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1.
Genet Test Mol Biomarkers ; 28(4): 144-150, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38657122

RESUMEN

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) (EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.


Asunto(s)
Pueblo Asiatico , Proteína 3 de la Respuesta de Crecimiento Precoz , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Esquizofrenia , Humanos , Esquizofrenia/genética , Polimorfismo de Nucleótido Simple/genética , Proteína 3 de la Respuesta de Crecimiento Precoz/genética , Femenino , Masculino , Predisposición Genética a la Enfermedad/genética , Estudios de Casos y Controles , Adulto , China/epidemiología , Pueblo Asiatico/genética , Persona de Mediana Edad , Genotipo , Factores de Riesgo , Frecuencia de los Genes/genética , Alelos , Receptor ErbB-4/genética , Pueblos del Este de Asia
2.
Mol Biol Rep ; 51(1): 520, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38625436

RESUMEN

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.


Asunto(s)
Azitromicina , Síndrome de QT Prolongado , Humanos , Azitromicina/efectos adversos , Células HEK293 , Antibacterianos/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/genética , Mutación
3.
Arch Toxicol ; 98(5): 1543-1560, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38424264

RESUMEN

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.


Asunto(s)
Cisplatino , Neoplasias de la Vejiga Urinaria , Humanos , Especies Reactivas de Oxígeno/metabolismo , Cisplatino/farmacología , Línea Celular Tumoral , Proliferación Celular , Apoptosis , Antioxidantes/farmacología , Daño del ADN , Caspasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética
4.
Front Microbiol ; 15: 1320095, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38298894

RESUMEN

Background: The associations between gut microbiota and cardiovascular disease have been reported in previous studies. However, the relationship between gut microbiota and endocarditis remains unclear. Methods: A bidirectional Mendelian randomization (MR) study was performed to detect the association between gut microbiota and endocarditis. Inverse variance weighted (IVW) method was considered the main result. Simultaneously, heterogeneity and pleiotropy tests were conducted. Results: Our study suggests that family Victivallaceae (p = 0.020), genus Eubacterium fissicatena group (p = 0.047), genus Escherichia Shigella (p = 0.024), genus Peptococcus (p = 0.028) and genus Sellimonas (p = 0.005) play protective roles in endocarditis. Two microbial taxa, including genus Blautia (p = 0.006) and genus Ruminococcus2 (p = 0.024) increase the risk of endocarditis. At the same time, endocarditis has a negative effect on genus Eubacterium fissicatena group (p = 0.048). Besides, no heterogeneity or pleiotropy was found in this study. Conclusion: Our study emphasized the certain role of specific gut microbiota in patients with endocarditis and clarified the negative effect of endocarditis on gut microbiota.

5.
Zootaxa ; 5399(1): 65-78, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38221175

RESUMEN

The genera Echinovelleda Breuning, 1936 and Propedicellus Huang, Huang & Liu, 2020 are revised. The latterisconsideredto be ajunior synonym of theformer based on a comprehensive morphological investigation, especially on the characteristics of male endophallus. Two new species are described from China, viz. Echinovelleda mumuae Bi & Mu sp. nov. from Yunnan and Guangxi, and E. protochinensis Bi & Lin sp. nov. from Yunnan and Sichuan. New records are reported for previously described taxa including one new country record of a morphologically similar genus, Hechinoschema Thomson, 1857 from China. Illustrations of habitus, endophallic structure, major diagnostic features for all studied taxa, as well as a distributional map are provided.


Asunto(s)
Escarabajos , Masculino , Animales , Estructuras Animales , Tamaño Corporal , China , Tamaño de los Órganos
6.
Front Endocrinol (Lausanne) ; 14: 1271395, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38027198

RESUMEN

Introduction: This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty. Methods: A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children's Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment. Results: The treatment group was significantly older at the time of inclusion(chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht)(PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH-PAH1≥5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year. Discussion: GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain.


Asunto(s)
Hormona Liberadora de Gonadotropina , Pubertad Precoz , Niño , Femenino , Humanos , Adulto , Hormona Liberadora de Gonadotropina/farmacología , Pubertad Precoz/tratamiento farmacológico , Estudios Retrospectivos , Estatura , Pubertad
7.
J Neuroinflammation ; 20(1): 247, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880726

RESUMEN

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Factores de Transcripción NFI , Canales Catiónicos TRPV , Animales , Humanos , Ratones , 4-Aminopiridina/efectos adversos , Astrocitos/metabolismo , Encéfalo/metabolismo , Sistema Nervioso Central/metabolismo , Epilepsia/metabolismo , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/metabolismo , Factores de Transcripción NFI/genética , Factores de Transcripción NFI/metabolismo , Canales Catiónicos TRPV/metabolismo , Regulación hacia Arriba
8.
RSC Adv ; 13(44): 30771-30776, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37869386

RESUMEN

In this work, a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe, 2-(2'-hydroxy-4'-aminophenyl)benzimidazole (4-AHBI), was synthesized and its fluorescent behavior toward triphosgene were evaluated. The results showed that 4-AHBI exhibited high sensitivity (limit of detection, 0.08 nM) and excellent selectivity for triphosgene over other acyl chlorides including phosgene in CH2Cl2 solution. Moreover, 4-AHBI loaded test strips were prepared for the practical sensing of triphosgene.

9.
Se Pu ; 41(10): 901-910, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-37875412

RESUMEN

This paper reviews the application of deep eutectic solvents (DESs) in the synthesis of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as well as their prospects in the field of solid-phase extraction (SPE). Porous organic frameworks (POFs) have unique properties such as a large specific surface area, high porosity, and easy modification. Thus, these materials are widely applied in the fields of catalysis, adsorption, drug delivery, gas storage, and separation. POFs include MOFs, COFs, conjugated microporous polymers (CMPs), porous aromatic frameworks (PAFs), and covalent triazine frameworks (CTFs). MOFs are constructed from metal ions/clusters and organic ligands through coordination bonds and can be extended in two or three dimensions by repeated coordination with potential voids. COFs are formed from two monomers containing light elements (such as carbon, hydrogen, oxygen, nitrogen, boron, and other elements) via coordination bonds and have large two- or three-dimensional structures. However, conventional POF synthesis methods generally suffer from disadvantages such as long synthesis times, high temperature and pressure requirements, and the use of toxic and hazardous reaction solvents. DES consists of a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) bound by hydrogen-bonding interactions. It is a promising green solvent for material synthesis owing to its low vapor pressure, high stability, and ease of preparation. DES can be used to prepare MOFs and COFs and, in specific cases, acts as a structure-directing agent, which has an important impact on the structure and properties of the resulting frameworks. Using appropriate DES formulations, researchers can modulate the crystal structures, pore sizes, and surface properties of MOFs and COFs, resulting in materials with excellent characteristics. SPE is an analytical technique in which a sample solution is added to an SPE column; the sample solution is forced through the stationary phase, and the target compounds are collected for analysis by elution with an organic solvent. Therefore, suitable stationary-phase materials are critical for SPE. Owing to their large specific surface areas and abundant active sites, MOFs and COFs exhibit outstanding adsorption capacity and selectivity in SPE and can effectively enrich target analytes from complex samples. DES-based MOFs and COFs have shown potential use in a wide range of applications, such as in environmental analysis, food testing, and biological sample analysis. Although DES-based MOFs and COFs for SPE are still in the early stages of development, their properties such as efficient enrichment and high selectivity offer good prospects for practical applications. Future research should continue to explore DES-based synthesis methods in depth to prepare other MOFs and COFs with the desired properties and investigate their potential applications in various fields. These efforts are expected to apply these novel materials in commercialized solid-phase extraction methods, bringing new development opportunities in the field of analytical chemistry.

10.
Bioorg Chem ; 141: 106909, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37832221

RESUMEN

ß-Glucuronidase (GUSB) plays an important role in human physiological and pathological activities. The activity level of GUSB is closely related to human health and diseases. It is imperative to detect the activity of GUSB for related disease diagnosis and treatment. However, exactly evaluating the activity of GUSB in complicated biological system remains a challenge. In this study, we developed photoaffinity-based probes (AfBPs) equipped with photosensitive benzophenone group for labeling active GUSB. Through molecule docking, we predicted the binding model of the AfBPs and GUSB, and the obtained results suggested thermodynamically favorable binding. The AfBPs indicated high efficiency and showed dose-/time-dependent labeling of Escherichia coli (E. coli) GUSB. The application of AfBPs toward GUSB provides a powerful tool to study the activity of target enzymes and contributes to huge potential of enzyme inhibitor discovery and biomedical diagnostics.


Asunto(s)
Escherichia coli , Glucuronidasa , Humanos , Glucuronidasa/metabolismo , Escherichia coli/metabolismo
11.
Cancer Sci ; 114(12): 4535-4547, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37750019

RESUMEN

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.


Asunto(s)
MicroARNs , Neoplasias de la Tiroides , Humanos , Línea Celular Tumoral , Neoplasias de la Tiroides/patología , Cáncer Papilar Tiroideo/patología , Carcinogénesis/genética , Transformación Celular Neoplásica/genética , Proliferación Celular/genética , Tetraspaninas/genética , Tetraspaninas/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética
12.
J Orthop Surg Res ; 18(1): 676, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37700350

RESUMEN

BACKGROUND: Observational studies can suggest potential associations between variables but cannot establish a causal effect on their own. This study explored the causal associations between body mass index (BMI), physical activity (PA), and joint sports injuries. METHODS: We conducted two-sample Mendelian randomization (MR) using publicly accessed genome-wide association studies (GWAS) datasets to investigate the causal effects of BMI and PA on joint sports injury risk. The inverse-variance weighted method was believed to be the primary MR analysis. Subsequently, sensitivity, pleiotropy, and heterogeneity analyses were employed to estimate the reliability of the results of the current research. RESULTS: Genetically predicted increased BMI was causally related to the higher sports injury risk of the ankle-foot (OR 1.23, 95% CI 1.09-1.37, p = 4.20E-04), knee (OR 1.32, 95% CI 1.21-1.43, p = 1.57E-11), and shoulder (OR 1.23, 95% CI 1.08-1.40, p = 1.28E-03). Further, the mentioned effects were validated using another set of GWAS data on BMI. Similar causal linkages were exhibited between increased BMI and the growing risk of sports injuries of the ankle-foot (OR 1.34, 95% CI 1.13-1.60, p = 9.51E-04), knee (OR 1.26, 95% CI 1.09-1.45, p = 1.63E-03), and shoulder (OR 1.35, 95% CI 1.09-1.67, p = 5.66E-03). Additionally, accelerometer-based PA measurement (overall average acceleration) (AccAve) was negatively related to sports injuries of the ankle-foot (OR 0.93, 95% CI 0.87-0.99, p = 0.046) and lumbar spine (OR 0.68, 95% CI 0.51-0.92, p = 0.012). Furthermore, we verified that the effect of AccAve on the risk of injury at the ankle-foot still had statistical significance after adjusting BMI. Results were verified as reliable under all sensitive analyses. CONCLUSIONS: This research determined that a higher BMI could raise the sports injury risk of the ankle-foot, knee, and shoulder, while an overall average acceleration PA could reduce the injury risk of the ankle-foot and lumbar spine. These conclusions contribute to a greater knowledge of the roles of BMI and PA in the mechanism of joint sports injuries and offer several suggestions for patients and clinicians.


Asunto(s)
Traumatismos en Atletas , Humanos , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/genética , Índice de Masa Corporal , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Reproducibilidad de los Resultados , Ejercicio Físico
13.
Rev. int. med. cienc. act. fis. deporte ; 23(92): 180-190, aug.-sept. 2023. tab, graf
Artículo en Inglés | IBECS | ID: ibc-229397

RESUMEN

Objective: This study aims to evaluate the efficacy of secondary sentinel lymph node (SLN) biopsy in cN1a papillary thyroid carcinoma (PTC) surgery, drawing parallels to strategic approaches akin to those employed by athletic players.Methods: We selected eleven patients diagnosed with suspected cN1a PTC from January 2020 to July 2020. Carbon nanoparticles were utilized to mark lymph nodes, analogous to strategic marking in athletic games, ensuring precise identification during surgery. The secondary SLN biopsy technique was implemented, reflecting the precision and planning seen in athletic strategies.Results: The average tumor size was 12.64±5.63 mm. Notably, 2 patients exhibited extrathyroidal spread, 3 had thyroiditis, and all had neck metastases. The SLN identification rate stood at 100%, mirroring the accuracy expected in athletic performance. Out of the group, 3 patients had sentinel lymph node metastasis, with additional metastasis in non-SLN areas in 1 patient. The detection rate, false-negative rate, and overall accuracy paralleled the high performance and reliability seen in athletic endeavors. A total of 42 lateral SLNs were identified, with the majority being grade IV. This strategic identification is akin to an athlete's ability to focus on key areas during play (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Biopsia del Ganglio Linfático Centinela , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Carcinoma/diagnóstico , Carcinoma/patología , Atletas
14.
Diabetes Metab Syndr Obes ; 16: 2225-2232, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37525823

RESUMEN

Background: Thyroxine binding globulin (TBG) deficiency is a rare thyroid disease, mostly caused by genetic mutations and acquired by X-linked recessive inheritance. The clinical features of children with TBG deficiency and their family members were summarised and the Serpina7 gene mutation was analysed, providing a reference for the differentiation of TBG deficiency. Methods: Thyroid function was detected in TBG deficient patients, and genetic analysis was performed using polymerase chain reaction (PCR) and direct DNA sequencing to detect the characteristics of TBG mutants. Using "thyroxine binding globulin, gene and mutation" as keywords, PubMed (biomedical literature database), Web of Science and other databases were searched for relevant studies to collect and summarise relevant information. Results: The TBG (14.7 µg/mL), 70% triiodothyronine (T3) (<0.3 nmol/L), total T3 (Tr3) (<0.05 ng/mL) and thyroxine (T4) (14.72 nmol/L) values were lower than normal, while the thyrotropin (TSH) (2.33 uIU/mL), free T3 (FT3) (1.62 pmol/L), and free T4 (FT4) (11.39 pmol/L) values were normal. These values indicate a TBG partially deficient phenotype. Using PCR amplification and direct sequencing of the target gene, a missense mutation in exon 4 of the Serpina7 gene was found in the patient and the father, and the nucleic acid variant was C.909 (exon 4) g > T; the patient was heterozygous and the father was hemizygous. The literature search retrieved a total of 45 studies, most of which were related to mutations in the Serpina7 gene. The mutation locations included exons, introns, enhancers and promoters, with exons the predominant location. A total of 49 variants of the Serpina7 gene were identified. Conclusion: Serpina7 C.909G (P.L303F) is a mutation acquired from the father by X-linked recessive inheritance. The main clinical features of TBG deficiency patients are low serum T4, T3 and TBG levels, normal TSH, FT3 and FT4 levels, and no clinical manifestations.

15.
Front Physiol ; 14: 1123182, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37650112

RESUMEN

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relative toxin removal methods, and elucidate promising approaches to effectively remove toxins.

16.
Aging (Albany NY) ; 15(14): 7161-7186, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37494663

RESUMEN

Immunotherapy has become a revolutionary treatment for cancer and brought new vitality to tumor immunity. Bone metastases are the most prevalent metastatic site for advanced prostate cancer (PCa). Therefore, finding new immunotherapy targets in PCa patients with bone metastasis is urgently needed. We conducted an elaborative bioinformatics study of immune-related genes (IRGs) and tumor-infiltrating immune cells (TIICs) in PCa bone metastases. Databases were integrated to obtain RNA-sequencing data and clinical prognostic information. Univariate and multivariate Cox regression analyses were conducted to construct an overall survival (OS) prediction model. GSE32269 was analyzed to acquire differentially expressed IRGs. The OS prediction model was established by employing six IRGs (MAVS, HSP90AA1, FCGR3A, CTSB, FCER1G, and CD4). The CIBERSORT algorithm was adopted to assess the proportion of TIICs in each group. Furthermore, Transwell, MTT, and wound healing assays were employed to determine the effect of MAVS on PCa cells. High-risk patients had worse OS compared to the low-risk patients in the training and validation cohorts. Meanwhile, clinically practical nomograms were generated using these identified IRGs to predict the 3- and 5-year survival rates of patients. The infiltration percentages of some TIICs were closely linked to the risk score of the OS prediction model. Some tumor-infiltrating immune cells were related to the OS. FCGR3A was closely correlated with some TIICs. In vitro experiments verified that up-regulation of MAVS suppressed the proliferation and metastatic abilities of PCa cells. Our work presented a thorough interpretation of TIICs and IRGs for illustrating and discovering new potential immune checkpoints in bone metastases of PCa.


Asunto(s)
Neoplasias Óseas , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/genética , Neoplasias Óseas/genética , Algoritmos , Bioensayo , Biología Computacional , Pronóstico
17.
Mol Neurobiol ; 60(9): 5482-5492, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37316759

RESUMEN

Mitochondria are the structures in cells that are responsible for producing energy. They contain a specific translation unit for synthesizing mitochondria-encoded respiratory chain components: the mitochondrial DNA (mt DNA). Recently, a growing number of syndromes associated with the dysfunction of mt DNA translation have been reported. However, the functions of these diseases still need to be precise and thus attract much attention. Mitochondrial tRNAs (mt tRNAs) are encoded by mt DNA; they are the primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. Previous research has shown the role of mt tRNAs in the epileptic mechanism. This review will focus on the function of mt tRNA and the role of mitochondrial aminoacyl-tRNA synthetase (mt aaRS) in order to summarize some common relevant mutant genes of mt aaRS that cause epilepsy and the specific symptoms of the disease they cause.


Asunto(s)
Aminoacil-ARNt Sintetasas , Epilepsia , Humanos , Aminoacil-ARNt Sintetasas/genética , Aminoacil-ARNt Sintetasas/metabolismo , Mutación/genética , Mitocondrias/metabolismo , Biosíntesis de Proteínas , Epilepsia/patología , ARN de Transferencia/genética , ARN de Transferencia/metabolismo
18.
BMC Cancer ; 23(1): 509, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37277745

RESUMEN

OBJECTIVE: E2F1 has been confirmed to be highly expressed in a variety of cancers. To better understand the prognostic value of E2F1 in cancer patients, this study was conducted to comprehensively evaluate the prognostic value of E2F1 in cancer according to published data. METHOD: PubMed, Web of Science and CNKI database were searched until May 31th, 2022 by using key words to retrieve the published essays on the role of E2F1 expression in the prognostic value of cancer. The essays were identified according to the inclusion and exclusion criteria. The pooled result of hazard ratio and 95% confidence interval was calculated with Stata17.0 software. RESULT: A total of 17 articles were included in this study involved in 4481 cancer patients. The pooled results showed that higher E2F1 expression was significantly correlated with unfavorable overall survival (HR = 1.10, I2 = 95.3%, *PHeterogeneity = 0.000) and disease-free survival (HR = 1.41, I2 = 95.2%, *PHeterogeneity = 0.000) of cancer patients. Such a significant association of was maintained subgroup of sample size of patients (> 150: for OS, HR = 1.77, and for DFS, HR = 0.91; or < 150: for OS, HR = 1.93, and for DFS, HR = 4.39), ethnicity (Asian: for OS, HR = 1.65, and for DFS, HR = 1.08; or not Asian: HR = 3.55, and for DFS, HR = 2.87), the data from database (clinical: for OS, HR = 1.24, and for DFS, HR = 1.40; or database: for OS, HR = 2.29, and for DFS, HR = 3.09), paper published year (after 2014: for OS, HR = 1.90;and for DFS,HR = 1.87; or before 2014: for OS, HR = 1.40, and for DFS, HR = 1.22); cancer type (female specific cancer: for OS, HR = 1.41, and for DFS, HR = 0.64; or non-gender specific cancers: for OS, HR = 2.00, and for DFS, HR = 2.95). In addition, according to the database data, we also found that higher E2F1 expression level would lead to worse prognosis of patients, and the results were consistent with the statistical analysis results in the paper. CONCLUSION: E2F1 could be served as a prognostic biomarker in cancer patients and higher levels of in cancer patients could predict shorter overall survival and disease-free survival.


Asunto(s)
Neoplasias , Humanos , Femenino , Pronóstico , Neoplasias/genética , Neoplasias/metabolismo , Supervivencia sin Enfermedad , Supervivencia sin Progresión , Expresión Génica , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo
19.
Food Funct ; 14(14): 6482-6495, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37366083

RESUMEN

As a dietary supplement, hyaluronic acid (HA) has exhibited appreciable immunomodulatory activity and an ameliorative effect on rodent colitis. However, its high viscosity is not only refractory to absorb through the gut, but also causes flatulence. In contrast to HA, hyaluronic acid oligosaccharides (o-HAs) can overcome the above-mentioned constraints, but their treatment effect still remains ill-defined contemporarily. Herein, the current study intends to compare the modulatory effects of HA and o-HA on colitis and assess the underlying molecular mechanism. We first showed that o-HA had a better preventive effect than HA in alleviating colitis symptoms, as evidenced by lower body weight loss, lower disease activity index scores, a lower inflammatory response (TNF-α, IL-6, IL-1ß, p-NF-κB), and more intact colon epithelial integrity in vivo. The best efficiency was observed in the o-HA treated group with a dosage of 30 mg kg-1. In an in vitro barrier function assay, o-HA exerted a better protective effect on the transepithelial electrical resistance (TEER), FITC permeability, and wound healing and modulated the expression of tight junction (TJ) proteins (ZO-1, occludin) in lipopolysaccharide (LPS)-stimulated Caco-2 cells. In summary, both HA and o-HA showed the potential to reduce inflammation and ameliorate intestinal damage in DSS-induced colitis and LPS-induced inflammation, but o-HA had improved outcomes. The results also provided a glimpse of the latent mechanism by which HA and o-HA enhanced intestinal barrier function via MLCK/p-MLC signaling pathway suppression.


Asunto(s)
Colitis , Ácido Hialurónico , Humanos , Ratones , Animales , Ácido Hialurónico/farmacología , Células CACO-2 , Mucosa Intestinal/metabolismo , Lipopolisacáridos/efectos adversos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Inflamación/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Sulfato de Dextran/efectos adversos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
20.
Pathol Res Pract ; 247: 154544, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37235911

RESUMEN

MicroRNA-27a (miR-27a) has been reported to be abnormally expressed in patients with cancer, and it could play potential roles as a diagnostic and prognostic biomarker of cancers. However, the diagnostic and prognostic role remains unclear. Hence, this meta-analysis, based on published data, was conducted to assess the utility of miR-27a as a diagnostic and prognostic marker in various cancers. To identify eligible studies, databases: Web of Science, PubMed, and CNKI were searched, with 868 literatures obtained, 16 of which were included in the Meta-analysis. The pooled results of studies conducted with serum/plasma showed that miR-27a was a valuable diagnostic biomarker in cancers (area under curve (AUC)= 0.91, sensitivity (SEN)= 0.84, specificity (SPE)= 0.85), with the diagnostic value slightly reduced in tumor tissue samples (AUC=0.83, SEN=0.78, SPE: 0.74). Additionally, the pooled results revealed that high expression of miR-27a predicted poor prognosis of cancer in serum/plasma (hazard ratio (HR) = 0.63, PHeterogeneity = 0.278, I2= 21.50%) but not in tumor tissue (HR = 0.98, PHeterogeneity =0.577, I2= 0.0). In brief, our results suggested that miR-27a in serum/plasma or tumor tissue could act as a diagnostic biomarker, and that miR-27a in serum/plasma could predict cancer patients' survival.


Asunto(s)
MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias/diagnóstico , Neoplasias/genética , Modelos de Riesgos Proporcionales
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