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1.
Int J Nanomedicine ; 19: 9943-9959, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355653

RESUMEN

Introduction: Alzheimer's disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy. Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aß1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level. Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H2O2-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-ß deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation. Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.


Asunto(s)
Enfermedad de Alzheimer , Barrera Hematoencefálica , Cerio , Curcumina , Estrés Oxidativo , Circonio , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Células PC12 , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Circonio/química , Circonio/farmacocinética , Ratones , Ratas , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacología , Curcumina/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Cerio/química , Cerio/farmacocinética , Cerio/farmacología , Cerio/administración & dosificación , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/química , Distribución Tisular , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/química , Modelos Animales de Enfermedad , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Estructuras Metalorgánicas/farmacología , Masculino , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo
2.
Sci China Life Sci ; 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39428428

RESUMEN

Despite substantial advancements in modern medicine, the management of hypertension remains a major challenge. Stem cell-based therapies have recently demonstrated remarkable efficacy in treating cardiovascular diseases, including hypertension. However, the antihypertensive mechanism of mesenchymal stem cells (MSCs) has not been extensively explored. This study aimed to investigate the role of injected MSCs in regulating blood pressure homeostasis. Our previous study demonstrated that human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) are functional and homogeneous sources for MSC-based therapy. After the injection of hiPSC-MSCs, a significant reduction in blood pressure and end target organ inflammation were observed in spontaneously hypertensive rats (SHRs). Cell tracking assays demonstrated that the injected hiPSC-MSCs accumulated in the spleens of the SHRs. The injected hiPSC-MSCs accumulated adjacent to the splenic nerve, potentially contributing to the antihypertensive effects. Furthermore, the hiPSC-MSCs released abundant glutamate, which acts as a neuromodulator to activate the splenic sympathetic nerve. After inhibition of glutamate synthesis by siRNA, the ability of hiPSC-MSCs to activate sympathetic nerves was significantly diminished. In addition, the antihypertensive effects of hiPSC-MSCs were eliminated after splenic nerve denervation (SND), underscoring the critical role of the splenic nerve. Moreover, activation of the splenic nerve resulted in increased release of norepinephrine (NE), which increased the number of choline acetyltransferase-positive (ChAT+) cells in the spleen and peripheral blood. Consequently, the acetylcholine (ACh) produced by elevated ChAT+ cells could act as a vasodilator, lowering blood pressure and mitigating inflammation in end target organs. In summary, our findings indicate that hiPSC-MSCs effectively lower blood pressure in hypertension by influencing the splenic nerves and regulating ChAT+ cells. The connection between blood pressure regulation and the splenic nerve may offer new insights into the treatment of hypertension.

3.
Oncol Rep ; 52(6)2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39422059

RESUMEN

Bone metastasis (BM) is a common complication of cancer and contributes to a higher mortality rate in patients with cancer. The treatment of BM remains a significant challenge for oncologists worldwide. The colony­stimulating factor (CSF) has an important effect on the metastasis of multiple cancers. In vitro studies have shown that CSF acts as a cytokine, promoting the colony formation of hematopoietic cells by activating granulocytes and macrophages. Other studies have shown that CSF not only promotes cancer aggressiveness but also correlates with the development and prognosis of various types of cancer. In recent years, the effect of CSF on BM has been primarily investigated using cellular and animal models, with limited clinical studies available. The present review discussed the composition and function of CSF, as well as its role in the progression of BM across various types of cancer. The mechanisms by which osteoclast­ and osteoblast­mediated BM occur are comprehensively described. In addition, the mechanisms of action of emerging therapeutic agents are explored for their potential clinical applications. However, further clinical studies are required to validate these findings.


Asunto(s)
Neoplasias Óseas , Osteoclastos , Humanos , Neoplasias Óseas/secundario , Neoplasias Óseas/tratamiento farmacológico , Animales , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteoclastos/metabolismo , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/patología , Factores Estimulantes de Colonias/uso terapéutico , Pronóstico
5.
Appetite ; 203: 107694, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39341080

RESUMEN

The human brain works as a hierarchical organization that is a continuous axis spanning sensorimotor cortex to transmodal cortex (referring to cortex that integrates multimodal sensory information and participates in complex cognitive functions). Previous studies have demonstrated abnormalities in several specific networks that may account for their multiple behavioral deficits in patients with bulimia nervosa (BN), but whether and how the network hierarchical organization changes in BN remain unknown. This study aimed to investigate alterations of the hierarchy organization in BN network and their clinical relevance. Connectome gradient analyses were applied to depict the network hierarchy patterns of fifty-nine patients with BN and thirty-nine healthy controls (HCs). Then, we evaluated the network- and voxel-level gradient alterations of BN by comparing gradient values in each network and each voxel between patients with BN and HCs. Finally, the association between altered gradient values and clinical variables was explored. In the principal gradient, patients with BN exhibited reduced gradient values in dorsal attention network and increased gradient values in subcortical regions compared to HCs. In the secondary gradient, patients with BN showed decreased gradient values in ventral attention network and increased gradient values in limbic network. Regionally, the areas with altered principal or secondary gradient values in BN group were mainly located in transmodal networks, i.e., the default-mode and frontoparietal network. In BN group, the principal gradient values of right inferior frontal gyrus were negatively associated with external eating behavior. This study revealed the disordered network hierarchy patterns in patients with BN, which suggested a disturbance of brain information integration from attention network and subcortical regions to transmodal networks in these patients. These findings may provide insight into the neurobiological underpinnings of BN.

6.
Int J Mol Sci ; 25(18)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39337621

RESUMEN

The serine/threonine kinase PAK4 plays a crucial role in regulating cell proliferation, survival, migration, and invasion. Overexpression of PAK4 correlates with poor prognosis in some cancers. KPT-9274, a PAK4 inhibitor, significantly reduces the growth of triple-negative breast cancer cells and mammary tumors in mouse models, and it also inhibits the growth of several other types of cancer cells. Interestingly, although it was first identified as a PAK4 inhibitor, KPT-9274 was also found to inhibit the enzyme NAMPT (nicotinamide phosphoribosyltransferase), which is crucial for NAD (nicotinamide adenine dinucleotide) synthesis and vital for cellular energy and growth. These results made us question whether growth inhibition in response to KPT-9274 was due to PAK4 inhibition, NAMPT inhibition, or both. To address this, we tested several other PAK4 inhibitors that also inhibit cell growth, to determine whether they also inhibit NAMPT activity. Our findings confirm that multiple PAK4 inhibitors also inhibit NAMPT activity. This was assessed both in cell-free assays and in a breast cancer cell line. Molecular docking studies were also used to help us better understand the mechanism by which PAK4 inhibitors block PAK4 and NAMPT activity, and we identified specific residues on the PAK4 inhibitors that interact with NAMPT and PAK4. Our results suggest that PAK4 inhibitors may have a more complex mechanism of action than previously understood, necessitating further exploration of how they influence cancer cell growth.


Asunto(s)
Citocinas , Simulación del Acoplamiento Molecular , Nicotinamida Fosforribosiltransferasa , Quinasas p21 Activadas , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Nicotinamida Fosforribosiltransferasa/metabolismo , Quinasas p21 Activadas/antagonistas & inhibidores , Quinasas p21 Activadas/metabolismo , Humanos , Línea Celular Tumoral , Citocinas/metabolismo , Proliferación Celular/efectos de los fármacos , Acrilamidas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Femenino , Bencenoacetamidas/farmacología , Aminopiridinas
7.
Metabolism ; 160: 155994, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39117060

RESUMEN

BACKGROUND: Sarcopenia, characterized by progressive muscle mass and function loss, particularly affects the elderly, and leads to severe consequences such as falls and mortality. Despite its prevalence, targeted pharmacotherapies for sarcopenia are lacking. Utilizing large-sample genome-wide association studies (GWAS) data is crucial for cost-effective drug discovery. METHODS: Herein, we conducted four studies to understand the putative causal effects of genetic components on muscle mass and function. Study 1 employed a two-sample Mendelian randomization (MR) on 15,944 potential druggable genes, investigating their potential causality with muscle quantity and quality in a European population (N up to 461,089). Study 2 validated MR results through sensitivity analyses and colocalization analyses. Study 3 extended validation across other European cohorts, and study 4 conducted quantitative in vivo verification. RESULTS: MR analysis revealed significant causality between four genes (BLOC-1 related complex subunit 7, BORCS7; peptidase m20 domain containing 1, PM20D1; nuclear casein kinase and cyclin dependent kinase substrate 1, NUCKS1 and ubiquinol-cytochrome c reductase complex assembly factor 1, UQCC1) and muscle mass and function (p-values range 5.98 × 10-6 to 9.26 × 10-55). To be specific, BORCS7 and UQCC1 negatively regulated muscle quantity and quality, whereas enhancing PM20D1 and NUCKS1 expression showed promise in promoting muscle mass and function. Causal relationships remained robust across sensitivity analyses, with UQCC1 exhibiting notable colocalization effects (PP·H4 93.4 % to 95.8 %). Further validation and in vivo replication verified the potential causality between these genes and muscle mass as well as function. CONCLUSIONS: Our druggable genome-wide MR analysis identifies BORCS7, PM20D1, NUCKS1, and UQCC1 as causally associated with muscle mass and function. These findings offer insights into the genetic basis of sarcopenia, paving the way for these genes to become promising drug targets in mitigating this debilitating condition.


Asunto(s)
Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Sarcopenia , Humanos , Sarcopenia/genética , Masculino , Femenino , Anciano , Músculo Esquelético/metabolismo , Polimorfismo de Nucleótido Simple , Persona de Mediana Edad
8.
Sci Rep ; 14(1): 15509, 2024 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969683

RESUMEN

Polyploidization plays an important role in plant evolution and biodiversity. However, intraspecific polyploidy compared to interspecific polyploidy received less attention. Clintonia udensis (Liliaceae) possess diploid (2n = 2x = 14) and autotetraploid (2n = 4x = 28) cytotypes. In the Hualongshan Mountains, the autotetraploids grew on the northern slope, while the diploids grew on the southern slopes. The clonal growth characteristics and clonal architecture were measured and analyzed by field observations and morphological methods. The diversity level and differentiation patterns for two different cytotypes were investigated using SSR markers. The results showed that the clonal growth parameters, such as the bud numbers of each rhizome node and the ratio of rhizome branches in the autotetraploids were higher than those in the diploids. Both the diploids and autotetraploids appeared phalanx clonal architectures with short internodes between ramets. However, the ramets or genets of the diploids had a relatively scattered distribution, while those of the autotetraploids were relatively clumping. The diploids and autotetraploids all allocated more biomass to their vegetative growth. The diploids had a higher allocation to reproductive organs than that of autotetraploids, which indicated that the tetraploids invested more resources in clonal reproduction than diploids. The clone diversity and genetic diversity of the autotetraploids were higher than that of the diploids. Significant genetic differentiation between two different cytotypes was observed (P < 0.01). During establishment and evolution, C. udensis autotetraploids employed more clumping phalanx clonal architecture and exhibited more genetic variation than the diploids.


Asunto(s)
Diploidia , Variación Genética , Tetraploidía , China , Biodiversidad , Repeticiones de Microsatélite/genética
9.
Breast Cancer Res ; 26(1): 117, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39039568

RESUMEN

BACKGROUND: Diabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored. METHODS: tRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM. RESULTS: We identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation. CONCLUSIONS: Hyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM.


Asunto(s)
Neoplasias de la Mama , Regulación Neoplásica de la Expresión Génica , Glucólisis , Hiperglucemia , Humanos , Femenino , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Hiperglucemia/metabolismo , Hiperglucemia/genética , Ratones , Proliferación Celular , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Línea Celular Tumoral , Carcinogénesis/genética , Regulación hacia Abajo , Proteína Quinasa C/metabolismo , Proteína Quinasa C/genética , Regulación hacia Arriba , Pronóstico
10.
ACS Med Chem Lett ; 15(7): 1026-1031, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39015267

RESUMEN

Cystinuria, a rare genetic disorder, is characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of l-cystine and subsequent l-cystine crystallization in urine and stone formation in the urinary tract. Inhibition of l-cystine crystallization by l-cystine diamides such as LH708 (2) represents a promising new approach to prevent stone formation in patients with cystinuria. While 2 shows promising in vivo efficacy and a good safety profile in a Slc3a1-knockout mouse model of cystinuria, further structural modification of 2 led to the discovery of 8-l-cystinyl bis(1,8-diazaspiro[4.5]decane) (LH1753, 3) incorporating a bioisosteric spiro bicyclic diamine 1,8-diazaspiro[4.5]decane for the N-methylpiperazine terminal groups in 2 as a promising candidate with 3 being about 120× more potent than l-cystine dimethyl ester (CDME, 1) and about 2× more potent than 2 in inhibiting l-cystine crystallization. Furthermore, 3 demonstrated good oral bioavailability and in vivo efficacy in preventing l-cystine stone formation in the Slc3a1-knockout mouse model of cystinuria.

11.
Polymers (Basel) ; 16(13)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-39000766

RESUMEN

Using dodecyl acrylate as a raw material and 2-Cyanoprop-2-yl-dithiobenzoate as a chain transfer agent, poly(dodecyl acrylate) is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Using poly(dodecyl acrylate) as stabilizers, narrowly dispersed poly(ε-caprolactone) microspheres with particle sizes ranging from 0.5 to 1.5 µm are successfully synthesized by ring-opening dispersion polymerization. The effects of the molecular weight of poly(dodecyl acrylate), the volume proportion of mixed solvent (i.e., 1,4-dioxane/heptane), and the reaction temperature on the particle size and its distribution are investigated. With careful control of the synthesis condition, microspheres can be obtained with a particle size distribution of 1.09 (Dw/Dn). The average particle size of poly(ε-caprolactone) microspheres decreased with the increase in the molecular weight of poly(dodecyl acrylate) and increased with the increase in the relative content of 1,4-dioxane. The uniformity of microspheres decreased with the increase in the polymerization temperature.

12.
J Adv Res ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960277

RESUMEN

INTRODUCTION: Gene exchange between viruses and hosts plays an important role in driving virus-host coevolution, enabling adaptation of both viruses and hosts to environmental changes. However, the mechanisms and functional significance of virus-host gene exchanges over long-term scales remain largely unexplored. OBJECTIVE: The present study aimed to gain insights into the role of viruses in virus-host interactions and coevolution by monitoring virome dynamics along a millennium-long land reclamation chronosequence. METHODS: We collected 24 soil samples from 8 stages of a millennium-long land reclamation chronosequence, including non-reclamation, and reclamation periods of 10, 50, 100, 300, 500, 700, and 1000 years. We characterized their metagenomes, and identified DNA viruses within these metagenomes. RESULTS: Our findings reveal a significant shift in viral community composition after 50 years of land reclamation, but soil viral diversity reached a stable phase approximately 300 years after the initial reclamation. Analysis of the virus-host network showed a scale-free degree distribution and a reduction in complexity over time, with generalist viruses emerging as key facilitators of horizontal gene transfer. CONCLUSION: These findings highlight the integral role of viruses, especially generalist types, in mediating gene exchanges between viruses and hosts, thereby influencing the coevolutionary dynamics in soil ecosystems over significant timescales. This study offers novel insights into long-term virus-host interactions, showing how the virome responds to environmental changes, driving shifts in various microbial functions in reclaimed land.

13.
J Affect Disord ; 362: 529-535, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39013519

RESUMEN

BACKGROUND: Existing evidence suggests that anterior insula plays a crucial role in cognitive control and emotional regulation and is implicated in the onset and maintenance of bulimia nervosa (BN). However, it remains unclear how structural and functional abnormalities in specific subregions of anterior insula contribute to BN. METHODS: In this study, we analyzed structural MRI and resting-state functional MRI data from 54 BN patients and 56 healthy controls (HCs). We conducted voxel-based morphometry, amplitude of low frequency fluctuation (conventional band: 0.01-0.08 Hz, slow-5: 0.01-0.027 Hz) and seed-based whole-brain functional connectivity (FC) analysis of the anterior insula subregions for both groups. Additionally, we investigated the correlation between neuroimaging findings and clinical characteristics in the BN group. RESULTS: Our findings revealed that BN patients exhibited reduced gray matter volume in the right dorsal anterior insula (dAI) and bilateral ventral anterior insula (vAI) and demonstrated decreased ALFF in slow-5 band of bilateral dAI. The BN group also showed increased FC between bilateral dAI and precuneus or right superior frontal gyri which significantly correlated with the severity of BN or its key symptom. In addition, the decreased FC between bilateral vAI and anterior cingulate and paracingulate gyri and/or median cingulate and paracingulate gyri were both significantly correlated with the severity and its restrained eating behavior. CONCLUSIONS: Our findings further indicate that the functional separation of anterior insula subregions may underlie the pathophysiology of BN. Notably, the vAI associated with emotional processing may serve as a promising neuroimaging biomarker which could inform therapeutic strategy.


Asunto(s)
Bulimia Nerviosa , Cognición , Corteza Insular , Imagen por Resonancia Magnética , Humanos , Femenino , Bulimia Nerviosa/fisiopatología , Bulimia Nerviosa/diagnóstico por imagen , Adulto , Corteza Insular/fisiopatología , Corteza Insular/diagnóstico por imagen , Corteza Insular/fisiología , Adulto Joven , Cognición/fisiología , Emociones/fisiología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiopatología , Sustancia Gris/patología , Corteza Cerebral/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Estudios de Casos y Controles
14.
ACS Macro Lett ; 13(8): 903-907, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38990053

RESUMEN

High internal phase emulsion-templated polymer, named polyHIPE, has received widespread attention due to its great potential applications in many fields, such as separation, adsorption, heterogeneous catalysis, and sound absorption. The broad applicability is largely dependent on its adjustable opening structure. However, the question of why polyHIPE has an interconnected pore network structure is still to be discussed. Herein, different types (w/o, o/w, and o/o) of HIPEs are prepared and subsequently detected with laser scanning confocal microscopy (LSCM), and the polyHIPEs obtained by curing the HIPEs are characterized by SEM. The observations suggest that the interconnected pore formation is primarily due to the presence of the surfactant-rich phase in the film between the neighboring droplets in HIPE. The interconnected pores are generated by removal of the surfactant-rich domains in the postcuring procedure, and their sizes would be enlarged if the solubility of the surfactant in the continuous phase decreases in the curing stage.

15.
BMC Oral Health ; 24(1): 742, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937712

RESUMEN

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, characterized by high morbidity, high mortality, and poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) has been shown to be highly expressed in various cancers. However, its biological functions, potential role as a biomarker, and its relationship with immune infiltrates in HNSCC remain unclear. Our principal objective was to analyze CTHRC1 expression, its prognostic implications, biological functions, and its effects on the immune system in HNSCC patients using bioinformatics analysis. METHODS: The expression matrix was obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). CTHRC1 expression in HNSCC was analyzed between tumor and adjacent normal tissues, different stages were compared, and its impact on clinical prognosis was assessed using Kaplan-Meier analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA) were employed for enrichment analysis. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to analyze protein-protein interactions. Pearson correlation tests were used to investigate the association between CTHRC1 expression and immune checkpoints. The correlation between CTHRC1 and immune infiltration was investigated using CIBERSORT, TIMER, and ESTIMATE. RESULTS: Compared to adjacent normal tissues, CTHRC1 was found to be highly overexpressed in tumors. Increased expression of CTHRC1 was more evident in the advanced stage of HNSCC and predicted a poor prognosis. Most genes related to CTHRC1 in HNSCC were enriched in physiological functions of Extracellular matrix(ECM) and tumor. Furthermore, several immune checkpoints, such as TNFSF4 and CD276 have been shown to be associated with CTHRC1 expression. Notably, the level of CTHRC1 expression correlated significantly with immune infiltration levels, particularly activated macrophages in HNSCC. CONCLUSIONS: High expression of CTHRC1 predicts poor prognosis and is associated with immune infiltration in HNSCC, confirming its utility as a tumor marker for HNSCC. TRIAL REGISTRATION: Not applicable. All data are from public databases and do not contain any clinical trials.


Asunto(s)
Biomarcadores de Tumor , Proteínas de la Matriz Extracelular , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Biomarcadores de Tumor/metabolismo , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Biología Computacional , Masculino
16.
Gels ; 10(6)2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38920938

RESUMEN

Fly ash was used as raw material to prepare zeolites through silicate gels, assisted by the hydrothermal method. The silicate gels could be effectively formed in a few minutes in a molten alkali environment. The zeolites could be prepared by using these silicate gels through the hydrothermal method, which realizes the transformation from useless materials to highly valuable materials. The obtained zeolites were applied to the removal of ammonium in water, achieving the highvalue utilization of fly ash. The synthesized zeolites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrum (EDS), thermogravimetric (TG), and Fourier transform infrared (FTIR) spectroscopy. The study on the adsorption and removal of ammonium in water shows that the adsorption of ammonium is more in line with pseudo first-order kinetics, and the adsorption mainly occurs in the first 20 min. The adsorption can reach equilibrium in 30 min, and the maximum adsorption capacity can reach 49.1 mg/g. The adsorption capacity of ammonium has the best performance at pH = 5. Furthermore, within a certain range, an increase in temperature is beneficial for the removal of ammonium.

17.
PLoS One ; 19(6): e0291568, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38848420

RESUMEN

Polymeric IgMs are secreted from plasma cells abundantly despite their structural complexity and intricate multimerization steps. To gain insights into IgM's assembly mechanics that underwrite such high-level secretion, we characterized the biosynthetic process of a natural human IgM, SAM-6, using a heterologous HEK293(6E) cell platform that allowed the production of IgMs both in hexameric and pentameric forms in a controlled fashion. By creating a series of mutant subunits that differentially disrupt secretion, folding, and specific inter-chain disulfide bond formation, we assessed their effects on various aspects of IgM biosynthesis in 57 different subunit chain combinations, both in hexameric and pentameric formats. The mutations caused a spectrum of changes in steady-state subcellular subunit distribution, ER-associated inclusion body formation, intracellular subunit detergent solubility, covalent assembly, secreted IgM product quality, and secretion output. Some mutations produced differential effects on product quality depending on whether the mutation was introduced to hexameric IgM or pentameric IgM. Through this systematic combinatorial approach, we consolidate diverse overlapping knowledge on IgM biosynthesis for both hexamers and pentamers, while unexpectedly revealing that the loss of certain inter-chain disulfide bonds, including the one between µHC and λLC, is tolerated in polymeric IgM assembly and secretion. The findings highlight the differential roles of underlying non-covalent protein-protein interactions in hexamers and pentamers when orchestrating the initial subunit interactions and maintaining the polymeric IgM product integrity during ER quality control steps, secretory pathway trafficking, and secretion.


Asunto(s)
Inmunoglobulina M , Mutación , Humanos , Inmunoglobulina M/metabolismo , Inmunoglobulina M/genética , Células HEK293 , Multimerización de Proteína , Subunidades de Proteína/metabolismo , Subunidades de Proteína/genética , Retículo Endoplásmico/metabolismo
18.
Molecules ; 29(12)2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38930926

RESUMEN

The effective treatment and recovery of fracturing wastewater has always been one of the difficult problems to be solved in oilfield wastewater treatment. Accordingly, in this paper, photocatalytic-coupled low-temperature plasma technology was used to degrade the simulated wastewater containing hydroxypropyl guar, the main component of fracturing fluid. Results indicated that hydroxypropyl-guar wastewater could be degraded to a certain extent by either photocatalytic technology or plasma technology; the chemical oxygen demand and viscosity of the treated wastewater under two single-technique optimal conditions were 781 mg·L-1, 0.79 mPa·s-1 and 1296 mg·L-1, 1.01 mPa·s-1, respectively. Furthermore, the effective coupling of AgIn5S8/gC3N4 photocatalysis and dielectric-barrier discharge-low-temperature plasma not only enhanced the degradation degree of hydroxypropyl guar but also improved its degradation efficiency. Under the optimal conditions of coupling treatment, the hydroxypropyl-guar wastewater achieved the effect of a single treatment within 6 min, and the chemical oxygen demand and viscosity of the treated wastewater reduced to below 490 mg·L-1 and 0.65 mPa·s-1, respectively. In the process of coupled treatment, the AgIn5S8/gC3N4 could directly absorb the light and strong electric field generated by the system discharge and play an important role in the photocatalytic degradation, thus effectively improving the energy utilization rate of the discharge system and enhancing the degradation efficiency of hydroxypropyl guar.

19.
Transl Oncol ; 46: 102002, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38797017

RESUMEN

Lung cancer is a highly prevalent malignancy with poor prognosis and rapid progression. It most frequently metastasizes to the bone, where it can pose a severe threat to the patient's survival. Once metastasized, the disease is often incurable and can result in severe complications such as hypercalcemia, bone pain, fractures, spinal cord compression, and subsequent paralysis. Exosomes are bilayer vesicle nanoparticles secreted by most of the extracellular vesicles, which can be found in almost all organisms and play an essential role in intercellular communication. Through their ability to regulate related bone cells, exosomes carry bioactive molecules, including proteins, lipids, and non-coding RNAs (ncRNAs), that can be extremely important in bone remodeling. Studies have been conducted on the role play by proteins, lncRNA, and microRNA-all ncRNAs-carried by exosomes in the bone metastases of lung cancer. In this review, the latest progress of the regulatory mechanism of ncRNAs carried by exosomes in lung cancer bone metastasis has been reviewed. The clinical use of exosomes as a promising biomarker, drug transporter, and therapeutic target was highlighted to offer a novel diagnostic and treatment approach for patients with lung cancer bone metastases.

20.
Plants (Basel) ; 13(10)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38794406

RESUMEN

Disentangling how climate oscillations and geographical events significantly influence plants' genetic architecture and demographic history is a central topic in phytogeography. The deciduous ancient tree species Ulmus macrocarpa is primarily distributed throughout Northern China and has timber and horticultural value. In the current study, we studied the phylogenic architecture and demographical history of U. macrocarpa using chloroplast DNA with ecological niche modeling. The results indicated that the populations' genetic differentiation coefficient (NST) value was significantly greater than the haplotype frequency (GST) (p < 0.05), suggesting that U. macrocarpa had a clear phylogeographical structure. Phylogenetic inference showed that the putative chloroplast haplotypes could be divided into three groups, in which the group Ⅰ was considered to be ancestral. Despite significant genetic differentiation among these groups, gene flow was detected. The common ancestor of all haplotypes was inferred to originate in the middle-late Miocene, followed by the haplotype overwhelming diversification that occurred in the Quaternary. Combined with demography pattern and ecological niche modeling, we speculated that the surrounding areas of Shanxi and Inner Mongolia were potential refugia for U. macrocarpa during the glacial period in Northern China. Our results illuminated the demography pattern of U. macrocarpa and provided clues and references for further population genetics investigations of precious tree species distributed in Northern China.

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