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1.
Plant Physiol ; 194(2): 787-804, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37815230

RESUMO

Root development influences plant responses to environmental conditions, and well-developed rooting enhances plant survival under abiotic stress. However, the molecular and genetic mechanisms underlying root development and abiotic stress tolerance in plants remain unclear. In this study, we identified the MYB transcription factor-encoding gene IbMYB73 by cDNA-amplified fragment length polymorphism and RNA-seq analyses. IbMYB73 expression was greatly suppressed under abiotic stress in the roots of the salt-tolerant sweet potato (Ipomoea batatas) line ND98, and its promoter activity in roots was significantly reduced by abscisic acid (ABA), NaCl, and mannitol treatments. Overexpression of IbMYB73 significantly inhibited adventitious root growth and abiotic stress tolerance, whereas IbMYB73-RNAi plants displayed the opposite pattern. IbMYB73 influenced the transcription of genes involved in the ABA pathway. Furthermore, IbMYB73 formed homodimers and activated the transcription of ABA-responsive protein IbGER5 by binding to an MYB binding sites I motif in its promoter. IbGER5 overexpression significantly inhibited adventitious root growth and abiotic stress tolerance concomitantly with a reduction in ABA content, while IbGER5-RNAi plants showed the opposite effect. Collectively, our results demonstrated that the IbMYB73-IbGER5 module regulates ABA-dependent adventitious root growth and abiotic stress tolerance in sweet potato, which provides candidate genes for the development of elite crop varieties with well-developed root-mediated abiotic stress tolerance.


Assuntos
Ácido Abscísico , Ipomoea batatas , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estresse Fisiológico/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Nano Lett ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606881

RESUMO

Photocatalysis offers a direct, yet robust, approach to eradicate pathogenic bacteria. However, the practical implementation of photocatalytic disinfection faces a significant challenge due to low-efficiency photogenerated carrier separation and transfer. Here, we present an effective approach to improve photocatalytic disinfection performance by exploiting the pyro-phototronic effect through a synergistic combination of pyroelectric properties and photocatalytic processes. A set of comprehensive studies reveals that the temperature fluctuation-induced pyroelectric field promotes photoexcited carrier separation and transfer and thus facilitates the generation of reactive oxygen species and ultimately enhances photocatalytic disinfection performance. It is worth highlighting that the constructed film demonstrated an exceptional antibacterial efficiency exceeding 95% against pathogenic bacteria under temperature fluctuations and light irradiation. Moreover, the versatile modulation role of the pyro-phototronic effect in boosting photocatalytic disinfection was corroborated. This work paves the way for improving photocatalytic disinfection efficiency by harnessing the synergistic potential of various inherent material properties.

3.
Small ; : e2400927, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726949

RESUMO

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

4.
Plant Physiol ; 191(1): 496-514, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36377782

RESUMO

Plant flavonoids are valuable natural antioxidants. Sweet potato (Ipomoea batatas) leaves are rich in flavonoids, regenerate rapidly, and can adapt to harsh environments, making them an ideal material for flavonoid biofortification. Here, we demonstrate that the B-box (BBX) family transcription factor IbBBX29 regulates the flavonoid contents and development of sweet potato leaves. IbBBX29 was highly expressed in sweet potato leaves and significantly induced by auxin (IAA). Overexpression of IbBBX29 contributed to a 21.37%-70.94% increase in leaf biomass, a 12.08%-21.85% increase in IAA levels, and a 31.33%-63.03% increase in flavonoid accumulation in sweet potato, whereas silencing this gene produced opposite effects. Heterologous expression of IbBBX29 in Arabidopsis (Arabidopsis thaliana) led to a dwarfed phenotype, along with enhanced IAA and flavonoid accumulation. RNA-seq analysis revealed that IbBBX29 modulates the expression of genes involved in the IAA signaling and flavonoid biosynthesis pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay indicated that IbBBX29 targets key genes of IAA signaling and flavonoid biosynthesis to activate their expression by binding to specific T/G-boxes in their promoters, especially those adjacent to the transcription start site. Moreover, IbBBX29 physically interacted with developmental and phenylpropanoid biosynthesis-related proteins, such as AGAMOUS-LIKE 21 protein IbAGL21 and MYB308-like protein IbMYB308L. Finally, overexpressing IbBBX29 also increased flavonoid contents in sweet potato storage roots. These findings indicate that IbBBX29 plays a pivotal role in regulating IAA-mediated leaf development and flavonoid biosynthesis in sweet potato and Arabidopsis, providing a candidate gene for flavonoid biofortification in plants.


Assuntos
Arabidopsis , Ipomoea batatas , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Flavonoides/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas
5.
J Environ Sci (China) ; 146: 176-185, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38969446

RESUMO

Microplastics (MPs) are commonly found with hydrophobic contaminants in the water column and pose a serious threat to aquatic organisms. The effects of polystyrene microplastics of different particle sizes on the accumulation of triclosan in the gut of Xenopus tropicalis, its toxic effects, and the transmission of resistance genes were evaluated. The results showed that co-exposure to polystyrene (PS-MPs) adsorbed with triclosan (TCS) caused the accumulation of triclosan in the intestine with the following accumulation capacity: TCS + 5 µm PS group > TCS group > TCS + 20 µm PS group > TCS + 0.1 µm PS group. All experimental groups showed increased intestinal inflammation and antioxidant enzyme activity after 28 days of exposure to PS-MPs and TCS of different particle sizes. The TCS + 20 µm PS group exhibited the highest upregulated expression of pro-inflammatory factors (IL-10, IL-1ß). The TCS + 20 µm group showed the highest increase in enzyme activity compared to the control group. PS-MPs and TCS, either alone or together, altered the composition of the intestinal microbial community. In addition, the presence of more antibiotic resistance genes than triclosan resistance genes significantly increased the expression of tetracycline resistance and sulfonamide resistance genes, which may be associated with the development of intestinal inflammation and oxidative stress. This study refines the aquatic ecotoxicity assessment of TCS adsorbed by MPs and provides informative information for the management and control of microplastics and non-antibiotic bacterial inhibitors.


Assuntos
Microplásticos , Tamanho da Partícula , Poliestirenos , Triclosan , Poluentes Químicos da Água , Xenopus , Animais , Triclosan/toxicidade , Poliestirenos/toxicidade , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Intestinos/efeitos dos fármacos , Adsorção , Expressão Gênica/efeitos dos fármacos
6.
Phys Chem Chem Phys ; 25(35): 23954-23962, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37642559

RESUMO

A broken-gap heterojunction is a bright approach for designing tunneling field-effect transistors (TFETs) due to its distinct quantum tunneling mechanisms. In this study, we investigate the electronic structure and transport characteristics of a SiC/Ti2CO2 heterojunction, as well as the impacts of electric field and strain on the electronic properties via density functional theory. We determine that the interfacial atoms of the heterojunction are covalently bonded, forming a type-III heterojunction with a broken-gap. There exists band-to-band tunneling (BTBT) from the valence band (VB) of SiC to the conduction band (CB) of Ti2CO2. The creation of the heterojunction also enhances the carrier mobility arising from the large elastic modulus and the decrease of deformation potential. The current-voltage (I-V) characteristics of the device demonstrate a pronounced negative differential resistance (NDR) effect, along with a current that is about ten times greater than that of the vdW type-III heterojunction. Moreover, the tunneling window of SiC/Ti2CO2 is only slightly altered when subjected to an external electric field and vertical strain, demonstrating the remarkable stability of its type-III band alignments. Our results indicate that the SiC/Ti2CO2 heterojunction is useful to construct high-performance TFETs, and also introduces new ideas to design TFETs by using type-III covalent-bond heterojunctions.

7.
Phys Chem Chem Phys ; 25(11): 8144-8152, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36877127

RESUMO

Z-scheme van der Waals heterojunctions are very attractive photocatalysts attributed to their excellent reduction and oxidation abilities. In this paper, we designed InN/XS2 (X = Zr, Hf) heterojunctions and explored their electronic structure properties, photocatalytic performance, and light absorption systematically using first-principles calculations. We found that the valence-band maximum (VBM) and conduction-band minimum (CBM) of the InN/XS2 (X = Zr, Hf) heterojunctions are contributed by InN and XS2, respectively. Photo-generated carriers transferring along the Z-path can accelerate the recombination of interlayer electron-hole pairs. Therefore, the photogenerated electrons in the CBM of the InN layer can be maintained making the hydrogen evolution reaction occur continuously, while photogenerated holes in the VBM of the Ti2CO2 layer make the oxygen evolution reaction occur continuously. The band edge positions of heterojunctions can straddle the required water redox potentials, while pristine InN and XS2 (X = Zr, Hf) can only be used for photocatalytic hydrogen evolution or oxygen evolution, respectively. Furthermore, the HER barriers can be tuned by transition metal doping. With Cr doping, the hydrogen evolution reaction (HER) barriers decrease to -0.12 for InN/ZrS2 and -0.05 eV for InN/HfS2, very close to the optimal value (0 eV). In addition, the optical absorption coefficient is as high as 105 cm-1 in the visible and ultraviolet regions. Therefore, the InN/XS2 (X = Zr, Hf) heterojunctions are expected to be excellent photocatalysts for water splitting.

8.
J Nanobiotechnology ; 21(1): 236, 2023 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-37482608

RESUMO

Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce tumor regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific and adverse side effects. However, the challenge in the field of therapeutic tumor vaccines is ensuring the delivery of immune components to the lymph nodes (LNs) to activate immune cells. The clinical response rate of traditional therapeutic tumor vaccines falls short of expectations due to inadequate lymph node delivery. With the rapid development of nanotechnology, a large number of nanoplatform-based LN-targeting nanovaccines have been exploited for optimizing tumor immunotherapies. In addition, some nanovaccines possess non-invasive visualization performance, which is benefit for understanding the kinetics of nanovaccine exposure in LNs. Herein, we present the parameters of nanoplatforms, such as size, surface modification, shape, and deformability, which affect the LN-targeting functions of nanovaccines. The recent advances in nanoplatforms with different components promoting LN-targeting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies to both improve targeting performance and enhance the quality of LN imaging are discussed. Finally, we summarize the prospects and challenges of nanoplatform-based LN-targeting and /or imaging strategies, which optimize the clinical efficacy of nanovaccines in tumor immunotherapies.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Linfonodos , Neoplasias/terapia , Imunoterapia , Nanotecnologia
9.
Proc Natl Acad Sci U S A ; 116(12): 5362-5369, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30837316

RESUMO

Lipid nanovesicles are widely present as transport vehicles in living organisms and can serve as efficient drug delivery vectors. It is known that the size and surface charge of nanovesicles can affect their diffusion behaviors in biological hydrogels such as mucus. However, how temperature effects, including those of both ambient temperature and phase transition temperature (Tm), influence vehicle transport across various biological barriers outside and inside the cell remains unclear. Here, we utilize a series of liposomes with different Tm as typical models of nanovesicles to examine their diffusion behavior in vitro in biological hydrogels. We observe that the liposomes gain optimal diffusivity when their Tm is around the ambient temperature, which signals a drastic change in the nanovesicle rigidity, and that liposomes with Tm around body temperature (i.e., ∼37 °C) exhibit enhanced cellular uptake in mucus-secreting epithelium and show significant improvement in oral insulin delivery efficacy in diabetic rats compared with those with higher or lower Tm Molecular-dynamics (MD) simulations and superresolution microscopy reveal a temperature- and rigidity-mediated rapid transport mechanism in which the liposomes frequently deform into an ellipsoidal shape near the phase transition temperature during diffusion in biological hydrogels. These findings enhance our understanding of the effect of temperature and rigidity on extracellular and intracellular functions of nanovesicles such as endosomes, exosomes, and argosomes, and suggest that matching Tm to ambient temperature could be a feasible way to design highly efficient nanovesicle-based drug delivery vectors.


Assuntos
Hidrogéis/administração & dosagem , Hidrogéis/química , Lipídeos/química , Nanopartículas/química , Animais , Transporte Biológico/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Difusão/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Epitélio/metabolismo , Insulina/administração & dosagem , Insulina/química , Lipossomos/química , Masculino , Transição de Fase/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Temperatura
10.
Neoplasma ; 68(3): 509-518, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33502891

RESUMO

This study aims to investigate the role of the long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in the regulation of anoikis resistance of ovarian cancer cells, a prerequisite for metastasis and chemoresistance in ovarian cancer cells. Ovarian cancer SKOV3 cells were cultured in an ultra-low attachment system to establish an anoikis model. The relationship between cellular anoikis capability and HOTAIR expression level was studied by flow cytometry and RT-PCR. The ability of spheroid formation, migration, and invasion of the suspended cells was assessed following the knockdown of HOTAIR expression. The expression of EZH2, H3K27me3, representative targets of EZH2, and anoikis-related biomarkers was also detected. An increase in the duration of suspension culture time rendered the SKOV3 cells anoikis-resistant with a significantly lower apoptotic rate compared to the adherent cells. HOTAIR expression in the suspension cells increased significantly, while that in the adherent cells did not. Following small interfering RNA (siRNA)-mediated knockdown of HOTAIR expression, the abilities of anoikis resistance, migration, and invasion decreased in the suspension cells. Knockdown of HOTAIR levels also reduced the spheroid forming ability of the tumor cells in continuous suspension cultures. Moreover, EZH2 expression correlated with HOTAIR expression, thus regulating the expression of miR-193a and DOK2 via introducing H3K27me3. Western blot analysis of anoikis-related markers showed that N-cadherin, ZEB1, and TWIST1 were downregulated following inhibition of HOTAIR, while E-cadherin and ErbB3 were upregulated. In conclusion, HOTAIR enhances the anoikis resistance and spheroid forming ability of ovarian cancer cells by recruiting EZH2 and influencing H3K27 methylation that may contribute to migration, invasion, and chemoresistance of ovarian cancer cells.


Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Anoikis/genética , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metilação , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
11.
Nano Lett ; 20(2): 936-946, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31671946

RESUMO

Despite rapid advancements in antitumor drug delivery, insufficient intracellular transport and subcellular drug accumulation are still issues to be addressed. Cancer cell membrane (CCM)-camouflaged nanoparticles (NPs) have shown promising potential in tumor therapy due to their immune escape and homotypic binding capacities. However, their efficacy is still limited due to inefficient tumor penetration and compromised intracellular transportation. Herein, a yolk-shell NP with a mesoporous silica nanoparticle (MSN)-supported PEGylated liposome yolk and CCM coating, CCM@LM, was developed for chemotherapy and exhibited a homologous tumor-targeting effect. The yolk-shell structure endowed CCM@LM with moderate rigidity, which might contribute to the frequent transformation into an ellipsoidal shape during infiltration, leading to facilitated penetration throughout multicellular spheroids in vitro (up to a 23.3-fold increase compared to the penetration of membrane vesicles). CCM@LM also exhibited a cellular invasion profile mimicking an enveloped virus invasion profile. CCM@LM was directly internalized by membrane fusion, and the PEGylated yolk (LM) was subsequently released into the cytosol, indicating the execution of an internalization pathway similar to that of an enveloped virus. The incoming PEGylated LM further underwent efficient trafficking throughout the cytoskeletal filament network, leading to enhanced perinuclear aggregation. Ultimately, CCM@LM, which co-encapsulated low-dose doxorubicin and the poly(ADP-ribose) polymerase inhibitor, mefuparib hydrochloride, exhibited a significantly stronger antitumor effect than the first-line chemotherapeutic drug Doxil. Our findings highlight that NPs that can undergo facilitated tumor penetration and robust intracellular trafficking have a promising future in cancer chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Linhagem Celular Tumoral , Membrana Celular/química , Vesículas Revestidas/química , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Dióxido de Silício/química , Esferoides Celulares/química
12.
BMC Oral Health ; 19(1): 181, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395103

RESUMO

BACKGROUND: The purpose of this experiment was to assess the push out bond strength of Polydimethylsiloxane sealers (GuttaFlow 2 and GuttaFlow Bioseal by Colte'ne/Whaledent, Altstätten, Switzerland). AH Plus (Dentsply, DeTrey, Konstanz, Germany) was used as a reference material for comparison. METHODS: Thirty root slices were prepared from the middle third of 10 mandibular premolars. Each slice was 1 ± 0.1 mm thick. Three holes, 0.8 mm wide each, were drilled on the axial side of each root slice. These holes were subjected to standardized irrigations and then dried using paper points. Finally, for each root slice, each hole was filled with exactly one of the following three root canal sealers: AH Plus, GuttaFlow 2 and GuttaFlow Bioseal. After all the holes were filled in that way, the root slices were stored on top of phosphate-buffered saline solution (pH 7.2) soaked gauze for 7 days at the temperature of 37 degrees Celsius. Then, for each root canal sealer on a root slice, the universal testing machine was used to measure the push out bond strength. The differences in push out bond strengths between the three sealer samples were assessed using the Friedman test, while the paired comparisons were assessed using Wilcoxon signed rank test with Bonferroni correction. All statistical tests were two-tailed and the significance level was set at the 5%. RESULTS: According to the Friedman test the distributions of push out bond strengths of AH Plus, GuttaFlow 2 and GuttaFlow Bioseal were different (P < 0.05). Paired comparisons indicated that AH Plus had a significantly superior push out bond strength than GuttaFlow 2 and GuttaFlow Bioseal, while the push out bond strength of GuttaFlow Bioseal was significantly stronger than that of GuttaFlow 2 (P < 0.01). CONCLUSIONS: Based on these findings, AH Plus is a better root canal sealer than GuttaFlow 2 and GuttaFlow Bioseal.


Assuntos
Colagem Dentária/métodos , Dimetilpolisiloxanos/química , Materiais Restauradores do Canal Radicular/química , Silicatos/uso terapêutico , Dentina/química , Combinação de Medicamentos , Resinas Epóxi , Guta-Percha , Humanos , Teste de Materiais , Materiais Restauradores do Canal Radicular/uso terapêutico , Irrigantes do Canal Radicular/química , Cimento de Óxido de Zinco e Eugenol
13.
Psychiatry Clin Neurosci ; 68(5): 357-64, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24393367

RESUMO

AIM: We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. METHODS: Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. RESULTS: At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. CONCLUSION: Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas.


Assuntos
Ácido Aspártico/análogos & derivados , Cerebelo/metabolismo , Transtorno Depressivo Maior/metabolismo , Giro do Cíngulo/metabolismo , Adolescente , Adulto , Antidepressivos/uso terapêutico , Ácido Aspártico/metabolismo , Colina/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Inositol/metabolismo , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
14.
World J Clin Cases ; 12(15): 2627-2635, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38817239

RESUMO

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an RET carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners. CASE SUMMARY: Herein, we present RET proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the RET proto-oncogene was conducted. The C634Y mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the C634Y mutation, and the corresponding treatments administered based on test results and associated clinical guidelines. CONCLUSION: Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.

15.
Adv Healthc Mater ; : e2401199, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054675

RESUMO

The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8+ and CD4+ T cells targeting specific antigens, reducing immunosuppression by regulatory T cells, and boosting the populations of effector memory T cells. These findings underscore that the simple yet potent strategy of employing minimal flexible nanocapsules markedly enhances DC-mediated antitumor immunotherapy, offering promising avenues for future clinical applications.

16.
Ultrasonography ; 42(2): 314-322, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36935592

RESUMO

PURPOSE: This study aimed to evaluate the diagnostic value of combined fine-needle aspiration (FNA) with core needle biopsy (CNB) in thyroid nodules. METHODS: FNA and CNB were performed simultaneously on 703 nodules. We compared the proportions of inconclusive results and the diagnostic performance for malignancy among FNA, CNB, and combined FNA/CNB for different nodule sizes. RESULTS: Combined FNA/CNB showed lower proportions of inconclusive results than CNB for all nodules (2.8% vs. 5.7%, P<0.001), nodules ≤1.0 cm (4.9% vs. 7.3%, P=0.063), nodules >1.0 cm (2.0% vs. 5.0 %, P<0.001), nodules ≤1.5 cm (3.8% vs. 7.9 %, P<0.001), and nodules >1.5 cm (2.1% vs. 3.9 %, P=0.016). The sensitivity of combined FNA/CNB in predicting malignancy was significantly higher than that of CNB (89.0% vs. 80.0%, P<0.001) and FNA (89.0% vs. 58.1%, P<0.001) for all nodules. Within American College of Radiology Thyroid and Imaging Reporting and Data System grades 4-5, in the subgroup of nodules ≤1.5 cm, combined FNA/ CNB showed the best sensitivity in predicting malignancy (91.4%), significantly higher than that of CNB (81.0%, P<0.001) and FNA (57.8%, P<0.001). However, in the subgroup of nodules >1.5 cm, the difference between combined FNA/CNB and CNB was not significant (84.2% vs. 78.9%, P=0.500). CONCLUSION: Regardless of nodule size, combined FNA/CNB tended to yield lower proportions of inconclusive results than CNB or FNA alone and exhibited higher performance in diagnosing malignancy. The combined FNA/CNB technique may be a more valuable diagnostic method for nodules ≤1.5 cm and nodules with a risk of malignancy than CNB and FNA alone.

17.
Clin Hemorheol Microcirc ; 83(4): 377-386, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744332

RESUMO

BACKGROUND: The inadequacy samples caused by the internal characteristic structure of thyroid nodules are difficult to be solved. OBJECTIVE: To evaluate the ultrasound features affecting the sample adequacy after fine-needle aspiration (FNA) of thyroid nodules with different risk stratification. METHODS: 592 thyroid nodules that underwent ultrasound-guided FNA were included in this retrospective study. The sample obtained by FNA were classified as inadequacy and adequacy according to the cytopathological results. Ultrasound features (ie., size, position, cystic predominance, composition, echo, shape, margin, and superficial annular calcification status) of the nodules were recorded and compared between the inadequacy sample group and adequacy sample group. RESULTS: Multiple logistic regression shows that preponderant cystic proportion (OR, 0.384; P = 0.041), extremely hypoechogenicity and hypoechogenicity (OR, 6.349; P = 0.006) were the independent influencing factors of inadequate samples after FNA in benign expected nodules. In addition, nodule size ≤10 mm (OR, 1.960; P = 0.010) and superficially annular calcification (OR, 4.600; P < 0.001) were independent influencing factors for inadequate samples after FNA in malignant expected nodules. CONCLUSION: The ultrasound features of hypoechogenicity or high cystic proportion in benign expected nodules and that of small size or annular calcification in malignant expected nodules were the risk factors for inadequacy samples by US-guided FNA.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina/métodos , Estudos Retrospectivos , Ultrassonografia , Medição de Risco , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia
18.
Comput Math Methods Med ; 2022: 1862396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756401

RESUMO

Background: In recent years, influenced by the continuous improvement and development of the medical service model and the increasing demands of modern people for the quality of clinical care, the clinical treatment of schizophrenic groups has also received widespread attention and importance from all sectors of society. Psychobehavioral care is administered to patients during active antipsychotic treatment, which can maximize the patient's cooperation with clinical work and thus play an auxiliary role in treatment. Aims: To investigate the impact of emotional-behavioral responses, cognitive changes in outpatient follow-up of schizophrenic patients with integrated psychobehavioral care. Materials and Methods: One hundred cases of schizophrenia patients with outpatient follow-up in our hospital from March 2017 to March 2019 were selected as prospective study subjects and divided into a comparison group and an observation group of 50 cases each according to a random number table. Among them, the comparison group implemented conventional psychobehavioral care, and the observation group implemented integrated psychobehavioral care. The differences in compliance behavior, negative emotions, cognitive behavioral changes, and pain scores before and after care of schizophrenia patients in the outpatient follow-up were compared between the two groups. Results: After care, the compliance behavior, negative emotions, cognitive behavioral changes, and pain scores of schizophrenia patients in both groups with outpatient follow-up were significantly improved and significantly higher in the observation group than in the comparison group, and statistics showed that this difference was statistically significant (P < 0.05). Conclusion: Integrated psychobehavioral care combined with conventional psychobehavioral care can effectively enhance the compliance behavior of outpatient follow-up schizophrenia patients, improve the negative emotions and pain of patients, and facilitate the active treatment of patients to improve their prognosis. It has some reference value for outpatient follow-up schizophrenia patient care.


Assuntos
Esquizofrenia , Cognição , Emoções , Humanos , Pacientes Ambulatoriais , Dor , Estudos Prospectivos , Esquizofrenia/tratamento farmacológico
19.
World J Clin Cases ; 10(33): 12319-12327, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36483813

RESUMO

BACKGROUND: Acute intermittent porphyria (AIP) is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase (HMBS) gene. This study aimed to explore the clinical manifestations of a patient with AIP, to identify a novel HMBS gene mutation in the proband and some of her family members, and to confirm the pathogenicity of the variant. CASE SUMMARY: A 22-year-old Chinese woman developed severe abdominal pain, lumbago, sinus tachycardia, epileptic seizure, hypertension, and weakness in lower limbs in March, 2018. Biochemical examinations indicated hypohepatia and hyponatremia. Her last menstrual period was 45 d prior to admission, and she was unaware of the pregnancy, which was confirmed by a pregnancy test after admission. Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red. Urinary porphyrin test result was positive. Based on these clinical manifestations, AIP was diagnosed. After increasing her daily glucose intake (250-300 g/d), abdominal pain was partially relieved. Three days after hospitalization, spontaneous vaginal bleeding occurred, which was confirmed as spontaneous abortion; thereafter, her clinical symptoms completely resolved. Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10 (c.648_651+1delCCAGG) in the proband and four other family members. The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay. CONCLUSION: We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.

20.
Zhonghua Gan Zang Bing Za Zhi ; 19(7): 542-6, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22152248

RESUMO

OBJECTIVE: To investigate the relationship of NOR-1 with the inhibition of inflammatory reaction in mice Kupffer cells (KCs) induced by lipopolysaccharide (LPS) via liver X receptor alpha (LXR alpha). METHODS: KCs from male KM mice were isolated by density gradient centrifugation, incubated and then randomly assigned to three groups: control group, LPS treated group and LPS+T0901317 treated group. RESULTS: The mRNA and protein expressions of LXR alpha and NOR-1 in each group were determined by RT-PCR, immunofluorescent assay and western blot, respectively. The densities of TNF alpha and IL-10 in supernatants were evaluated by enzyme linked immunosorbent assay (ELISA). The mRNA and protein expression levels of LXR alpha in LPS + T0901317 group were the highest as compared to the other two groups (0.748+/-0.072 and 1.217+/-0.133 respectively), The mRNA and protein expression levels of NOR-1 in LPS+ T0901317 group were the highest as compared to the other two groups (2.726+/-0.065 and 0.842+/-0.058 respectively). The densities of supernatant TNF alpha in LPS group and IL-10 in LPS+T0901317 group were the highest [(450.89+/-78.52) ng/L and (537.41+/-36.41) ng/L respectively]. CONCLUSIONS: Promoting the expression of LXR alpha in KCs can elevate the NOR-1 expression and then inhibit inflammatory reaction.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Inflamação/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores Nucleares Órfãos/metabolismo , Receptores de Esteroides/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Animais , Células Cultivadas , Interleucina-10/metabolismo , Células de Kupffer/metabolismo , Receptores X do Fígado , Masculino , Camundongos , Camundongos Endogâmicos , Fator de Necrose Tumoral alfa/metabolismo
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