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1.
Entropy (Basel) ; 26(10)2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39451940

RESUMEN

The rapid developments of 5G and B5G networks have posed higher demands on retransmission in certain scenarios. This article reviews classical finite-length coding performance prediction formulas and proposes rate prediction formulas for coded modulation retransmission scenarios. Specifically, we demonstrate that a recently proposed model for correcting these prediction formulas also exhibits high accuracy in coded modulation retransmissions. To enhance the generality of this model, we introduce a range variable Pfinal to unify the predictions with different SNRs. Finally, based on simulation results, the article puts forth recommendations specific to retransmission with a high spectral efficiency.

2.
Aging Cell ; : e14374, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39411913

RESUMEN

Alzheimer's diseases (AD) patients suffer from more serious bone loss than cognitively normal subjects at the same age. Type H blood vessels were tightly associated with bone homeostasis. However, few studies have concentrated on bone vascular alteration and its role in AD-related bone loss. In this study, APP/PS1 mice (4- and 8-month-old) and age-matched wild-type mice were used to assess the bone vascular alteration and its role in AD-related bone loss. Transmission electron microscopy, immunofluorescence staining and iGPS 1.0 software database were utilized to investigate the molecular mechanism. Mitochondrial division inhibitor (Mdivi-1) and GSK-3ß inhibitor (LiCl) were used to rescue type H blood vessels injury and verify the molecular mechanism. Our results revealed that APP/PS1 mice exhibited more serious bone blood vessels injury and bone loss during ageing. The bone blood vessel injury, especially in type H blood vessels, was accompanied by impaired vascularized osteogenesis in APP/PS1 mice. Further exploration indicated that beta-amyloid (Aß) promoted the apoptosis of vascular endothelial cells (ECs) and resulted in type H blood vessels injury. Mechanistically, Aß-induced excessive mitochondrial fission was found to be essential for the apoptosis of ECs. GSK-3ß was identified as a key regulatory target of Aß-induced excessive mitochondrial fission and bone loss. The findings delineated that Aß-induced excessive mitochondrial fission drives type H blood vessels injury, leading to aggravate bone loss in APP/PS1 mice and GSK-3ß inhibitor emerges as a potential therapeutic strategy.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39392197

RESUMEN

BACKGROUND AND AIM: This study aimed to investigate the relationship between advanced lung cancer inflammation index (ALI) and non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF). METHODS: A total of 5642 individuals from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020 were examined. Limited cubic spline regression model, and weighted logistic regression were employed to determine if ALI levels were related to the prevalence of NAFLD and AF. Additionally, a mediating analysis was conducted to investigate the role of lipid biomarkers, such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), in the effects of ALI on the prevalence of NAFLD and AF. RESULTS: After adjusting for potential confounders, a significant positive association was found between ALI with NAFLD and AF prevalence. Compared with those in ALI Tertile 1, participants in Tertile 3 had higher odds of NAFLD prevalence (odds ratio [OR]: 3.16; 95% confidence interval [CI]: 2.52-3.97) and AF (OR: 3.17; 95% CI: 2.30-4.36). Participants in both Tertile 2 and Tertile 3 had lower odds of developing AF (P for trend = 0.005). Moreover, we discovered a nonlinear association between ALI and NAFLD. An inflection point of 74.25 for NAFLD was identified through a two-segment linear regression model. Moreover, TC and HDL-C levels mediated the association between ALI and NAFLD by 10.2% and 4.2%, respectively (both P < 0.001). CONCLUSION: Our findings suggest that higher ALI levels are positively associated with an increased prevalence of NAFLD and AF, partly mediated by lipid biomarkers.

4.
Plants (Basel) ; 13(17)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39273964

RESUMEN

Using Panax japonicus as research material, callus induction and culture were carried out, and high-yielding cell lines were screened to establish a suspension culture system that promotes callus growth and the accumulation of the "total saponins" (total content of triterpenoid glycosides or ginsenosides). Using the root as an explant, the medium for callus induction and proliferation was optimized by adjusting culture conditions (initial inoculation amount, carbon source, shaking speed, hormone concentration, culture time) and a high-yielding cell line with efficient proliferation and high total saponins content was screened out. The conditions of suspension culture were refined to find out the most suitable conditions for the suspension culture of callus, and finally, the suspension culture system was established. We found that the lowest (5%) contamination rate was achieved by disinfecting the fresh roots with 75% alcohol for 60 s, followed by soaking in 10% NaClO for 15 min. The highest induction rate (88.17%) of callus was obtained using the medium MS + 16.11 µmol·L-1 NAA + 13.32 µmol·L-1 6-BA + 30.0 g·L-1 sucrose + 7.5 g·L-1 agar. The callus was loose when the callus subcultured on the proliferation medium (MS + 5.37 µmol·L-1 NAA + 13.32 µmol·L-1 6-BA + 30.0 g·L-1 sucrose + 3.8 g·L-1 gellan gum) for 21 days. The callus growth was cultured in a liquid growth medium (MS + 5.37 µmol·L-1 NAA + 13.32 µmol·L-1 6-BA + 30.0 g·L-1 sucrose) with an initial inoculation amount of 40 g·L-1, a shaking speed of 110 r/min and darkness. Cell growth was fastest with a culture period of 21 days. We replaced the growth medium with the production medium (MS + 5.37 µmol·L-1 NAA + 13.32 µmol·L-1 6-BA + 30.0 g·L-1 glucose) for maximum accumulation of total saponins. [Conclusion] A callus induction and suspension culture system for the root of P. japonicus was established. In this way, we can promote the accumulation of total saponins in callus cells and provide a basis for large-scale cell culture and industrial production of medicinal total saponins.

5.
Cancer Res ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264725

RESUMEN

Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSCs) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of pre-leukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded by a RUNX1::RUNX1T1 fusion gene, is capable of generating pre-leukemic clones, here we used a conditional Runx1::Runx1t1 knock-in mouse model to evaluate pre-leukemic cell metabolism. AML1-ETO expression resulted in impaired hematopoietic reconstitution and increased self-renewal ability. Oxidative phosphorylation and glycolysis decreased significantly in these pre-leukemic cells accompanied by increased HSC quiescence and reduced cell cycling. Furthermore, HSCs expressing AML1-ETO exhibited an increased requirement for fatty acids through metabolic flux. Dietary lipid deprivation or loss of the fatty acid transporter FATP3 by targeted deletion using CRISPR/Cas9 partially restored differentiation. These findings reveal the unique metabolic profile of pre-leukemic cells and propose FATP3 as a potential target for disrupting leukemogenesis.

6.
Transl Cancer Res ; 13(8): 4420-4440, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39262480

RESUMEN

Background: Immunogenic cell death (ICD) is a functionally specialized form of apoptosis induced by endoplasmic reticulum (ER) stress and is associated with a variety of cancers, including gastric cancer (GC). In recent years, long non-coding RNAs (lncRNAs) have been shown to be important mediators in the regulation of ICD. However, the specific role and prognostic value of ICD-related lncRNAs in GC remain unclear. This study aims to develop an ICD-related lncRNAs signature for prognostic risk assessment in GC. Methods: The ICD-related lncRNAs signature (ICDlncSig) of GC was constructed by univariate Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression model and multivariate Cox regression analysis, and the signature was correlated with immune infiltration. The potential response of GC patients to immunotherapy was predicted by the tumor immune dysfunction and rejection (TIDE) algorithm. In vitro functional experiments were conducted to assess the impact of lncRNAs on the proliferation, migration, and invasion capabilities of GC cells. Results: We constructed a novel ICDlncSig and found that this signature could be used as a prognostic risk model to predict survival of GC patients by validating it in the training cohort, testing cohort and entire cohort. The robust predictive power of the signature was demonstrated by building a Nomogram based on ICDlncSig scores and clinical characteristics. Furthermore, immune cell subpopulations, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. The in vitro functional experiments revealed that AP002954.1 and AP000695.1 can promote the proliferation, migration, and invasion of GC cells. Conclusions: In conclusion, our ICDlncSig model has significant predictive value for the prognosis of GC patients and may provide clinical guidance for individualized immunotherapy.

7.
Sci Rep ; 14(1): 19674, 2024 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-39181925

RESUMEN

Sleep quality is crucial for the personal well-being of healthcare professionals and the health outcomes of their patients. This study aims to explore the relationship between psychological resilience (PR), perceived social support (PSS), psychological distress (comprising anxiety,depression,and stress), and sleep quality. It also examines whether PSS and psychological distress function as chain mediators between PR and sleep quality. A cross-sectional online survey was conducted using a convenient sampling method, with 454 participants included. The survey instruments included the Connor and Davidson Resilience Scale, the Perceived Social Support Scale, the 21-item Depression Anxiety Stress Scale, and the Pittsburgh Sleep Quality Index. Structural equation modeling revealed that PR significantly predicted sleep quality of Chinese medical staff. Psychological distress was identified as a mediating factor between PR and sleep quality. However, PSS did not directly mediate the relationship between PR and sleep quality. Instead, PSS and psychological distress were found to play a chain mediating role in the relationship between PR and sleep quality. This study provides new insights into the impact of PR on sleep quality, highlights the importance of PSS and psychological distress, and suggests practical implications for enhancing sleep quality among medical staff.


Asunto(s)
Distrés Psicológico , Resiliencia Psicológica , Calidad del Sueño , Apoyo Social , Humanos , Femenino , Masculino , Adulto , Estudios Transversales , Persona de Mediana Edad , China/epidemiología , Encuestas y Cuestionarios , Cuerpo Médico/psicología , Estrés Psicológico/psicología , Depresión/psicología , Depresión/epidemiología , Adulto Joven , Ansiedad/psicología , Pueblos del Este de Asia
8.
China CDC Wkly ; 6(26): 619-623, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38966310

RESUMEN

What is already known about this topic?: Since May 2022, a global outbreak of mpox has emerged in more than 100 non-endemic countries. As of December 2023, over 90,000 cases had been reported. The outbreak has predominantly affected men who have sex with men (MSM), with sexual contact identified as the principal mode of transmission. What is added by this report?: Since June 2023, China has faced an occurrence of mpox, predominantly affecting the MSM population. Approximately 90% of those affected reported engaging in homosexual behavior within 21 days prior to symptom onset, a trend that aligns with the global outbreak pattern. The prompt identification of cases, diligent tracing of close contacts, and the implementation of appropriate management strategies have successfully mitigated the spread of mpox virus in China. What are the implications for public health practice?: We propose that mpox is transmitted locally within China. Drawing from our experiences in controlling the virus spread, it is crucial to investigate and formulate effective surveillance and educational strategies. Importantly, we must encourage high-risk populations to promptly seek medical care upon the onset of symptoms.

9.
Adv Sci (Weinh) ; 11(30): e2308764, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38888508

RESUMEN

The mechanism research of skin wrinkles, conducted on volunteers underwent high-intensity desk work and mice subjected to partial sleep deprivation, revealed a significant reduction in dermal thickness associated with the presence of wrinkles. This can be attributed to the activation of facial nerves in a state of hysteria due to an abnormally elevated interaction between SNAP25 and RAB3A proteins involved in the synaptic vesicle cycle (SVC). Facilitated by AI-assisted structural design, a refined peptide called RSIpep is developed to modulate this interaction and normalize SVC. Drawing inspiration from prions, which possess the ability to protect themselves against proteolysis and invade neighboring nerve cells through macropinocytosis, RSIpep is engineered to demonstrate a GSH-responsive reversible self-assembly into a prion-like supermolecule (RSIprion). RSIprion showcases protease resistance, micropinocytosis-dependent cellular internalization, and low adhesion with constituent molecules in the cuticle, thereby endowing it with the transdermic absorption and subsequent biofunction in redressing the frenzied SVC. As a facial mud mask, it effectively reduces periorbital and perinasal wrinkles in the human face. Collectively, RSIprion not only presents a clinical potential as an anti-wrinkle prion-like supermolecule, but also exemplifies a reproducible instance of bionic strategy-guided drug development that bestows transdermal ability upon the pharmaceutical molecule.


Asunto(s)
Priones , Envejecimiento de la Piel , Ratones , Animales , Humanos , Envejecimiento de la Piel/efectos de los fármacos , Priones/metabolismo , Proteína de Unión al GTP rab3A/metabolismo , Administración Cutánea , Cara , Modelos Animales de Enfermedad , Adulto , Piel/metabolismo , Piel/efectos de los fármacos , Masculino , Femenino
10.
Opt Express ; 32(10): 16879-16890, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858884

RESUMEN

In this paper, a polarization-insensitive high transmittance bandpass filter with low radar cross section (RCS) in both S- and X-band is proposed. This is the first study to use the partition layout loading approach for conformal structures with transmissive windows, reducing the operating band RCS. Curved structures have stronger radiation at a smaller angle to the incident wave, and that is how their scattering differs from uniform scattering from flat structures. The structure is divided by analyzing the radiative contribution of different regions. The surface was discussed in regions according to surface angles, and a new partition layout loading method was used to suppress the side currents and decreased backward scattering, achieving a backward RCS reduction of more than 10 dB at 4-8 GHz (66.7%). The bandpass layer operating at 6.9 GHz is designed through equivalent circuit theory. In combination with the lossy layer, absorption above 0.8 at 3.7-5.6 GHz and 9.1-12.5 GHz was achieved. Further, the structure was fashioned into a curved surface with varying curvature, demonstrating its effective absorption and transmission properties across different curvatures. A 15 × 15 cell structure was designed and fabricated, and there was good agreement between the test results and simulation results. The proposed structure has important applications in radomes, conformal structures, and electromagnetic shielding.

11.
Sci Rep ; 14(1): 13071, 2024 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844544

RESUMEN

Knowledge, Attitude, and Practice (KAP) survey, as an effective measure tool, is of practical significance for identifying the susceptible population in high-incidence regions of tuberculosis (TB). We aim to identify the health education targeted susceptible population of TB and discuss the acting pathway of KAP in Ningxia. A multistage random sampling method was used to conduct a face-to-face questionnaire survey for residents. The latent class analysis (LCA) model was used to classify susceptible populations of TB, and the structural equation modeling (SEM) model was also employed to investigate the interaction mechanisms of KAP (mediation analysis). We further applied the ordered logistic regression model to explore the associated factors. A total of 973 residents were enrolled, 70.6% were male, aged from 16 to 89. The LCA analysis demonstrated that 3 categories of susceptible populations of TB ("overall good", "positive attitude" and "overall poor") have optimal goodness of fit (BIC = 7889.5, Entropy = 0.923). SEM model indicated that the attitude plays a significant mediation effect from knowledge to practice toward TB (an indirect effect of 0.038, and a direct effect of 0.138). The ordered logistic regression results found that age, sex, marital status, education level, occupation, family income, self-perceived health status, having a family member or friend with TB, and knowing the DOTS strategy were significantly associated with classifications of KAP level towards TB. Based on the LCA model, we accurately classified the susceptible population of TB into 3 groups with different degrees of KAP. We found that TB attitude plays a mediating role between knowledge and practice. Therefore, we should pay more attention and carry out targeted health education in the community to these populations with overall poor KAP towards TB, and develop effective strategies and measures to realize the End TB Plan.


Asunto(s)
Educación en Salud , Conocimientos, Actitudes y Práctica en Salud , Tuberculosis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , China/epidemiología , Adolescente , Anciano , Tuberculosis/epidemiología , Adulto Joven , Anciano de 80 o más Años , Encuestas y Cuestionarios
12.
ACS Appl Mater Interfaces ; 16(27): 35716-35722, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38917377

RESUMEN

Low detectability and camouflage skills in the electromagnetic wave and light frequency range provide survival advantages for natural creatures and are essential for understanding the operational principles of the biosphere. Taking inspiration from natural mutualistic symbiosis, this paper proposes a symbiotic electromagnetic shadow camouflage mechanism based on a superdispersive surface, aiming to investigate its impact on the observability of specific objects. The design and experimental results indicate that the symbiotic shadow dihedral can significantly reduce overall scattering quantity, which reaches at least 10 dB shrink in the 12-18 GHz frequency range compared to the contrast object. Unlike known camouflage methods, the electromagnetic shadow technology shrinks the overall scattering without any coating and shield metal target while probably offering extensive functional design freedom for the concealed object, creature, or equipment. This also provides a hint to explore symbiosis-related camouflage phenomena in nature.

13.
Inorg Chem ; 63(27): 12604-12614, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38918078

RESUMEN

The development of bifunctional electrocatalysts with excellent performance in both the hydrogen evolution reaction (HER) and sulfide oxidation reaction (SOR) remains a formidable challenge. Herein, we experimentally synthesize a NiO/RuO2 p-n heterojunction nanofoam that exhibits highly desirable electrocatalytic properties for both the HER and the SOR. We further design an electrolytic cell by pairing alkaline HER with SOR utilizing the NiO/RuO2 heterojunction nanofoam as both the anode and the cathode, which demands a low applied voltage of 0.846 V to achieve a current density of 10 mA cm-2. Density functional theory calculations confirm that the formation of the NiO/RuO2 p-n heterojunction nanofoam effectively regulates the electronic structure, thereby boosting the electrocatalytic performances for both HER and SOR. This work not only provides a novel strategy to prepare an efficient and stable nanofoam electrocatalyst for hydrogen production but also highlights the potential application of oxide heterojunction electrocatalysts in treating sulfur-containing waste liquid.

15.
J Colloid Interface Sci ; 668: 634-645, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38696991

RESUMEN

Solid polymer electrolytes (SPEs) have been considered the most promising separators for all-solid-state lithium metal batteries (ASSLMBs) due to their ease of processing and low cost. However, the practical applications of SPEs in ASSLMBs are limited by their low ionic conductivities and mechanical strength. Herein, we developed a three-dimensional (3D) interconnected MXene (Ti3C2Tx) network and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) particles synergistically reinforced polyethylene oxide (PEO)-based SPE, where the association of Li+ with ether-oxygen in PEO could be significantly weakened through the Lewis acid-base interactions between the electron-absorbing group (Ti-F, -O-) of Ti3C2Tx and Li+. Besides, the TFSI- in lithium salts could be immobilized by hydrogen bonds from the Ti-OH of Ti3C2Tx. The 3D interconnected Ti3C2Tx network not only alleviated the agglomeration of inorganic fillers (LLZTO), but also improved the mechanical strength of composite solid electrolyte (CSE). Consequently, the assembled Li||CSE||Li symmetric battery showed excellent cycling stability at 35 ℃ (stable cycling over 3000 h at 0.1 mA cm-2, 0.1 mAh cm-2) and -2 ℃ (stable cycling over 2500 h at 0.05 mA cm-2, 0.05 mAh cm-2). Impressively, the LiFePO4||CSE||Li battery showed a high discharge capacity of 145.3 mAh/g at 0.3 C after 300 cycles at 35 ℃. This rational structural design provided a new strategy for the preparation of high-performance solid-state electrolytes for lithium metal batteries.

16.
Materials (Basel) ; 17(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38730831

RESUMEN

Considering the different structural strength requirements of different parts of fiberglass yachts, carbon fiber/glass fiber hybrid reinforcement can be applied to the skins of sandwich panels in special areas. This paper designs and prepares 12 foam sandwich panel samples composed of pure carbon fiber, a carbon fiber/glass fiber hybrid, pure glass fiber skin, and PVC and SAN foam sandwich, with reference to the layup structure of the outer panel of a fiberglass yacht. Through a comparative analysis of low-speed impact experiments, edge compression experiments, and short beam three-point bending experiments, we seek the optimal carbon fiber/glass fiber hybrid layup design scheme for local structures to guide production. The results show that a reasonable hybrid carbon fiber layup in fiberglass skin can effectively reduce the low-speed impact damage of the sandwich structure, reduce edge compression damage, and improve the bending and compression resistance of sandwich structure. The impact resistance, compression resistance, and shear resistance of the SAN sandwich structure are stronger than the PVC sandwich structure. The carbon fiber/glass fiber hybrid SAN foam sandwich structure can be used for the local structural reinforcement of special parts such as the bow, side, and main deck of fiberglass yachts.

17.
Trends Biotechnol ; 42(9): 1097-1111, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38604879

RESUMEN

Molecular imprints, which are crosslinked architectures containing specific molecular recognition cavities for targeting compounds, have recently transitioned from in vitro diagnosis to in vivo treatment. In current application scenarios, it has become an important topic to create new biomolecular recognition pathways through molecular imprinting, thereby inhibiting the pathogenesis and regulating the development of diseases. This review starts with a pathological analysis, mainly focusing on the corresponding artificial enzymes, enzyme inhibitors and antibody mimics with enhanced functions that are created by molecular imprinting strategies. Recent advances are highlighted in the use of molecular imprints as tailor-made nanomedicines for the prevention of three major diseases: metabolic syndrome, cancer, and bacterial/viral infections.


Asunto(s)
Impresión Molecular , Humanos , Impresión Molecular/métodos , Nanomedicina/métodos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales
18.
BMC Infect Dis ; 24(1): 413, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641791

RESUMEN

Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron.Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023).


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Vacunas de Subunidad , Adolescente , Niño , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Inmunogenicidad Vacunal , SARS-CoV-2 , Vacunas de Productos Inactivados/efectos adversos , Preescolar
19.
Front Endocrinol (Lausanne) ; 15: 1340625, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38532900

RESUMEN

The intervertebral disc is not isolated from other tissues. Recently, abundant research has linked intervertebral disc homeostasis and degeneration to various systemic diseases, including obesity, metabolic syndrome, and diabetes. Organokines are a group of diverse factors named for the tissue of origin, including adipokines, osteokines, myokines, cardiokines, gastrointestinal hormones, and hepatokines. Through endocrine, paracrine, and autocrine mechanisms, organokines modulate energy homeostasis, oxidative stress, and metabolic balance in various tissues to mediate cross-organ communication. These molecules are involved in the regulation of cellular behavior, inflammation, and matrix metabolism under physiological and pathological conditions. In this review, we aimed to summarize the impact of organokines on disc homeostasis and degeneration and the underlying signaling mechanism. We focused on the regulatory mechanisms of organokines to provide a basis for the development of early diagnostic and therapeutic strategies for disc degeneration.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Humanos , Adipoquinas/metabolismo , Obesidad/metabolismo , Homeostasis
20.
Sci Rep ; 14(1): 6568, 2024 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-38503887

RESUMEN

While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan-Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3'-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy.


Asunto(s)
MicroARNs , Neoplasias Gástricas , Animales , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica , Luciferasas/metabolismo , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Gástricas/patología
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