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1.
FASEB J ; 38(7): e23594, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38573451

RESUMEN

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.


Asunto(s)
Osteoartritis , Oxígeno , Animales , Ratas , Microtomografía por Rayos X , Hipoxia , Osteoartritis/etiología , Remodelación Ósea
2.
J Cell Mol Med ; 28(16): e70014, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39153211

RESUMEN

Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease-specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D' (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G-protein signalling 4 (RGS4) expression was significantly up-regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high-quality candidate compounds for treatment in ATC.


Asunto(s)
Apoptosis , Proliferación Celular , Proteínas RGS , Saponinas , Transducción de Señal , Espirostanos , Carcinoma Anaplásico de Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Saponinas/farmacología , Proteínas RGS/metabolismo , Proteínas RGS/genética , Proliferación Celular/efectos de los fármacos , Animales , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Espirostanos/farmacología , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/metabolismo , Ratones Desnudos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Metástasis de la Neoplasia
3.
J Cell Mol Med ; 28(10): e18385, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38801405

RESUMEN

Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.


Asunto(s)
Autofagia , Necrosis de la Cabeza Femoral , Glucocorticoides , Litio , Osteoblastos , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Autofagia/efectos de los fármacos , Glucocorticoides/farmacología , Glucocorticoides/efectos adversos , Ratas , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/tratamiento farmacológico , Necrosis de la Cabeza Femoral/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , Litio/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Masculino , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-akt/metabolismo , Modelos Animales de Enfermedad , Fosfatidilinositol 3-Quinasas/metabolismo , Cabeza Femoral/patología , Cabeza Femoral/efectos de los fármacos , Cabeza Femoral/metabolismo , Osteonecrosis/inducido químicamente , Osteonecrosis/patología , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/metabolismo , Osteonecrosis/prevención & control
4.
Immunology ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174487

RESUMEN

Personalized neoantigen therapy has shown long-term and stable efficacy in specific patient populations. However, not all patients have sufficient levels of neoantigens for treatment. Although somatic mutations are commonly found in tumours, a significant portion of these mutations do not trigger an immune response. Patients with low mutation burdens continue to exhibit unresponsiveness to this treatment. We propose a design paradigm for neoantigen vaccines by utilizing the highly immunogenic unnatural amino acid p-nitrophenylalanine (pNO2Phe) for sequence alteration of somatic mutations that failed to generate neoepitopes. This enhances the immunogenicity of the mutations and transforms it into a suitable candidate for immunotherapy. The nitrated altered epitope vaccines designed according to this paradigm is capable of activating circulating CD8+ T cells and inducing immune cross-reactivity against autologous mutated epitopes in different MHC backgrounds (H-2Kb, H-2Kd, and human HLA-A02:01), leading to the elimination of tumour cells carrying the mutation. After immunization with the altered epitopes, tumour growth was significantly inhibited. It is noteworthy that nitrated epitopes induce tumour-infiltrating macrophages to differentiate into the M1 phenotype, surprisingly enhancing the MHC II molecule presenting pathway of macrophages. Nitrated epitope-treated macrophages have the potential to cross-activate CD4+ and CD8+ T cells, which may explain why pNO2Phe can enhance the immunogenicity of epitopes. Meanwhile, the immunosuppressive microenvironment of the tumour is altered due to the activation of macrophages. The nitrated neoantigen vaccine strategy enables the design of vaccines targeting non-immunogenic tumour mutations, expanding the pool of potential peptides for personalized and shared novel antigen therapy. This approach provides treatment opportunities for patients previously ineligible for new antigen vaccine therapy.

5.
Cancer Immunol Immunother ; 73(8): 150, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832948

RESUMEN

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I , Mutación , Neoplasias , Receptores de Antígenos de Linfocitos T , Humanos , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/genética , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/genética , Inmunoterapia/métodos , Antígeno HLA-A11/genética , Antígeno HLA-A11/inmunología , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Antígenos de Neoplasias/inmunología , Antígenos de Neoplasias/genética , Línea Celular Tumoral
6.
Small ; 20(22): e2307961, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38126911

RESUMEN

Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.


Asunto(s)
Inmunoterapia , Manganeso , Terapia Fototérmica , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/terapia , Inmunoterapia/métodos , Manganeso/química , Humanos , Animales , Terapia Fototérmica/métodos , Línea Celular Tumoral , Femenino , Imagen por Resonancia Magnética/métodos , Ratones , Microambiente Tumoral , Nanopartículas/química , Fototerapia/métodos
7.
J Transl Med ; 22(1): 381, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654380

RESUMEN

BACKGROUND: Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death. METHODS: We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose. RESULTS: MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis. CONCLUSION: The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC.


Asunto(s)
Aprendizaje Automático , Mitocondrias , Neoplasias Gástricas , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Mitocondrias/metabolismo , Pronóstico , Estudios de Cohortes , Masculino , Femenino , Modelos Biológicos , Proliferación Celular , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Multiómica
8.
Phys Rev Lett ; 132(10): 104001, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38518322

RESUMEN

Phototaxis phenomenon is fundamental and critical for optical manipulation of micro-objects. Here, we report the size-dependent negative or positive phototaxis behaviors for microdroplets containing interfacial energy absorber flying in a laser. The critical diameters for such negative-to-positive turnover are studied through both experiments and simulation with different liquids and absorbers, which establishes the mechanism and reveals the role of both the liquid and the absorber inside the microdroplets. This study offers new insight for the manipulation of the phototaxis behavior of micro-objects, showing potential applications in optical trapping and transporting systems that involve light-microdroplet interactions.

9.
J Chem Inf Model ; 64(15): 5931-5943, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39042485

RESUMEN

Vast published dielectric ceramics literature is a natural database for big-data analysis, discovering structure-property relationships, and property prediction. We constructed a data-mining pipeline based on natural language processing (NLP) to extract property information from about 12,900 published dielectric ceramics articles and normalized more than 20 properties. The micro-F1 scores for sentence classification, named entities recognition, relation extraction (related), and relation extraction (same), are 91.6, 82.4, 91.4, and 88.3%, respectively. We demonstrated the distribution of some essential properties according to the publication years to reveal the tendency. In order to test the reliability of the data extraction, we trained an XGBoost model to predict the dielectric constant and used the SHAP module to interpret the contribution of each feature in order to identify some of the factors that determine the dielectric properties. The result shows that including Q × f in the model can increase the dielectric constant prediction accuracy. Our work can give some hints to experimentalists on their way to improve the performances of cutting-edge materials.


Asunto(s)
Cerámica , Minería de Datos , Minería de Datos/métodos , Cerámica/química , Procesamiento de Lenguaje Natural , Bases de Datos Factuales
10.
Macromol Rapid Commun ; 45(5): e2300559, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38014713

RESUMEN

Alveolar bone injury under diabetic conditions can severely impede many oral disease treatments. Rebuilding diabetic alveolar bone in clinics is currently challenging due to persistent infection and inflammatory response. Here, an antibacterial DNA-based hydrogel named Agantigel is developed by integrating silver nanoclusters (AgNCs) and tumor necrosis factor-alpha (TNF-α) antibody into DNA hydrogel to promote diabetic alveolar bone regeneration. Agantigel can effectively inhibit bacterial growth through AgNCs while exhibiting negligible cytotoxicity in vitro. The sustained release of TNF-α antibody from Agantigel effectively blocks TNF-α and promotes M2 polarization of macrophages, ultimately accelerating diabetic alveolar bone regeneration in vivo. After 21 days of treatment, Agantigel significantly accelerates the defect healing rate of diabetic alveolar bone up to 82.58 ± 8.58% and improves trabecular architectures compared to free TNF-α (42.52 ± 15.85%). The results imply that DNA hydrogels are potential bio-scaffolds helping the sustained release of multidrug for treating DABI or other oral diseases.


Asunto(s)
Diabetes Mellitus , Hidrogeles , Humanos , Hidrogeles/farmacología , Factor de Necrosis Tumoral alfa , Preparaciones de Acción Retardada , Antibacterianos/farmacología , ADN
11.
Molecules ; 29(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39202857

RESUMEN

This study utilized gas chromatography-ion mobility spectrometry (GC-IMS) to analyze the volatile flavor compounds present in various commercially available sausages. Additionally, it conducted a comparative assessment of the distinctions among different samples by integrating sensory evaluation with textural and physicochemical parameters. The results of the GC-IMS analysis showed that a total of 65 volatile compounds were detected in the four samples, including 12 hydrocarbons, 11 alcohols, 10 ketones, 9 aldehydes, 12 esters, and 1 acids. Fingerprinting combined with principal component analysis (PCA) showed that the volatiles of different brands of sausages were significantly different (p < 0.05). The volatiles of S1 and S4 were more similar and significantly different from the other two samples (p < 0.05). Among them, there were 14 key volatile substances in the four samples, of which 3-hydroxy-2-butanone and diallyl sulfide were common to all four sausages. Combined textural and sensory evaluations revealed that smoked sausages exhibited superior characteristics in resilience, cohesiveness, springiness, gumminess, and chewiness. Additionally, smoked sausages were found to be more attractive in color, moderately spicy, and salty, while having a lower fat content. In conclusion, smoked sausages are preferred by consumers over flavored oil sausages.


Asunto(s)
Aromatizantes , Productos de la Carne , Compuestos Orgánicos Volátiles , Productos de la Carne/análisis , Aromatizantes/análisis , Compuestos Orgánicos Volátiles/análisis , Gusto , Cromatografía de Gases y Espectrometría de Masas , Análisis de Componente Principal , Humanos , Espectrometría de Movilidad Iónica/métodos
12.
Cancer Immunol Immunother ; 72(8): 2741-2755, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37119260

RESUMEN

Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+ T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.


Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Humanos , Epítopos de Linfocito T , Nitratos , Antígenos de Neoplasias , Neoplasias/tratamiento farmacológico , Linfocitos T Colaboradores-Inductores , Adyuvantes Inmunológicos , ADN , Inmunoterapia
13.
Opt Express ; 31(21): 33799-33814, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37859152

RESUMEN

A two-dimensional geometrical waveguide enables ultra-thin augmented reality (AR) near-eye display (NED) with wide field of view (FOV) and large exit-pupil diameter (EPD). A conventional design method can efficiently design waveguides that meet the requirements, but is unable to fully utilize the potential display performance of the waveguide. A forward-ray-tracing waveguide design method with maximum FOV analysis is proposed, enabling two-dimensional geometrical waveguides to achieve their maximum FOV while maintaining minimum dimensions. Finally, the designed stray-light-suppressed waveguide NED has a thickness of 1.7 mm, a FOV of 50.00°H × 29.92°V, and an eye-box of 12 mm × 12 mm at an eye-relief of 18 mm.

14.
Diabetes Metab Res Rev ; 39(7): e3679, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37337761

RESUMEN

AIMS: Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is scarce. The present multi-centre study sought to investigate these associations based on objective quantifications. MATERIALS AND METHODS: Information on DPN-related symptoms, signs, all diabetic microvascular complications, and nerve conduction abilities (quantified by nerve conduction amplitude and velocity, F-wave minimum latency (FML) of peripheral nerves) were collected from a derivation cohort of 1192 patients with type 2 diabetes (T2D). Correlation, regression analysis, and restricted cubic splines (RCS) were used to explore linear and non-linear relationships between vitamin D and DPN, which were validated in an external cohort of 223 patients. RESULTS: Patients with DPN showed lower levels of vitamin D than those without DPN; patients with vitamin D deficiency (<30 nmol/L) tended to suffer more DPN-related neurological deficits (paraesthesia, prickling, abnormal temperature, ankle hyporeflexia, and distal pall hypoesthesia correlating with MNSI-exam score (Y = -0.005306X + 2.105, P = 0.048). Worse nerve conduction abilities (decreased motor nerve amplitude, sensory nerve amplitude, motor nerve velocity, and increased FML) were also observed in these patients. Vitamin D had a significant threshold association with DPN (adjusted OR = 4.136, P = 0.003; RCS P for non-linearity = 0.003) and correlates with other microvascular complications (diabetic retinopathy and diabetic nephropathy). CONCLUSIONS: Vitamin D is associated with the conduction ability of peripheral nerves and may have a nerve- and threshold-selective relationship with the prevalence and severity of DPN among patients with T2D.


Asunto(s)
Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Deficiencia de Vitamina D , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Vitamina D , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/complicaciones , Pueblos del Este de Asia , Fluorometolona , Estudios de Conducción Nerviosa , Conducción Nerviosa/fisiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología
15.
BMC Cancer ; 23(1): 1131, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37990304

RESUMEN

Anaplastic thyroid carcinoma (ATC) was a rare malignancy featured with the weak immunotherapeutic response. So far, disorders of immunogenic cell death genes (ICDGs) were identified as the driving factors in cancer progression, while their roles in ATC remained poorly clear. Datasets analysis identified that most ICDGs were high expressed in ATC, while DE-ICDGs were located in module c1_112, which was mainly enriched in Toll-like receptor signalings. Subsequently, the ICD score was established to classify ATC samples into the high and low ICD score groups, and function analysis indicated that high ICD score was associated with the immune characteristics. The high ICD score group had higher proportions of specific immune and stromal cells, as well as increased expression of immune checkpoints. Additionally, TLR4, ENTPD1, LY96, CASP1 and PDIA3 were identified as the dynamic signature in the malignant progression of ATC. Notably, TLR4 was significantly upregulated in ATC tissues, associated with poor prognosis. Silence of TLR4 inhibited the proliferation, metastasis and clone formation of ATC cells. Eventually, silence of TLR4 synergistically enhanced paclitaxel-induced proliferation inhibition, apoptosis, CALR exposure and release of ATP. Our findings highlighted that the aberrant expression of TLR4 drove the malignant progression of ATC, which contributed to our understanding of the roles of ICDGs in ATC.


Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/patología , Receptor Toll-Like 4/genética , Muerte Celular Inmunogénica , Paclitaxel/uso terapéutico , Neoplasias de la Tiroides/patología , Línea Celular Tumoral
16.
Anticancer Drugs ; 34(9): 1058-1064, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37265026

RESUMEN

Rearranged during transfection ( RET ) fusions and epidermal growth factor receptor ( EGFR ) mutations are potent oncogenic drivers in patients with nonsmall cell lung cancer (NSCLC), but rarely co-exist. Concurrent RET/EGFR mutations have been reported in patients with NSCLC who develop resistance to EGFR tyrosine kinase inhibitors but are even less frequent in treatment-naïve patients. Consequently, there is no standard treatment for RET/EGFR -mutated NSCLC. We report a case of RET/EGFR mutant NSCLC successfully treated with the oral, potent, highly selective RET inhibitor selpercatinib (160 mg daily for 28-day cycles) in an ongoing phase II study in Chinese patients with NSCLC (LIBRETTO-321). The patient, a female nonsmoker, was diagnosed with de-novo left lung adenocarcinoma with neuroendocrine differentiation, and a RET fusion was detected by next-generation sequencing testing. The patient had two tumors in the pleura, a third in the subcarinal lymph node, and a nontarget tumor in the pleura. Pleural biopsy analysis confirmed a RET fusion KIF5B (K15;R12) and an EGFR exon 19 deletion. The patient achieved a partial response (PR) with selpercatinib (absence of target tumors in pleura and reduction in the size of lymph node tumor). The PR persisted for 14.7 months, with disease progression in the nontarget lesion in the pleura and a new lesion in the liver (the PR had persisted), resulting in the discontinuation of selpercatinib. The only notable adverse event was grade 3 elevated transaminase, that was effectively managed by dose reduction. These data may support the use of selpercatinib in patients with RET/EGFR co-mutated NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Femenino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Pueblos del Este de Asia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas c-ret/metabolismo , Ensayos Clínicos Fase II como Asunto
17.
Crit Rev Food Sci Nutr ; : 1-20, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37078096

RESUMEN

This work summarizes the application of gas fumigation technology in postharvest fruit quality management and related biochemical mechanisms in recent years. Gas fumigants mainly include SO2, ClO2, ozone, NO, CO, 1-MCP, essential oils, H2S and ethanol. This work indicated that gas fumigation preservatives can effectively improve postharvest fruit quality, which is mainly manifested in delaying senescence, inhibiting browning, controlling disease and alleviating chilling injury. Gas preservatives are mainly involved in postharvest fruit quality control in the roles of antifungal agent, anti-browning agent, redox agent, ethylene inhibitors, elicitor and pesticide remover. Different gas preservatives have different roles, but most of them have multiple roles at the same time in postharvest fruit quality management. In addition, the role of some gas preservatives with direct antifungal activity in the control of postharvest fruit diseases can also activate defense systems to improve fruit resistance. It should be noted that some gas fumigation treatments with slow-release effects have been developed recently, which may allow gas fumigation gases to perform better. Moreover, some gas fumigants can cause irrational side effects on the fruit and some combined treatments need to be found to counteract such side effects.

18.
Crit Rev Food Sci Nutr ; : 1-21, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37702799

RESUMEN

Probiotics (PRO) have been recognized for their significant role in promoting human health, particularly in relation to colon-related diseases. The effective delivery of PRO to the colon is a fascinating area of research. Among various delivery materials, carbohydrates have shown great potential as colon-targeted delivery (CTD) carriers for PRO. This review explores the connection between probiotics and colonic diseases, delving into their underlying mechanisms of action. Furthermore, it discusses current strategies for the targeted delivery of active substances to the colon. Unlike other reviews, this work specifically focuses on the utilization of carbohydrates, such as alginate, chitosan, pectin, and other carbohydrates, for probiotic colon-targeted delivery applications. Carbohydrates can undergo hydrolysis at the colonic site, allowing their oligosaccharides to function as prebiotics or as direct functional polysaccharides with beneficial effects. Furthermore, the development of multilayer self-assembled coatings using different carbohydrates enables the creation of enhanced delivery systems. Additionally, chemical modifications of carbohydrates, such as for adhesion and sensitivity, can be implemented to achieve more customized delivery of PRO.

19.
Crit Rev Food Sci Nutr ; 63(2): 288-301, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34229564

RESUMEN

As a bioactive extract from tea leaves, tea polyphenols (TP) are safe and natural. Its excellent antioxidant and antibacterial properties are increasingly regarded as a good additive for improving degradable food packaging film properties. This article comprehensively reviewed the functional properties of active films containing TP developed recently. The effects of TP addition to enhancing active food packaging films' performance, including thickness, water sensitivity, barrier properties, color, mechanical properties, antioxidant, antibacterial, and intelligent discoloration properties, were discussed. Besides, the practical applications in food preservation of active films containing TP are also discussed. This work concluded that the addition of TP could impart antioxidant and antibacterial properties to active packaging films and act as a crosslinking agent to improve other physical and chemical properties of the film, such as mechanical and barrier properties. However, the effect of TP on specific properties of the active packaging film is complex, and the appropriate TP concentration needs to be selected according to the type of film matrix and the interaction between the components. Notably, the addition of TP improved the efficiency of the active packaging film in food preservation applications, which accelerates the process of replacing the traditional plastic-based food packaging with active packaging film.


Asunto(s)
Embalaje de Alimentos , Polifenoles
20.
Crit Rev Food Sci Nutr ; : 1-23, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38063335

RESUMEN

For years, researchers have been tirelessly searching for efficient postharvest preservatives to ensure a sustainable and healthy supply chain of fresh fruits and vegetables. However, the effectiveness of preservatives is significantly influenced by delivery methods employed for preservatives. This work centers on delivery methods of diverse preservatives. It delves into the mechanisms of penetration and internalization that facilitate preservatives diffusion into fruits and vegetables. Furthermore, the study comprehensively reviews various delivery methods and their impact on postharvest quality of these fresh food. Methods include liquid surface impregnation (soaking, vacuum infiltration, spraying) and gaseous fumigation. Additionally, unconventional delivery measures, such as fruit stem delivery, microbubble, and edible coating, are discussed in detail for the first time. It is expected that our work will provide inspiration for future development in academia, industry, and supervision.Through a comprehensive review on preservative delivery methods in fruits and vegetables preservation, it becomes evident that majority of existing studies concentrate on the development and mechanisms of preservatives. However, a notable gap lies in comparative analysis of different delivery methods, despite the direct impact of delivery methods on preservation outcomes. Additionally, emerging delivery techniques have displayed promising potential in enhancing delivery efficiency and likewise preservation effectiveness.


Preservative delivery methods (soaking, vacuum infiltration, spraying, fumigation) directly impact their effectiveness.Delivery efficiency is linked to fruit epidermis, including cuticle, intercellular spaces, and stomata.Research uses varied delivery methods, concentrations, and times for preserving different fruits.Promising preservative delivery methods: microbubble, fruit stem delivery, and edible coating.

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