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1.
Front Oncol ; 14: 1447828, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267851

RESUMO

Objective: To evaluate the antitumor effects of diisopropylamine dichloroacetate (DADA) alone or in combination with chemotherapy/radiotherapy/immunotherapy in NSCLC and explore the underlying mechanisms involved. Methods: MTT, UV spectrophotometry, flow cytometry, fluorescence microscopy, and clonogenic survival assays were used. In LLC mouse models, the antitumor effects of radiotherapy, DADA, and the anti-PD-1 antibody alone or in combination were evaluated, and the T cell numbers were evaluated in different groups. Results: DADA significantly inhibited lactate production and promoted apoptosis in NSCLC in vitro. Compared with pemetrexed or DADA alone, the combination of DADA with pemetrexed significantly inhibited proliferation and promoted apoptosis (p<0.05). This may be related to the decrease in the mitochondrial membrane potential in the combined group. Moreover, compared with radiotherapy alone, the combination of DADA with radiotherapy induced remarkable DNA damage. In vivo, the combination of radiotherapy, an anti-PD-1 antibody and DADA resulted in superior tumor inhibition than the combination of radiotherapy and anti-PD-1 antibody did (p < 0.05). The underlying mechanism may be partially related to the increased number of CD3+ T cells in the triplet combination group (p < 0.05). Discussion: Our results showed that DADA has strong antitumor effects on NSCLC, either alone or in combination with chemotherapy or radiotherapy. Interestingly, the combination of radiotherapy, anti-PD-1 antibody and DADA had a more pronounced tumor-suppressing effect, which may be related to DADA-induced T-cell generation by reducing local lactic acid production in the tumor microenvironment. This study lays the foundation for further exploration of DADA in lung cancer, especially in the era of immunotherapy, on the basis of its possible immunomodulatory effects.

2.
Clin Med Insights Oncol ; 18: 11795549241272654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233761

RESUMO

Background: Patients with gastric cancer (GC) who underwent radical surgery require long-term follow-up (usually 5 years). The purpose of this study was to explore individualized follow-up strategies for patients with GC. Methods: This is a retrospective cohort study that established a clinicopathologic database of patients who underwent gastrectomy from January 2010 to December 2020 at Ningbo No. 2 Hospital. Follow-up was performed until March 2023. The rate of new-onset recurrence of patients with GC was explored annually according to different pTNM stages, defining a recurrence rate of less than 1% as adequate follow-up time. Results: Of the 1606 patients who were eligible, the total number of patients who completed the 5- and 10-year follow-up was 1107 and 586, respectively. A total of 444 cases were diagnosed with recurrence. The recurrence rate for stage IA patients was consistently less than 1% during the follow-up time. The adequate follow-up time (the rate of new-onset recurrence less than 1%) was 5 years for stage IB and IIA patients, and 8 years for stage IIB and IIIA patients, respectively. In contrast, stage IIIB patients were always at risk of recurrence during the follow-up time (>1%). Time to a new recurrence rate for stage IIIC patients was 6 years. Conclusion: Among patients who underwent radical gastrectomy, the rate of new-onset recurrence varied among patients with different pTNM stages. This study suggests that the follow-up of GC can be individualized and refer to pTNM stage.

3.
Brain Res ; 1845: 149135, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39155035

RESUMO

Vascular dementia (VD) is a disease characterized by cognitive impairment and memory loss due to brain cell damage caused by cerebral vascular ischemia. Danggui-Shaoyao-San (DSS) has been used clinically to treat diseases for centuries. The VD model was established by bilateral common carotid artery (BCCA) repeated ischemia-reperfusion (I/R) and caudal bleeding. Target prediction of DSS and miR-124 in PI3K/Akt signaling pathway by network pharmacology. The effect of DSS on cognitive dysfunction were evaluated through methods such as behavioral experiments, cerebral blood flow monitoring, HE and Nissl staining, western blot, and q-PCR. Prediction result showed that both DSS and miR-124 could target Akt1. DSS treatment significantly reduced hippocampal cell damage, improved learning and memory ability. Mechanically, DSS treatment up-regulated the expression levels of PI3K and Akt protein, and its gene. Bcl-2/Bax index is up-regulated and cell apoptosis reduced. LC3II/LC3I index decreased and autophagy of brain cells increased. Moreover, DSS down-regulated the expression level of miR-124. And inhibition of miR-124 up-regulate the expression of PI3K, Akt. These results suggested that DSS can reduce the content of miR-124 in the hippocampus of VD mice, thus regulating the PI3K/Akt signaling pathway and improving the learning and memory ability of VD mice.

4.
Nano Lett ; 24(34): 10592-10598, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39137095

RESUMO

Monolayer transition metal dichalcogenide semiconductors exhibit unique valleytronic properties interacting strongly with chiral phonons that break time-reversal symmetry. Here, we observed the ultrafast dynamics of linearly and circularly polarized E'(Γ) phonons at the Brillouin zone center in single-crystalline monolayer WS2, excited by intense, resonant, and polarization-tunable terahertz pulses and probed by time-resolved anti-Stokes Raman spectroscopy. We separated the coherent phonons producing directional sum-frequency generation from the incoherent phonon population emitting scattered photons. The longer incoherent population lifetime than what was expected from coherence lifetime indicates that inhomogeneous broadening and momentum scattering play important roles in phonon decoherence at room temperature. Meanwhile, the faster depolarization rate in circular bases than in linear bases suggests that the eigenstates are linearly polarized due to lattice anisotropy. Our results provide crucial information for improving the lifetime of chiral phonons in two-dimensional materials and potentially facilitate dynamic control of spin-orbital polarizations in quantum materials.

5.
NPJ Parkinsons Dis ; 10(1): 146, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107320

RESUMO

TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson's disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5'-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.

6.
J Hazard Mater ; 476: 135120, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38976960

RESUMO

The decommissioning of nuclear reactors is a global concern, in part because of the generation of radioactive aerosols that can lead to internal radiation exposure. At present, radioactive aerosols generated during nuclear decommissioning have not been actively studied, and data collected from the actual decommissioning are limited. This paper presents a study of radioactive aerosols generated during the pre-decommission phase of an experimental shielding reactor. Among all the on-site operations, cutting resulted in the highest levels of radioactivity. Plasma arc cutting, in particular, had a maximum gross α and ß radioactivity over 0.10 and 0.14 Bq/m3, respectively. Assumed AMAD (activity median aerodynamic diameter) values are employed to assess the impact of particle size on the internal exposure dose resulting from the inhalation of 137Cs aerosols. This assessment is based on the Human Respiratory Tract Model of International Commission on Radiological Protection. When cutting stainless steel by plasma arc, the internal exposure dose caused by 137Cs aerosols with an AMAD of 0.1 µm is estimated to be nearly four times as that of aerosols with an AMAD of 10 µm. Results show that the internal exposure dose is highly dependent on the AMAD, implying the importance of measuring size-related parameters of radioactive aerosols in the future nuclear decommissioning. This study has revealed some characteristics of radioactive aerosols released in decommissioning operations, which can serve as a valuable reference for controlling and removing aerosols during the decommissioning of nuclear facilities.

7.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000025

RESUMO

3,4-disubstituted maleimides find wide applications in various pharmacologically active compounds. This study presents a highly effective approach for synthesizing derivatives of 3,4-disubstituted maleimides through the direct isomerization of α-succinimide-substituted allenoates, followed by a cascade γ'-addition and aryl imines using PR3 as a catalyst. The resulting series of 3,4-disubstituted maleimides exhibited excellent stereoselectivities, achieving yields of up to 86%. To our knowledge, the phosphine-mediated γ'-addition reaction of allenoates is seldom reported.


Assuntos
Iminas , Maleimidas , Fosfinas , Succinimidas , Maleimidas/química , Maleimidas/síntese química , Fosfinas/química , Catálise , Iminas/química , Succinimidas/química , Estereoisomerismo , Estrutura Molecular , Isomerismo
8.
Sensors (Basel) ; 24(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000870

RESUMO

In recent years, advancements in the Internet of Things (IoT), manufacturing processes, and material synthesis technologies have positioned flexible sensors as critical components in wearable devices. These developments are propelling wearable technologies based on flexible sensors towards higher intelligence, convenience, superior performance, and biocompatibility. Recently, two-dimensional nanomaterials known as MXenes have garnered extensive attention due to their excellent mechanical properties, outstanding electrical conductivity, large specific surface area, and abundant surface functional groups. These notable attributes confer significant potential on MXenes for applications in strain sensing, pressure measurement, gas detection, etc. Furthermore, polymer substrates such as polydimethylsiloxane (PDMS), polyurethane (PU), and thermoplastic polyurethane (TPU) are extensively utilized as support materials for MXene and its composites due to their light weight, flexibility, and ease of processing, thereby enhancing the overall performance and wearability of the sensors. This paper reviews the latest advancements in MXene and its composites within the domains of strain sensors, pressure sensors, and gas sensors. We present numerous recent case studies of MXene composite material-based wearable sensors and discuss the optimization of materials and structures for MXene composite material-based wearable sensors, offering strategies and methods to enhance the development of MXene composite material-based wearable sensors. Finally, we summarize the current progress of MXene wearable sensors and project future trends and analyses.

9.
Molecules ; 29(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38893468

RESUMO

In this paper, an interesting γ'-carbon 1,6-conjugate addition for phosphine-catalyzed α-succinimide substituted allenoates has been disclosed. A wide array of substrates was found to participate in the reaction, resulting in the production of diverse 4-diarylmethylated 3,4-disubstituted maleimides with satisfactory to outstanding yields. Furthermore, a plausible mechanism for the reaction was proposed by the investigators.

10.
Materials (Basel) ; 17(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38893890

RESUMO

Vat photopolymerization (VP), as an additive manufacturing process, has experienced significant growth due to its high manufacturing precision and excellent surface quality. This method enables the fabrication of intricate shapes and structures while mitigating the machining challenges associated with non-oxide ceramics, which are known for their high hardness and brittleness. Consequently, the VP process of non-oxide ceramics has emerged as a focal point in additive manufacturing research areas. However, the absorption, refraction, and reflection of ultraviolet light by non-oxide ceramic particles can impede light penetration, leading to reduced curing thickness and posing challenges to the VP process. To enhance the efficiency and success rate of this process, researchers have explored various aspects, including the parameters of VP equipment, the composition of non-oxide VP slurries, and the surface modification of non-oxide particles. Silicon carbide and silicon nitride are examples of non-oxide ceramic particles that have been successfully employed in VP process. Nonetheless, there remains a lack of systematic induction regarding the curing mechanisms and key influencing factors of the VP process in non-oxide ceramics. This review firstly describes the curing mechanism of the non-oxide ceramic VP process, which contains the chain initiation, chain polymerization, and chain termination processes of the photosensitive resin. After that, the impact of key factors on the curing process, such as the wavelength and power of incident light, particle size, volume fraction of ceramic particles, refractive indices of photosensitive resin and ceramic particles, incident light intensity, critical light intensity, and the reactivity of photosensitive resins, are systematically discussed. Finally, this review discusses future prospects and challenges in the non-oxide ceramic VP process. Its objective is to offer valuable insights and references for further research into non-oxide ceramic VP processes.

11.
J Neuroinflammation ; 21(1): 143, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822367

RESUMO

The dysregulation of pro- and anti-inflammatory processes in the brain has been linked to the pathogenesis of major depressive disorder (MDD), although the precise mechanisms remain unclear. In this study, we discovered that microglial conditional knockout of Pdcd4 conferred protection against LPS-induced hyperactivation of microglia and depressive-like behavior in mice. Mechanically, microglial Pdcd4 plays a role in promoting neuroinflammatory responses triggered by LPS by inhibiting Daxx-mediated PPARγ nucleus translocation, leading to the suppression of anti-inflammatory cytokine IL-10 expression. Finally, the antidepressant effect of microglial Pdcd4 knockout under LPS-challenged conditions was abolished by intracerebroventricular injection of the IL-10 neutralizing antibody IL-10Rα. Our study elucidates the distinct involvement of microglial Pdcd4 in neuroinflammation, suggesting its potential as a therapeutic target for neuroinflammation-related depression.


Assuntos
Proteínas Correpressoras , Interleucina-10 , Camundongos Knockout , Microglia , Doenças Neuroinflamatórias , PPAR gama , Transdução de Sinais , Animais , Masculino , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Depressão/metabolismo , Depressão/etiologia , Interleucina-10/metabolismo , Interleucina-10/deficiência , Interleucina-10/genética , Lipopolissacarídeos/toxicidade , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/efeitos dos fármacos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Doenças Neuroinflamatórias/metabolismo , PPAR gama/metabolismo , PPAR gama/genética , Transdução de Sinais/fisiologia , Transdução de Sinais/efeitos dos fármacos
12.
ACS Appl Mater Interfaces ; 16(26): 34089-34099, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38888573

RESUMO

Slippery liquid-infused porous surfaces (SLIPSs) have great potential to replace traditional antifouling coatings due to their efficient, green, and broad-spectrum antifouling performance. However, the lubricant dissipation problem of SLIPS severely restricts its further development and application, and the robust SLIPS continues to be extremely challenging. Here, a composite phase-change lubricant layer consisting of paraffin, silicone oil, and MXene is designed to readily construct a stable and NIR-responsive self-healing phase-change solid slippery surface (PCSSS). Collective results showed that PCSSS could rapidly achieve phase-change transformation and complete self-healing under NIR irradiation and keep stable after high-speed water flushing, centrifugation, and ultrasonic treatment. The antifouling performance of PCSSS evaluated by protein, bacteria, and algae antiadhesion tests demonstrated the adhesion inhibition rate was as high as 99.99%. Moreover, the EIS and potentiodynamic polarization experiments indicated that PCSSS had stable and exceptional corrosion resistance (|Z|0.01Hz = 3.87 × 108 Ω·cm2) and could effectively inhibit microbiologically influenced corrosion. The 90 day actual marine test reveals that PCSSS has remarkable antifouling performance. Therefore, PCSSS presents a novel, facile, and effective strategy to construct a slippery surface with the prospect of facilitating its application in marine antifouling and corrosion protection.

13.
Plant Sci ; 346: 112160, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38908800

RESUMO

Vegetative propagation through cutting is a widely used clonal approach for maintaining desired genotypes. However, some woody species have difficulty forming adventitious roots (ARs) with this approach, including yellow camellia (YC) C. nitidissima. Yellow camellias, prized for their ornamental value and potential health benefits in tea, remain difficult to propagate clonally due to this rooting recalcitrance. As part of the efforts to understand YC cuttings' recalcitrance, we conducted a detailed investigation into AR formation in yellow camellia cuttings via histology and endogenous phytohormone dynamics during this process. We also compared YC endogenous phytohormone and metabolite phytohormone profiles with those of easy-to-root poplar and willow cuttings. Our results indicate that the induction of ARs in YC cuttings is achievable through auxin treatment, and YC ARs are initiated from cambial derivatives and develop a vascular system connected with that of the stem. During AR induction, endogenous hormones showed a dynamic profile, with IAA continuing to increase starting 9 days after auxin induction. JA, JA-Ile, and OPDA showed a similar trend as IAA but decreased by the 45th day. Cytokinin first decreased to its lowest level by the 18th day and then increased. SA largely exhibited an increasing trend with a drop on the 36th day, while ABA first increased to its peak level by the 18th day and then decreased. Compared to poplar, YC cuttings had a low level of IAA, IAA-Asp, and OPDA, and a high level of cytokinin and SA. Metabolite profiling highlighted significant down-accumulation of compounds associated with AR formation in yellow camellias, such as citric and ascorbic acid, fructose, sucrose, flavonoids, and phenolic acid derivatives. Our study reveals the unfavorable endogenous hormone and metabolite profiles underlying the rooting recalcitrance of YC cuttings, providing valuable knowledge for addressing this challenge in clonal propagation.


Assuntos
Camellia , Reguladores de Crescimento de Plantas , Raízes de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Camellia/metabolismo , Camellia/genética , Camellia/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo
14.
Plant Biotechnol J ; 22(9): 2541-2557, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38715250

RESUMO

MicroRNA169 (miR169) has been implicated in multi-stress regulation in annual species such as Arabidopsis, maize and rice. However, there is a lack of experimental functional and mechanistic studies of miR169 in plants, especially in perennial species, and its impact on plant growth and development remains unexplored. Creeping bentgrass (Agrostis stolonifera L.) is a C3 cool-season perennial turfgrass of significant environmental and economic importance. In this study, we generated both miR169 overexpression and knockdown transgenic creeping bentgrass lines. We found that miR169 acts as a positive regulator in abiotic stress responses but is negatively associated with plant growth and development, playing multiple critical roles in the growth and environmental adaptation of creeping bentgrass. These roles include differentiated spatial hormone accumulation patterns associated with growth and stress accommodation, elevated antioxidant activity that alleviates oxidative damage induced by stress, ion-channelling membrane components for maintaining homeostasis under saline conditions, and potential cross-talks with stress-regulating transcription factors such as AsHsfA and AsWRKYs. Our results unravel the role of miR169 in modulating plant development and stress responses in perennial grass species. This underlines the potential of manipulating miR169 to generate crop cultivars with desirable traits to meet diverse agricultural demands.


Assuntos
Agrostis , Regulação da Expressão Gênica de Plantas , MicroRNAs , Estresse Fisiológico , Agrostis/genética , Agrostis/crescimento & desenvolvimento , Agrostis/fisiologia , Agrostis/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Plantas Geneticamente Modificadas/genética , RNA de Plantas/genética , RNA de Plantas/metabolismo
15.
J Nanobiotechnology ; 22(1): 275, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778401

RESUMO

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.


Assuntos
Gota , Indóis , Polímeros , Espécies Reativas de Oxigênio , Ácido Úrico , Gota/tratamento farmacológico , Gota/metabolismo , Gota/terapia , Espécies Reativas de Oxigênio/metabolismo , Animais , Camundongos , Polímeros/química , Indóis/química , Indóis/farmacologia , Nanopartículas/química , Platina/química , Platina/farmacologia , Platina/uso terapêutico , Humanos , Peróxido de Hidrogênio/metabolismo , Hipertermia Induzida/métodos , Células RAW 264.7 , Terapia Fototérmica/métodos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Masculino
16.
ACS Nano ; 18(19): 12194-12209, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38689426

RESUMO

In situ vaccines (ISVs) utilize the localized delivery of chemotherapeutic agents or radiotherapy to stimulate the release of endogenous antigens from tumors, thereby eliciting systemic and persistent immune activation. Recently, a bioinspired ISV strategy has attracted tremendous attention due to its features such as an immune adjuvant effect and genetic plasticity. M13 bacteriophages are natural nanomaterials with intrinsic immunogenicity, genetic flexibility, and cost-effectiveness for large-scale production, demonstrating the potential for application in cancer vaccines. In this study, we propose an ISV based on the engineered M13 bacteriophage targeting CD40 (M13CD40) for dendritic cell (DC)-targeted immune stimulation, named H-GM-M13CD40. We induce immunogenic cell death and release tumor antigens through local delivery of (S)-10-hydroxycamptothecin (HCPT), followed by intratumoral injection of granulocyte-macrophage colony stimulating factor (GM-CSF) and M13CD40 to enhance DC recruitment and activation. We demonstrate that this ISV strategy can result in significant accumulation and activation of DCs at the tumor site, reversing the immunosuppressive tumor microenvironment. In addition, H-GM-M13CD40 can synergize with the PD-1 blockade and induce abscopal effects in cold tumor models. Overall, our study verifies the immunogenicity of the engineered M13CD40 bacteriophage and provides a proof of concept that the engineered M13CD40 phage can function as an adjuvant for ISVs.


Assuntos
Bacteriófago M13 , Vacinas Anticâncer , Células Dendríticas , Microambiente Tumoral , Vacinas Anticâncer/imunologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Bacteriófago M13/imunologia , Bacteriófago M13/química , Camundongos , Células Dendríticas/imunologia , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Linhagem Celular Tumoral , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Antígenos de Neoplasias/imunologia , Humanos
17.
Front Pediatr ; 12: 1379168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808103

RESUMO

Objective: This study aims to retrospectively analyze the epidemiological and clinical characteristics of acute intussusception in a tertiary-care pediatric hospital in China over 4 years and evaluate the effectiveness and recurrence of fluoroscopy-guided pneumatic reduction (FGPR) and ultrasound-guided hydrostatic reduction (UGHR). Methods: This retrospective study was conducted from January 2019 to December 2022 involving children admitted and managed for acute intussusception in a tertiary-care pediatric hospital in China. The epidemiology, clinical features, and therapeutic effects were analyzed using IBM SPSS Statistics 20.0. Results: The study included 401 boys (68.43%) and 185 girls (31.57%) aged from 2 months to 12 years. The most common symptoms reported were abdominal pain or paroxysmal crying (95.73%), vomiting (45.39%), and bloody stool (7.34%). Vomiting and bloody stool became atypical with increasing age (P < 0.001). The total success cases of reduction accounted for 563 cases (96.08%), and the recurrent cases accounted for 71 cases (12.12%). No significant difference was observed in the success or recurrence rates between FGPR and UGHR (P > 0.05). Abdominal pain was an independent protective factor for successful enema (P < 0.01, OR = 72.46), while bloody stool (P < 0.01, OR = 0.06) and older age were independent risk factors (P < 0.001, OR = 0.51). Of the 71 patients with recurrent intussusception, 29 were successfully reduced by enema, and the other 23 required surgical reduction. Twelve of the surgical cases were secondary intussusception, including three cases of Meckel's diverticulum, five cases of polyps, and four cases of non-Hodgkin lymphoma. Conclusion: The epidemiological characteristics of children with intussusception in Xiamen showed peculiarity with a higher male-to-female ratio, older age at diagnosis, and no significant seasonality. Both FGPR and UGHR were effective and safe for intussusception, and surgical reduction was essential for patients with failed enema reduction.

18.
Foods ; 13(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611336

RESUMO

Ulcerative colitis (UC) is a complicated inflammatory disease with a continually growing incidence. In this study, resistant starch was obtained from purple sweet potato (PSPRS) by the enzymatic isolation method. Then, the structural properties of PSPRS and its protective function in dextran sulfate sodium (DSS)-induced colitis were investigated. The structural characterization results revealed that the crystallinity of PSPRS changed from CA-type to A-type, and the lamellar structure was totally destroyed during enzymatic hydrolysis. Compared to DSS-induced colitis mice, PSPRS administration significantly improved the pathological phenotype and colon inflammation in a dose-dependent manner. ELISA results indicated that DSS-induced colitis mice administered with PSPRS showed higher IL-10 and IgA levels but lower TNF-α, IL-1ß, and IL-6 levels. Meanwhile, high doses (300 mg/kg) of PSPRS significantly increased the production of acetate, propionate, and butyrate. 16S rDNA high-throughput sequencing results showed that the ratio of Firmicutes to Bacteroidetes and the potential probiotic bacteria levels were notably increased in the PSPRS treatment group, such as Lactobacillus, Alloprevotella, Lachnospiraceae_NK4A136_group, and Bifidobacterium. Simultaneously, harmful bacteria like Bacteroides, Staphylococcus, and Akkermansia were significantly inhibited by the administration of a high dose of PSPRS (p < 0.05). Therefore, PSPRS has the potential to be a functional food for promoting intestinal health and alleviating UC.

19.
Mol Ther Oncol ; 32(2): 200790, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38595980

RESUMO

N5-methylcytosine (m5C) methylation modification plays a crucial role in the epigenetic mechanisms underlying tumorigenesis, aggressiveness, and malignancy in diffuse glioma. Our study aimed to develop a novel prognostic risk-scoring system to assess the impact of m5C modification in glioma patients. Initially, we identified two distinct m5C clusters based on the expression level of m5C regulators in The Cancer Genome Atlas glioblastoma (TCGA-GBM) dataset. Differentially expressed genes (DEGs) between the two m5C cluster groups were determined. Utilizing these m5C regulation-related DEGs, we classified glioma patients into three gene cluster groups: A, B, and C. Subsequently, an m5C scoring system was developed through a univariate Cox regression model, quantifying the m5C modification patterns utilizing six DEGs associated with disease prognosis. The resulting scoring system allowed us to categorize patients into high- or low-risk groups based on their m5C scores. In test (TCGA-GBM) and validation (Chinese Glioma Genome Atlas [CGGA]-1018 and CGGA-301) datasets, glioma patients with a higher m5C score consistently exhibited shorter survival durations, fewer isocitrate dehydrogenase (IDH) mutations, less 1p/19q codeletion and higher World Health Organization (WHO) grades. Additionally, distinct immune cell infiltration characteristics were observed among different m5C cluster groups and risk groups. Our study developed a novel prognostic scoring system based on m5C modification patterns for glioma patients, complementing existing molecular classifications and providing valuable insights into prognosis for glioma patients.

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