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1.
J Cell Mol Med ; 28(8): e18247, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38520212

RESUMEN

Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.


Asunto(s)
Melanoma , MicroARNs , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , MicroARNs/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Línea Celular Tumoral , Neoplasias Cutáneas/genética , Sistemas de Liberación de Medicamentos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismo
2.
Liver Int ; 44(2): 330-343, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38014574

RESUMEN

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.


Asunto(s)
Inteligencia Artificial , Enfermedad del Hígado Graso no Alcohólico , Humanos , Algoritmos , Tecnología , Hepatocitos
3.
Liver Int ; 43(6): 1170-1182, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37017559

RESUMEN

Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in 'real life' situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Hígado/patología , Inteligencia Artificial , Proteínas Hedgehog , Índice de Severidad de la Enfermedad , Biopsia
4.
BMC Plant Biol ; 22(1): 512, 2022 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-36324083

RESUMEN

BACKGROUND: Calcineurin B-like proteins (CBLs) are ubiquitous Ca2+ sensors that mediate plant responses to various stress and developmental processes by interacting with CBL-interacting protein kinases (CIPKs). CBLs and CIPKs play essential roles in acclimatization of crop plants. However, evolution of these two gene families in the genus Medicago is poorly understood. RESULTS: A total of 68 CBL and 135 CIPK genes have been identified in five genomes from Medicago. Among these genomes, the gene number of CBLs and CIPKs shows no significant difference at the haploid genome level. Phylogenetic and comprehensive characteristic analyses reveal that CBLs and CIPKs are classified into four clades respectively, which is validated by distribution of conserved motifs. The synteny analysis indicates that the whole genome duplication events (WGDs) have contributed to the expansion of both families. Expression analysis demonstrates that two MsCBLs and three MsCIPKs are specifically expressed in roots, mature leaves, developing flowers and nitrogen fixing nodules of Medicago sativa spp. sativa, the widely grown tetraploid species. In particular, the expression of these five genes was highly up-regulated in roots when exposed to salt and drought stress, indicating crucial roles in stress responses. CONCLUSIONS: Our study leads to a comprehensive understanding of evolution of CBL and CIPK gene families in Medicago, but also provides a rich resource to further address the functions of CBL-CIPK complexes in cultivated species and their closely related wild relatives.


Asunto(s)
Sequías , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Medicago/metabolismo , Filogenia , Proteínas Serina-Treonina Quinasas/genética , Cloruro de Sodio/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Unión al Calcio/genética
5.
Horm Metab Res ; 54(1): 50-51, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34327681

RESUMEN

Luo et al. 1 reported two cases of autosomal dominant pseudohypoparathyroidism type 1B (AD-PHP1B) and reviewed literature about the genetic and epigenetic characteristics of AD-PHP1B. Pseudohypoparathyroidism (PHP) is a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH). PHP1B almost results from methylation abnormalities of the maternal differentially methylated regions (DMRs) and can be divided into sporadic PHP1B and AD-PHP1B 1. As mentioned in this article 1, AD-PHP1B is caused by heterozygous maternal deletions within GNAS or STX16, which are associated with loss of methylation at the A/B DMR alone or at all maternally methylated GNAS exons. While sporadic PHP1B remains unclear at the molecular level, except for approximately 10% of the patients caused by paternal uniparental isodisomy or heterodisomy involving chromosome 20q (patUPD20q) 2. Here, we would like to present a rare case of sporadic PHP1B occurring in association with hypokalemia.


Asunto(s)
Hipopotasemia/complicaciones , Seudohipoparatiroidismo/complicaciones , Adolescente , Femenino , Humanos , Seudohipoparatiroidismo
6.
Horm Metab Res ; 52(11): 788-795, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32299109

RESUMEN

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited endocrine tumor syndrome caused by inactivating variants of the MEN1 gene. The aim of this study is to explore the clinical and genetic characteristics of four MEN1 patients. We isolated genomic deoxyribonucleic acid from lymphocytes, parathyroid, and thymic tumoral tissue specimens from the MEN1 patients. All exons of the MEN1 and CDNK1B genes and adjacent exon-intron sequences were amplified by polymerase chain reaction and subsequently sequenced. Further, the splice alterations were studied by sequencing the amplified RT-PCR products for MEN1 cDNA. We identified four heterozygous MEN1 germline variants: c.564delC, c.1268G>A, IVS5+5delG, and c.1546_1547insC. Both c.564delC and IVS5+5delG were novel variants. The impact of the MEN1 splice variant, IVS5+5delG, was evaluated using bioinformatics and in vitro analyses. The analyses indicated that this variant resulted in skipping of the neighboring exon and was disease-causing. Two novel somatic variants, c.249_252delGTCT and c.313_314insC, were found. Additionally, loss of heterozygosity (LOH) for the MEN1 locus (IVS5+5delG and c.564delC) was found in tumor tissue samples from the MEN1 patients, consistent with Knudson's two-hit mechanism. We identified four MEN1 germline variants and two novel somatic variants. Early recognition of the phenotype coupled with variant screening of the MEN1 gene is the key to diagnosing and treating MEN1 effectively at an early stage.


Asunto(s)
Neoplasia Endocrina Múltiple Tipo 1/patología , Mutación , Fenotipo , Proteínas Proto-Oncogénicas/genética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/genética
7.
Carcinogenesis ; 39(12): 1477-1487, 2018 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-30256916

RESUMEN

MicroRNA-34a (miR-34a) behaves as a tumor suppressor by decreasing the expression of oncogenes involved in multiple carcinogenic pathways. Intravenous delivery of miR-34a mimics has been investigated in clinical trials as a potential treatment for advanced cancers; however, the effect of miR-34a on cancer immune surveillance is controversial. In the current study, we found that miR-34a plays a dual role in the regulation of major histocompatibility complex class I-related sequence B (MICB) protein, a ligand of the NKG2D receptor. MiR-34a could both induce and reduce MICB expression by upregulating ataxia telangiectasia and Rad3-related (ATR) protein kinase and downregulating the transcription factor E2F1, respectively. The net effect of miR-34a on MICB expression depended on endogenous E2F1 levels. Overexpression of miR-34a promoted MICB expression in hepatocytes and hepatocellular carcinoma (HCC) cells that have low E2F1 levels but not in HCC cells that have high E2F1 levels. In HCC patients, the expression of miR-34a and MICB showed positive correlation in paratumor liver tissues, which have low E2F1 levels, but not in HCC tissues, which have high E2F1 levels. We showed that miR-34a overexpression in non-transformed liver cells enhanced cytolysis and interferon-γ production by NK-92MI cells. Furthermore, higher miR-34a expression in tumor and paratumor tissues was associated with positive and negative outcomes, respectively, in HCC patients. Our findings suggest that miR-34a induces MICB expression in paratumor liver tissues, which may cause liver damage and serious cytokine release syndrome, thus disclosing potential side effects of systemic administration of miR-34a in anticancer therapy.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Hepatocitos/patología , Antígenos de Histocompatibilidad Clase I/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Proteínas de la Ataxia Telangiectasia Mutada/genética , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Regulación hacia Abajo/genética , Factor de Transcripción E2F1/genética , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Interferón gamma/genética , Células Asesinas Naturales , Oncogenes/genética , Regulación hacia Arriba/genética
8.
World J Surg Oncol ; 15(1): 144, 2017 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-28764808

RESUMEN

BACKGROUND: Though a number of studies have been conducted to explore the association between myeloperoxidase (MPO)-463G > A polymorphism and cancer risk, the results remain inconsistent. Therefore, we performed a meta-analysis to derive a more systematic estimation of this relationship. METHOD: Relevant studies were searched by PubMed, EMBASE, CNKI, Google Scholar, Ovid, and Cochrane library prior to December 2015. The strength of the association between MPO-463G > A polymorphism and cancer risk was estimated by odds ratios (OR) with 95% confidence interval (95%CI). Cumulative analysis was used to evaluate the stability of results through time. RESULTS: The current analysis consisted of 16,858 cases and 21,756 controls from 60 studies. Pooled results showed that MPO-463G > A polymorphism were associated with the overall decreased cancer susceptibility in all the genetic models included in this study (additive model: OR = 0.84, 95%CI = 0.76-0.94; allele genetic model: OR = 0.90, 95%CI = 0.840-0.954; recessive genetic model: OR = 0.89, 95%CI = 0.83-0.95). However, in the stratified analysis of cancer type, the significant results were only found in lung cancer (dominant model: OR = 0.93, 95%CI = 0.87-0.99) and digestive system cancer groups (dominant model: OR = 0.67 0.53-0.84; allele frequency model = 0.71, 95%CI = 0.57-0.87), but not in the blood system cancer or breast cancer group. When we further stratified the digestive system cancer group into digestive tract and digestive gland cancer groups, results showed a significant association between allele A of MPO-463G > A and digestive gland cancer in all the genetic models (allele frequency model: OR = 0.63, 95%CI = 0.40-0.99; additive model: OR = 0.41, 95%CI = 0.23-0.73; recessive model: OR = 0.51, 95%CI = 0.29-0.89; dominant model: OR = 0.58, 95%CI = 0.35-0.96), digestive tract cancers in allele frequency model (OR = 0.75, 95%CI = 0.59-0.95), and dominant model (OR = 0.72, 95%CI = 0.56-0.92). When stratified by ethnicity, results demonstrated that the genotype A might be a protect factor for both Caucasians and Asians. In group analysis according to source of controls, significant results were found in population from hospital in all the genetic models. In cumulative analysis, result of allele contrast showed a declining trend and increasingly narrower 95% overall, while the inclination toward non-significant association with lung cancer risk. CONCLUSIONS: This meta-analysis suggested that MPO-463G > A polymorphism was associated with the overall reduced cancer susceptibility significantly. It might be a more reliable predictor of digestive system cancer instead of lung cancer, blood system cancer, and breast cancer. In cumulative analysis, the stable trend indicated that evidence was sufficient to show the association between MPO-463G > A polymorphism and cancer risk.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias/genética , Peroxidasa/genética , Adenina/metabolismo , Pueblo Asiatico/genética , Frecuencia de los Genes , Genotipo , Guanina/metabolismo , Humanos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple/genética , Pronóstico , Factores de Riesgo , Población Blanca/genética
9.
J Cell Mol Med ; 20(5): 903-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26820236

RESUMEN

Xeroderma pigmentosum group G (XPG) protein plays an important role in the DNA repair process by cutting the damaged DNA at the 3' terminus. Previous studies have indicated some polymorphisms in the XPG gene are associated with stomach cancer susceptibility. We performed this hospital-based case-control study to evaluate the association of four potentially functional XPG polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C and rs873601G>A) with stomach cancer susceptibility. The four single nucleotide polymorphisms (SNPs) were genotyped in 692 stomach cancer cases and 771 healthy controls. Logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association of interest. Of the studied SNPs, XPG rs873601G>A polymorphism was found to significantly associate with stomach cancer susceptibility (AA versus GG/AG: OR = 1.31, 95% CI = 1.03-1.66, P = 0.027). Combined analysis of all SNPs revealed that the individuals with two of risk genotypes had a significantly increased stomach cancer risk (OR = 1.52, 95% CI = 1.13-2.06). In the stratification analysis, the association between the rs873601AA genotype and stomach cancer risk was observed in older group (>59 year), as well as patients with non-cardia stomach cancer. Further combined analysis indicated men, smokers, or non-drinkers more than one risk genotypes had a significantly increased stomach cancer risk. Our results indicate that XPG rs873601G>A polymorphism may be associated with the risk of stomach cancer. Further prospective studies with different ethnicities and large sample sizes are needed to validate our findings.


Asunto(s)
Proteínas de Unión al ADN/genética , Endonucleasas/genética , Predisposición Genética a la Enfermedad , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas/genética , Factores de Transcripción/genética , Anciano , Alelos , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Expresión Génica , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etnología , Neoplasias Gástricas/patología
10.
Environ Sci Technol ; 50(15): 8020-7, 2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27359107

RESUMEN

On the basis of our previous field survey, we postulate that the pattern and degree of zinc (Zn) isotope fractionation in the Zn hyperaccumulator Noccaea caerulescens (J. & C. Presl) F. K. Mey may reflect a relationship between Zn bioavailability and plant uptake strategies. Here, we investigated Zn isotope discrimination during Zn uptake and translocation in N. caerulescens and in a nonaccumulator Thlaspi arvense L. with a contrasting Zn accumulation ability in response to low (Zn-L) and high (Zn-H) Zn supplies. The average isotope fractionations of the N. caerulescens plant as a whole, relative to solution (Δ(66)Znplant-solution), were -0.06 and -0.12‰ at Zn-L-C and Zn-H-C, respectively, indicative of the predominance of a high-affinity (e.g., ZIP transporter proteins) transport across the root cell membrane. For T. arvense, plants were more enriched in light isotopes under Zn-H-A (Δ(66)Znplant-solution = -0.26‰) than under Zn-L-A and N. caerulescens plants, implying that a low-affinity (e.g., ion channel) transport might begin to function in the nonaccumulating plants when external Zn supply increases. Within the root tissues of both species, the apoplast fractions retained up to 30% of Zn mass under Zn-H. Moreover, the highest δ(66)Zn (0.75‰-0.86‰) was found in tightly bound apoplastic Zn, pointing to the strong sequestration in roots (e.g., binding to high-affinity ligands/precipitation with phosphate) when plants suffer from high Zn stress. During translocation, the magnitude of isotope fractionation was significantly greater at Zn-H (Δ(66)Znroot-shoot = 0.79‰) than at Zn-L, indicating that fractionation mechanisms associated with root-shoot translocation might be identical to the two plant species. Hence, we clearly demonstrated that Zn isotope fractionation could provide insight into the internal sequestration mechanisms of roots when plants respond to low and high Zn supplies.


Asunto(s)
Thlaspi/metabolismo , Zinc/metabolismo , Brassicaceae/metabolismo , Raíces de Plantas/metabolismo , Isótopos de Zinc/metabolismo
11.
Mol Cell Biochem ; 407(1-2): 77-87, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26033204

RESUMEN

Signaling through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, especially JAK2/STAT3, is involved in renal fibrosis. Fluorofenidone (FD), a novel pyridone agent, exerts anti-fibrotic effects in vitro and in vivo. Herein, we sought to investigate whether FD demonstrates its inhibitory function through preventing JAK2/STAT3 pathway. In this study, we examined the effect of FD on activation of rat renal interstitial fibroblasts, glomerular mesangial cells (GMC), and expression of JAK2/STAT3. Moreover, we explored the histological protection effects of FD in UUO rats, db/db mice, and phosphorylation of JAK2/STAT3 cascade. Our studies found that pretreatment with FD resulted in blockade of activation of fibroblast and GMC manifested by fibronectin (FN) and α-smooth muscle actin (α-SMA) protein expression and decline of STAT3 tyrosine phosphorylation induced by IL-6 or high glucose. In unilateral ureteral obstruction rats and a murine model of spontaneous type 2 diabetes (db/db mice), treatment with FD blocked the expression of FN and α-SMA, prevented renal fibrosis progression, and attenuated STAT3 activation. However, FD administration did not interfere with JAK2 activation both in vivo and in vitro. In summary, the molecular mechanism by which FD exhibits renoprotective effects appears to involve the inhibition of STAT3 phosphorylation.


Asunto(s)
Enfermedades Renales/enzimología , Enfermedades Renales/prevención & control , Piridonas/administración & dosificación , Factor de Transcripción STAT3/metabolismo , Animales , Línea Celular , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Enfermedades Renales/genética , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Ratones , Fosforilación/efectos de los fármacos , Piridonas/farmacología , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/genética
12.
Clin Exp Pharmacol Physiol ; 41(7): 482-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24739055

RESUMEN

The aim of the present study was to investigate Toll-like receptor-4 (TLR4) signalling at different stages of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat, high-fructose (HFHFr) diet in mice. Both TLR4 wild-type (WT) and mutant (TLR4(mut) ) mice were fed either standard chow (SC) or the HFHFr diet for different periods of time from 4 to 16 weeks. Pathological characteristics and function of the liver were assessed. Simple steatosis, steatohepatitis and hepatic fibrosis occurred sequentially in Week 4, 8 and 16 in WT mice fed with the HFHFr. Expression of TLR4, myeloid differentiation factor 88 (MyD88), interferon regulatory factor (IRF) 3 and IRF7 started to increase at Week 4, peaked at Week 8 and then declined to basal levels at Week 16. This pattern was consistent with changes in inflammation in the liver revealed by haematoxylin and eosin staining. However, lipid accumulation, inflammation and fibrosis in livers of TLR4(mut) mice fed the HFHFr diet were significantly alleviated. In addition, the expression of activin A in WT mice fed the HFHFr diet increased at Week 16. The data suggest that TLR4 signalling mediates non-alcoholic steatohepatitis before fibrosis and that activin A is subsequently involved in NAFLD.


Asunto(s)
Grasas de la Dieta/toxicidad , Sacarosa en la Dieta/toxicidad , Fructosa/toxicidad , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Receptor Toll-Like 4/metabolismo , Activinas/genética , Activinas/metabolismo , Animales , Grasas de la Dieta/administración & dosificación , Sacarosa en la Dieta/administración & dosificación , Fructosa/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Factor 3 Regulador del Interferón/genética , Factor 3 Regulador del Interferón/metabolismo , Factor 7 Regulador del Interferón/genética , Factor 7 Regulador del Interferón/metabolismo , Ratones , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Transducción de Señal , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
13.
Int J Mol Sci ; 15(3): 3729-45, 2014 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-24595237

RESUMEN

Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF) which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs) strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer.


Asunto(s)
Movimiento Celular , Proliferación Celular , Factor de Crecimiento de Hepatocito/metabolismo , Células Madre Mesenquimatosas/metabolismo , Adenoviridae/genética , Animales , Apoptosis , Western Blotting , Línea Celular Tumoral , Células Cultivadas , Técnicas de Cocultivo , Expresión Génica , Vectores Genéticos/genética , Células HEK293 , Factor de Crecimiento de Hepatocito/genética , Humanos , Neoplasias Pancreáticas/patología , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción Genética
14.
J Dent Sci ; 18(4): 1651-1662, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37799896

RESUMEN

Background/purpose: Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Materials and methods: Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. Results: We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo, and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. Conclusion: Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.

15.
Food Sci Nutr ; 11(1): 504-515, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36655078

RESUMEN

Obesity has become a significant global public health problem. Functional drinks have been an essential direction for obesity prevention research. The present study investigated the preventive effect and safety of winter melon and lotus leaf Tibetan tea (WLTT, a compound tea drink based on Ya'an Tibetan Tea and medicine food homology herbs) on obesity. The rats' hypercaloric high-fat diet (HFD) obesity model was established to evaluate obesity prevention and explored the mechanism through intestinal flora regulation. The results showed that in obese rats with the intervention of WLTT (400, 800, and 1600 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels, and antioxidant enzyme activity (SOD, GSH-Px, and MDA) were progressively improved. 16S rRNA high-throughput sequencing showed that WLTT could improve intestinal flora disorders due to HFD, which significantly reversed the relative abundance of Firmicutes and the F/B ratio associated with an HFD, and significantly upregulated the relative abundance of Verrucomicrobia. At the genus level, the downregulation of the relative abundance of Akkermansia and unclassified_Lachnospiraceae groups, and the upregulation of the relative abundance of Romboutsia, Ruminococcus, Corynebacteriume, and Saccharibacteria_genera_incertae_sedis groups brought about by the HFD were significantly reversed. The results of the above experiments were compared favorably with those of a parallel experiment with Bi -Sheng -Yuan slimming tea (BSY, a functional drink based on green tea and medicine food homology herbs). Overall, the findings have provided that WLTT can prevent obesity owing to an HFD by regulating intestinal flora and has a good safety profile, and combinations of Tibetan tea and medicine food homology herbs could be a new option for obesity prevention.

16.
Virus Genes ; 44(3): 488-94, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22286609

RESUMEN

The genome of Banana bunchy top virus (BBTV) consists of six segments of single-stranded DNA of approximately 1 kb in length. We identified and sequenced the complete genomes of two BBTV isolates, one with and one without satellite DNA, from Haikou, Hainan, China. The Haikou-2 isolate contains six genomic segments and an additional satellite DNA while the Haikou-4 isolate contains only six genomic segments. Typical of other babuviruses, each genomic segment encodes a single open reading frame and contains the highly conserved stem-loop and major common regions. Phylogenetic analysis of the two Haikou isolates together with existing sequence records in GenBank confirmed the grouping of BBTV into two large groups and further refined the geographical distribution of each group. To accommodate the changes in the BBTV geographical distribution, the two groups are proposed as the Southeast Asian group and the Pacific-Indian Oceans group. Both the Haikou-2 and Haikou-4 isolates belong to the newly proposed Southeast Asian group.


Asunto(s)
Babuvirus/genética , Babuvirus/aislamiento & purificación , Clonación Molecular , ADN Viral/química , ADN Viral/genética , Genoma Viral , Babuvirus/clasificación , China , Análisis por Conglomerados , Datos de Secuencia Molecular , Musa/virología , Filogenia , Enfermedades de las Plantas/virología , Análisis de Secuencia de ADN
17.
World J Clin Cases ; 10(14): 4661-4668, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35663055

RESUMEN

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Papillary thyroid microcarcinoma (PTMC) accounts for the majority of PTC cases. However, concurrent pulmonary and hepatic metastases of PTMC are rarely seen. Here, we present a patient with coexisting liver and lung metastases from PTMC. CASE SUMMARY: We describe a 26-year-old woman with PTMC with multiple concurrent metastases. After 3 d of unexplained fever, she was admitted to our hospital. Her thyroid functional tests were abnormal. Her positron emission tomography (PET)/magnetic resonance imaging (MRI) examination showed increased fluorodeoxyglucose (FDG) metabolism and space-occupying lesions in the left lobe of the thyroid. Additionally, PET/MRI images revealed multiple nodules in the lung and liver with increased FDG metabolism. Chest computer tomography (CT) showed multiple pulmonary metastases. Abdominal ultrasound and liver MRI showed multiple space-occupying lesions in the liver. The patient underwent total thyroidectomy and central lymph node dissection. Postoperative pathological analysis showed a papillary microcarcinoma multiplex in the left lobe of the thyroid. A diagnosis of hepatopulmonary metastases from papillary thyroid microcarcinoma was made. The patient was given iodine-131 treatment one year after the surgery. She recovered well after the operation, and the incision healed well. After discharge, she was treated with oral levothyroxine sodium tablets, and symptomatic and supportive treatments were also given to promote radioactive excretion and prevent bone marrow suppression by iodine-131 treatment. CONCLUSION: Since patients with thyroid cancer concurrent with hepatopulmonary metastases have rarely been reported, our case will highlight the clinical and pathological profiles of these patients.

18.
Sci Total Environ ; 822: 153304, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35090923

RESUMEN

Basalt-derived soils are widespread worldwide. Such soils contain high levels of heavy metals like chromium (Cr), which is a serious environmental concern. However, little is known regarding the enrichment and speciation of Cr during the basalt weathering process. Therefore, two basalt-derived soil profiles (Nitisol and Ferralsol) in the Leizhou Peninsula, south tropical China, were investigated to explore the redistribution and transformation of Cr during basalt weathering. All profiles could be divided into three layers: rocks, saprolites, and soils. The Nitisol and Ferralsol profiles exhibited strong (kaolinization) and extreme (laterization) degrees of weathering, respectively. Results showed that Cr concentrations in the saprolites (234 to 315 mg·kg-1) were higher than those in basalt rocks (139 to 159 mg·kg-1), indicating that Cr was enriched with the continuous loss of Si and other mobile macro-elements. While high levels of Cr were also enriched in the soils (178 to 430 mg·kg-1) accompanied with Fe. However, in the upper soils of the Ferralsol profile, the acidity and organic matter could promote the leaching of Cr. Geochemical fractions and EPMA mapping showed that chromite and olivine were the main Cr-bearing minerals in basalt, but Fe-oxides (e.g., goethite and hematite) contained the highest portion of Cr in weathered saprolites and soils. The availability of Cr in the soil was extremely low due to the high stability of Cr bound to Fe-oxides. However, the decreasing contents of Cr bound to Fe-oxides in the upper soils of the Ferralsol profile indicated that Cr could also be released during Fe leaching. In conclusion, the weathering of basalt can lead to the enrichment of Cr in Fe-(hydro)oxides, which are the main controlling minerals for Cr mobility in basalt-derived soils. Further research is needed to evaluate the effect of Fe-(hydro)oxide formation and dissolution on the release of soil Cr.


Asunto(s)
Cromo , Contaminantes del Suelo , China , Cromo/análisis , Monitoreo del Ambiente , Silicatos , Suelo/química , Contaminantes del Suelo/análisis
19.
Chemosphere ; 276: 130212, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33740654

RESUMEN

Rice as a paddy field crops, iron-containing materials application could induce its iron plaque formation, thereby affecting cadmium (Cd) transportation in the rhizosphere and its uptake in root. In this study, a hydroponic experiment was conducted to investigate the effects of three exogenous iron materials, namely nano-Fe3O4-modified biochar (BC-Fe), chelated iron (EDTA-Fe), and ferrous sulfate (FeSO4), on the iron plaque formation on the surface of rice root, and to investigate the effects of formed iron plaque on the absorption, migration, and transportation of Cd and Fe in rice plant. The results showed that yellow-brown and brown iron plaque was formed on surface cells of the Fe-treated rice root, and some black particles were embedded in the iron plaque formed by BC-Fe. The proportion of crystallized iron plaque (31.8%-35.9%) formed by BC-Fe was much higher than that formed by EDTA-Fe and FeSO4. The Cd concentrations in the crystallized iron plaque formed by BC-Fe were 7.64-13.0 mg·kg-1, and increased with the increasing of Fe concentrations in the plaque. The Cd translocation factor from root to stem (TFr-s) and the Cd translocation factor from stem to leaf (TFs-l) with BC-Fe treatment decreased by 84.7% and 80.0%, respectively. The results demonstrated that application BC-Fe promoted the formation of iron plaque and enhanced the sequestration of Cd and Fe in roots, thus reduced the transportation and accumulation of Cd in aerial rice tissues.


Asunto(s)
Oryza , Contaminantes del Suelo , Cadmio/análisis , Carbón Orgánico , Hierro/análisis , Raíces de Plantas/química , Suelo , Contaminantes del Suelo/análisis
20.
Artículo en Inglés | MEDLINE | ID: mdl-32981877

RESUMEN

OBJECTIVES: The aim of this study was to retrospectively analyze the clinical characteristics, surgical treatment, and prognosis of patients with diffuse-type tenosynovial giant cell tumor (D-TGCT) involving the temporomandibular joint (TMJ) and the skull base. STUDY DESIGN: A retrospective study was performed in patients with D-TGCT involving the TMJ and the skull base at our institute from April 2009 to August 2018. Data on clinical characteristics, surgical treatment, and prognosis were collected and analyzed. A literature search on D-TGCT involving the TMJ was conducted and the data analyzed. RESULTS: The study included 22 patients (14 males and 8 females), with an average age of 44 years. The main symptoms were headache and hearing limitation, accompanied by a swelling in the TMJ area. Magnetic resonance imaging (MRI) showed low signals on T1- and T2-weighted images. All lesions were completely removed. Temporal bone flap, titanium mesh, and temporal muscle flap were used for reconstruction. The recurrence rate was 4.5%. In the literature, 115 cases were reported. Surgery alone was performed in 88 cases; postoperative radiotherapy was performed in 19 cases; the tumor recurrence rates were 9.1% and 15.8% for the 2 procedures, respectively. All patients were alive at the end of the follow-up period. CONCLUSIONS: D-TGCT involving the TMJ and the skull base is a locally aggressive but benign lesion necessitating complete resection and has a good prognosis.


Asunto(s)
Tumor de Células Gigantes de las Vainas Tendinosas , Recurrencia Local de Neoplasia , Adulto , Femenino , Tumor de Células Gigantes de las Vainas Tendinosas/diagnóstico por imagen , Tumor de Células Gigantes de las Vainas Tendinosas/cirugía , Humanos , Masculino , Estudios Retrospectivos , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/cirugía , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/cirugía
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