ; 146(29): 20414-20424, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38982611

RESUMO

The structural dynamics of artificial assemblies, in aspects such as molecular recognition and structural transformation, provide us with a blueprint to achieve bioinspired applications. Here, we describe the assembly of redox-switchable chiral metal-organic cages Λ8/Δ8-[Pd6(CoIIL3)8]28+ and Λ8/Δ8-[Pd6(CoIIIL3)8]36+. These isomeric cages demonstrate an on-off chirality logic gate controlled by their chemical and stereostructural dynamics tunable through redox transitions between the labile CoII-state and static CoIII-state with a distinct Cotton effect. The transition between different states is enabled by a reversible redox process and chiral recognition originating in the tris-chelate Co-centers. All cages in two states are thoroughly characterized by NMR, ESI-MS, CV, CD, and X-ray crystallographic analysis, which clarify their redox-switching behaviors upon chemical reduction/oxidation. The stereochemical lability of the CoII-center endows the Λ8/Δ8-CoII-cages with efficient chiral-induction by enantiomeric guests, leading to enantiomeric isomerization to switch between Λ8/Δ8-CoII-cages, which can be stabilized by oxidation to their chemically inert forms of Λ8/Δ8-CoIII-cages. Kinetic studies reveal that the isomerization rate of the Δ8-CoIII-cage is at least an order of magnitude slower than that of the Δ8-CoII-cage even at an elevated temperature, while its activation energy is 16 kcal mol-1 higher than that of the CoII-cage.

18.
Heliyon ; 10(13): e33437, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040373

RESUMO

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018-December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

19.
J Clin Nurs ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886989

RESUMO

AIMS AND OBJECTIVES: To investigate the psychological distress, sexual satisfaction, and quality of life of gynaecological cancer survivors and their spouses during cancer survivorship. BACKGROUND: The survival rate of patients with cancer is increasing owing to advances in medical treatment technology. Spouses are the closest companions of gynaecological cancer survivors. Patients with gynaecological cancer and their spouses face different situations and challenges after experiencing cancer invasion. DESIGN: Questionnaire-based cross-sectional study. METHODS: Convenience sampling was employed, and 180 participants, including patients with gynaecological cancer and their spouses, were enrolled. A structured questionnaire was used to investigate the psychological distress, sexual satisfaction, and quality of life of gynaecological cancer survivors and their spouses during acute, extended, and permanent survivorship. The STROBE checklist guided the study preparation. RESULTS: For gynaecological cancer survivors and their spouses, (1) severe psychological distress was present during acute survivorship, with anxiety extending until permanent survivorship; (2) no significant differences were observed in pre- and post-treatment sexual satisfaction, although pre-treatment sexual satisfaction was higher than post-treatment sexual satisfaction in all three cancer survivorship stages and (3) quality of life decreased during acute survivorship and gradually improved with time. CONCLUSIONS: Psychological distress, sexual satisfaction and quality of life of gynaecological cancer survivors and their spouses worsened during acute survivorship and improved over time until permanent survivorship. RELEVANCE TO CLINICAL PRACTICE: Gynaecological cancer survivors and their spouses experience anxiety and depression from diagnosis confirmation until permanent survivorship (>5 years survival). Therefore, clinical nurses' sensitivity to emotional distress in cancer survivors and their spouses can be improved and a consistent and routine evaluation method has been established for the early detection of such emotional distress. The results of this study can provide a reference for clinical healthcare professionals and contribute to a better quality of care.

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