RESUMEN
Inguinal hernia develops primarily in elderly men, and more than one in four men will undergo inguinal hernia repair during their lifetime. However, the underlying mechanisms behind hernia formation remain unknown. It is known that testosterone and estradiol can regulate skeletal muscle mass. We herein demonstrate that the conversion of testosterone to estradiol by the aromatase enzyme in lower abdominal muscle (LAM) tissue causes intense fibrosis, leading to muscle atrophy and inguinal hernia; an aromatase inhibitor entirely prevents this phenotype. LAM tissue is uniquely sensitive to estradiol because it expresses very high levels of estrogen receptor-α. Estradiol acts via estrogen receptor-α in LAM fibroblasts to activate pathways for proliferation and fibrosis that replaces atrophied myocytes, resulting in hernia formation. This is accompanied by decreased serum testosterone and decreased expression of the androgen receptor target genes in LAM tissue. These findings provide a mechanism for LAM tissue fibrosis and atrophy and suggest potential roles of future nonsurgical and preventive approaches in a subset of elderly men with a predisposition for hernia development.
Asunto(s)
Músculos Abdominales/patología , Estradiol/metabolismo , Fibrosis/patología , Hernia Inguinal/patología , Atrofia Muscular/metabolismo , Testosterona/metabolismo , Animales , Aromatasa/metabolismo , Receptor alfa de Estrógeno , Regulación Enzimológica de la Expresión Génica , Masculino , Ratones , Ratones Transgénicos , Modelos Animales , Músculo Esquelético/patología , Atrofia Muscular/patología , Receptores AndrogénicosRESUMEN
OBJECTIVE: This retrospective study investigated the clinical and radiographic outcomes following temporary transpedicular posterior instrumentation between two cohorts of patients with thoracolumbar fractures (TLF) who underwent selective or bi-segments intervertebral articular process fusion. METHODS: Patients with TLF who underwent the temporary posterior fixation with selective fusion (Group SF), or bi-segments fusion (Group BF) were studied. Superior intervertebral articular process and interlaminar fusion were performed in Group SF, whereas in Group BF, the patients underwent bi-segments fusion in both superior and inferior articular processes, as well as interlaminar fusion. We measured the distal and proximal intervertebral mobility, regional kyphotic angle, and vertebral height before and after surgery in both groups. Greenough Low-Back Outcome Score was used to assess the clinical outcomes. RESULTS: Sixty-five patients with TLF from T12 to L2 fractures were enrolled in the study period: 33 patients in the Group SF and 32 patients in the Group BF. All the patients experienced fracture healing (mean follow-up time: 19.7 months). The mean postoperative functional outcomes were 65.0 ± 2.0 points for the Low-Back Outcome Score in the Group SF and 65.2 ± 1.8 for the Group BF. A progressive regional kyphotic angle was observed with time regardless of fusion but was not significantly different between the two groups. There was a statistical difference between unfused inferior proximal adjacent and inferior distal adjacent segment regardless of fracture segments. CONCLUSIONS: The strategy of selective fusion is reported to be useful for the treatment of patients with TLF. The motion in the un-fused and adjacent segment could be better regained after instrumentation removal in the selective fusion group. LEVEL OF EVIDENCE: Level 3.
RESUMEN
BACKGROUND This retrospective clinical study aimed to compare the efficacy of preoperative halo-gravity traction with postoperative halo-femoral traction after posterior spinal release in corrective surgery for patients with severe kyphoscoliosis. MATERIAL AND METHODS A retrospective clinical study included patients who underwent elective corrective surgery for severe kyphoscoliosis (N=60) between 2013 and 2015. Two patient groups were compared, the postoperative halo-femoral traction after posterior spinal release (R-HF) group (N=30) and the preoperative halo-gravity traction (HGT) group (N=30). Demographic and clinicopathological data included age, gender, Cobb angle, degree of spinal curvature, history of osteotomy, and etiological factors. Patients in the two study groups were matched. Postoperative surgical outcome was evaluated by the radiographic coronal Cobb angle, global kyphosis, coronal balance, and the sagittal vertical axis (SVA). Clinical outcome was assessed using the Scoliosis Research Society Outcomes Questionnaire (SRS-22). RESULTS The preoperative Cobb angle was similar between the R+HF group and the HGT group (123.5±12.7° vs. 123.1±14.1°; P=0.909). Following postoperative traction, a significantly higher correction rate was found in the R+HF group than the HGT group (31.8±7.8% vs. 19.3±12.9%; P=0.001). The postoperative correction rate in the R+HF group was significantly higher than the HGT group (44.7±7.8% vs. 39.0±12.8%; P=0.042). In both study groups, the postoperative SRS-22 scores were significantly improved with no statistical difference between the two groups, and no neurological complications occurred. CONCLUSIONS Patients with severe kyphoscoliosis who underwent postoperative halo-femoral traction after posterior spinal release achieved satisfactory radiographic correction.
Asunto(s)
Fémur/cirugía , Gravitación , Cifosis/cirugía , Cuidados Preoperatorios , Escoliosis/cirugía , Columna Vertebral/cirugía , Tracción , Adolescente , Adulto , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Humanos , Cifosis/diagnóstico por imagen , Cifosis/patología , Masculino , Periodo Posoperatorio , Estudios Retrospectivos , Escoliosis/diagnóstico por imagen , Escoliosis/patología , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: Liver injury triggers a highly organized and ordered liver regeneration (LR) process. Once regeneration is complete, a stop signal ensures that the regenerated liver is an appropriate functional size. The inhibitors and stop signals that regulate LR are unknown, and only limited information is available about these mechanisms. METHODS: A 70% partial hepatectomy (PH) was performed in hepatocyte-specific PP2Acα-deleted (PP2Acα(-/-)) and control (PP2Acα(+/+)) mice. LR was estimated by liver weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were analyzed. RESULTS: We found that the catalytic subunit of PP2A was markedly upregulated during the late stage of LR. PP2Acα(-/-) mice showed prolonged LR termination, an increased liver size compared to the original mass and lower levels of serum ALT and AST compared with control mice. In these mice, cyclin D1 protein levels, but not mRNA levels, were increased. Mechanistically, AKT activated by the loss of PP2Acα inhibited glycogen synthase kinase 3ß (GSK3ß) activity, which led to the accumulation of cyclin D1 protein and accelerated hepatocyte proliferation at the termination stage. Treatment with the PI3K inhibitor wortmannin at the termination stage was sufficient to inhibit cyclin D1 accumulation and hepatocyte proliferation. CONCLUSIONS: PP2Acα plays an essential role in the proper termination of LR via the AKT/GSK3ß/Cyclin D1 pathway. Our findings enrich the understanding of the molecular mechanism that controls the termination of LR and provides a potential therapeutic target for treating liver injury.
Asunto(s)
Ciclina D1/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hepatocitos/metabolismo , Regeneración Hepática/fisiología , Proteína Fosfatasa 2/metabolismo , Animales , Apoptosis/fisiología , Proliferación Celular/fisiología , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Patients with mucopolysaccharidoses IVA (MPS IVA) have a progressive accumulation of the specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS), leading to the degeneration of the cartilage matrix and its connective tissue perturbing the regular microarchitecture of cartilage and successively distorting bone ossification and growth. Impaired cartilage quality and poor bone mineralization lead to serious hip disorders in MPS IVA patients. Although hip dysplasia is seen widely in musculoskeletal abnormality of this disorder, the pathophysiology of the hip bone and cartilage morphology in these patients remains unclear. Until now, no systemic study of the hip joints in MPS IVA has been reported by using the combined images of plain film radiographs (PFR) and Magnetic Resonance Imaging (MRI). This study aimed to assess the bony and cartilaginous features of hip joints and to explore the potentially related factors of femoral head osteonecrosis (FHN) and hip subluxation/dislocation in patients with MPS IVA. Hip joints in MPS IVA patients were retrospectively reviewed, based on the findings of PFR and MRI data from 2014 to 2019. Demographic information was also collected and analyzed with imaging measurements. A total of 19 patients (eight boys and 11 girls) were recruited, and 38 hip joints in these patients were examined. Eleven patients (57.9%) had FHN. FHN patients were statistically compared with those without FHN. Correlations between cartilaginous femoral head coverage (CFHC) and acetabular index (AI), cartilaginous AI (CAI), or neck-shaft angle (NSA) were investigated in patients with hip subluxation or dislocation. The greater cartilaginous coverage of the hips than their osseous inherency was observed. Significant correlation was observed between CFHC and AI (r =-0.351, p = 0.049) or CAI (r =-0.381, p = 0.032). Severe subluxations or dislocations were more likely to be present in those with more dysplastic bony and cartilaginous hips. In conclusion, our study provides the first systemic description of bony and cartilaginous characteristics in the hip morphology of MPS IVA patients. We have demonstrated that plain radiography alone leads to a misunderstanding of hip morphology and that MRI measurements with PFR are an essential tool to evaluate the 'true' characterization of hips for MPS IVA patients.
RESUMEN
BACKGROUND: Atlantoaxial instability owing to bone erosions in a patient with ankylosing spondylitis (AS) is rare. We describe the radiographic characteristics, pathology, and treatment of a patient with this rare clinical manifestation and review the literature. CASE DESCRIPTION: A 36-year-old man with an 8-year history of AS presented with progressive neck pain, low back pain, hand numbness, and limited mobility of the neck. Cervical radiography showed anterior atlantoaxial subluxation with bone erosions at the odontoid process and a mass lateral to the atlas and edge of vertebrae. AS was diagnosed according to the modified New York criteria, and the patient underwent a posterior C0-C6 occipitocervical arthrodesis surgery and C3-C6 laminectomy to reconstruct atlantoaxial stability and relieve cervical compression. The symptoms of neck pain and hand numbness improved at the 1-year follow-up, and the patient completely resumed normal activities. Imaging showed realignment of C1-2 with complete decompression of the spinal cord and fusion of the atlantooccipital joint. The internal fixation has remained stable, and progressive bone erosion changes were not found after surgery. CONCLUSIONS: Extensive cervical erosions with spontaneous atlantoaxial subluxation in AS is extremely rare. The erosive change of atlantoaxial bone may be an early feature of AS. Cervical spine radiographs are essential for patients with AS who present with neck pain. Complete decompression and internal fixation are necessary to prevent serious neurologic morbidity from spinal cord injury in such patients.
Asunto(s)
Articulación Atlantoaxoidea/diagnóstico por imagen , Articulación Atlantoaxoidea/cirugía , Atlas Cervical/diagnóstico por imagen , Atlas Cervical/cirugía , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/cirugía , Adulto , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Masculino , Dolor de Cuello/diagnóstico por imagen , Dolor de Cuello/etiología , Espondilitis Anquilosante/complicacionesRESUMEN
BACKGROUND: Scoliosis secondary to lumbar disc herniation (LDH) may occur in both adolescents and adults. As the spine is more flexible in adolescents than in adults, the curve features and curve evolution could be different between these 2 cohorts, which were unclear. OBJECTIVES: To compare the radiologic features of scoliosis secondary to LDH between adolescents and adults, and to further characterize the curve evolution after lumbar discectomy in 2 cohorts. STUDY DESIGN: A retrospective study. SETTING: An inpatient surgery center. METHODS: Patients with scoliosis secondary to LDH who underwent surgical intervention between 2010 and 2016 were reviewed. Radiographic parameters were measured on standing whole spine radiographs. The apical vertebral translation was measured on serial radiographs taken before surgery, one month and 6 months after surgery, and at last follow-up to evaluate the curve evolution. Meanwhile, the patients' reported outcomes were evaluated. According to age, patients were divided into adolescent and adult group. Comparisons between the 2 groups were made with regards to the preoperative and postoperative radiographic parameters and clinical outcomes. RESULTS: A total of 42 adolescent and 41 adult patients were included in this study. The incidence of scoliosis secondary to LDH in the adolescents was significantly higher than that in the adults. Adolescent patients present remarkably higher incidence of coronal balance as compared with the adult patients preoperatively. No significant difference was observed between the 2 groups in terms of preoperative radiographic parameters. A total of 85.7% of the adolescent patients and 92.7% of the adult patients achieved resolution of scoliosis within 6 months after surgery. LIMITATIONS: This was a retrospective study with a small series of cases and relatively short-term follow-up. CONCLUSIONS: The incidence of scoliosis secondary to LDH in adolescents is significantly higher than in adults. Moreover, adolescent patients are more likely to present coronal balance before surgery. The 2 cohorts could have comparable curve evolution, and resolution of scoliosis generally occurred within 6 months after surgery. KEY WORDS: Sciatic scoliosis, lumbar disc herniation, adolescent, adult, resolution, lumbar discectomy.
Asunto(s)
Discectomía/efectos adversos , Vértebras Lumbares/cirugía , Escoliosis , Adolescente , Femenino , Humanos , Incidencia , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Masculino , Radiografía , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Osteoarthritis (OA) is usually recognized to have a genetic factor, and in our study, we performed a case-control study to analyze the association between 14 single nucleotide polymorphisms (SNPs) in OPG and the risk of knee OA in a Chinese Han population. METHODS: Fourteen OPG SNPs were assayed using MassARRAY in 393 patients clinically and radiographically diagnosed with knee OA and in 500 controls. Allelic and genotypic frequencies were compared between the groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: We found that the minor alleles of six SNPs in OPG were associated with an increased or decreased risk of knee OA in the allelic model analysis. In the genetic model analysis, we found that rs1905786, rs1032128, rs3134058, rs11573828, rs11573849, rs3134056, and rs1564861 were associated with an increased or decreased risk of knee OA before adjusted by sex and age. And after adjustment, three SNPs (rs1485286, rs1905786, and rs1032128) were identified to have a negative effect on knee OA. CONCLUSION: Our results verify that genetic variants of OPG contribute to knee OA susceptibility in the population of northern China. These genetic associations may identify individuals at a particularly high risk of developing knee OA.
Asunto(s)
Osteoartritis de la Rodilla/genética , Osteoprotegerina/genética , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Osteoprotegerina/metabolismo , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
Hepatic stellate cells (HSCs) play a critical role in the pathogenesis and reversal of liver fibrosis. Targeting HSCs is of great significance in the treatment of hepatic fibrosis, and has attracted wide attention of scholars. Here we demonstrated that expression of geranylgeranyldiphosphate synthase (GGPPS) predominantly increased in HSCs in murine fibrotic liver. HSC-specific knockdown of GGPPS using vitamin A-coupled liposome carrying siRNA-ggpps decreased activation of HSCs and alleviated fiber accumulation in vivo. Furthermore, our in vitro studies showed that GGPPS was up-regulated during HSCs activation in TGF-ß1-dependent manner. Inhibition of GGPPS suppressed TGF-ß1 induced F-actin reorganization and HSCs activation in LX-2 cells. Further, we found that GGPPS regulated HSCs activation and liver fibrosis possibly by enhancing RhoA/Rock kinase signaling. So its concluded that GGPPS promotes liver fibrosis by activating HSCs, which may represent a potential target for anti-fibrosis therapies.
RESUMEN
In this study, the first complete mitochondrial genome of Lindian Chicken (Gallus gallus) was sequenced in order to develop the mitogenome data for genus gallus. The complete mitogenome sequence is 16,785 bp in length, containing 37 genes (13 protein-coding genes, 2 ribosomal RNA, 22 transfer RNA genes, and one control region). The new sequenced complete mitogenome of Lindian Chicken will provide useful information for application in conservation genetics and evolution for this Near Threatened Chicken genomes.
RESUMEN
OBJECTIVE: The aim of this study was to prospectively compare the radiographic and clinical outcomes between the posterior fossa decompression (PFD) and PFD with duraplasty (PFDD) procedures in adolescent patients with Chiari malformation type I (CMI). METHODS: Ninety adolescent patients with CMI were randomly assigned to undergo either PFDD or PFD. In both groups, a dissection from the occipital bone was performed. The dura was not opened in the PFD group, and the outer layer of dura was resected. However, in the PFDD group, the dura mater was opened and expanded. Data were analyzed for clinical outcome, complications, and syrinx resolution. RESULTS: The age, gender, and preoperative neurologic status were similar between the 2 groups. Compared with the PFD group, patients undergoing PFDD had significantly longer operation time, longer postoperative drainage time, and higher drainage volume. At the latest follow-up, no statistically significant difference was found between the 2 groups in terms of syrinx resolution. The clinical outcomes were similar in the PFDD and PFD group. Compared with the PFD group, patients in the PFDD group had a higher incidence of cerebrospinal fluid leak. CONCLUSIONS: Compared with the more aggressive decompression with duraplasty, PFD without duraplasty produces comparable radiologic and clinical outcomes and is associated with a lower risk of complications.
Asunto(s)
Malformación de Arnold-Chiari/diagnóstico por imagen , Malformación de Arnold-Chiari/cirugía , Descompresión Quirúrgica/métodos , Duramadre/diagnóstico por imagen , Duramadre/cirugía , Adolescente , Malformación de Arnold-Chiari/fisiopatología , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Complicaciones Posoperatorias , Resultado del TratamientoRESUMEN
A transposon is a DNA segment, which is able to change its relative position within the entire genome of a cell. The piggyBac (PB) transposon is a movable genetic element that efficiently transposes between vectors and chromosomes through a "cut-and-paste" mechanism. During transposition, the PB transposase recognizes transposon-specific inverted terminal repeats (ITRs) sequences located on both ends of the transposon vector and eight efficiently moves the contents from its original positions and efficiently integrates them into TTAA chromosomal sites. PB has drawn much attention because of its transposition efficiency, safety and stability. Due to its priorities, PB can be used as a new genetic vehicle, a new tool for oncogene screening and a new method for gene therapy. PB has created a new outlook for human gene encoding.
RESUMEN
Liver cancer is a common cancer and a leading cause of cancer-related deaths. Among all types of primary liver cancers, hepatocellular carcinoma (HCC) is the major histological subtype, and hepatitis B virus (HBV) infection is the leading cause of HCC. Treatments for hepatitis B related HCC include hepatectomy, liver transplantation, transarterial chemoembolization (TACE), ablative therapy, and Sorafenib treatment. However, HBV reactivation can occur in patients who receive these treatments, resulting in poor clinical outcomes. However, prophylactic antiviral treatment in patients with hepatitis B-related HCC, can reduce the copies of HBV DNA, prevent HBV reactivation, reduce hepatic inflammation, reverse liver fibrosis, decrease tumor recurrence and metastasis, and extend survival time. Prophylactic antiviral treatment should be routinely performed as an important adjuvant therapy in HBV-related HCC patients.
Asunto(s)
Antivirales/administración & dosificación , Carcinoma Hepatocelular/terapia , Hepacivirus/efectos de los fármacos , Hepatitis B/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Activación Viral/efectos de los fármacos , Animales , Antivirales/efectos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virología , Progresión de la Enfermedad , Esquema de Medicación , Hepacivirus/genética , Hepacivirus/crecimiento & desarrollo , Hepatitis B/diagnóstico , Hepatitis B/virología , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virología , Recurrencia , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Tumor dormancy is one of the stages in tumor development without clinical symptoms. Tumor dormant cells may appear in early stages of tumor development, as well as in micrometastasis and minimal residual disease. The mechanism for the switch of dormant cells between quiescent and proliferative stages is still largely unknown. Potential mechanisms that may account for the transition between dormant tumor cells and proliferative cells include angiogenesis, immune response, cellular factors, and signaling pathways. The clinical and therapeutic importance of dormant cells requires further studies to provide therapeutic strategies for inhibition of metastasis and tumor recurrence.
Asunto(s)
Recurrencia Local de Neoplasia/patología , Neoplasias/patología , Animales , Proliferación Celular , Humanos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/metabolismo , Neoplasias/inmunología , Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Transducción de SeñalRESUMEN
Aromatase inhibitors (AIs) are the most effective endocrine treatment for estrogen receptor α-positive (ERα+) postmenopausal breast cancer. Identification of biomarkers that are able to predict AIs responsiveness of patients is a key for successful treatment. The currently used biomarkers for tamoxifen responsiveness, which including ERα as well as progesterone receptor can only predict part of the potential responders to AIs treatment. Sushi domain-containing protein 3 (SUSD3) is a potential novel biomarker of AIs responsiveness. The lack of SUSD3 expression in breast cancer tissue can be an important predictor for non-responsiveness to AI. Here we reviewed the property and function of SUSD3, its usage as a biomarker and the practicability for SUSD3 to become a target for immune therapy. We suggest this protein can be potentially measured or targeted for prevention, diagnostic, and therapeutic purposes for estrogen or progesterone-dependent disorders including breast cancer in women.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia , Proteínas de la Membrana/inmunologíaRESUMEN
BACKGROUND: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domaincontaining protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation betweenthe two proteins. MATERIALS AND METHODS: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. RESULTS: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normalbreast tissue (P<0.05) .The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r= 0.553, P<0.01). CONCLUSIONS: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Proteínas de la Membrana/metabolismo , Receptor IGF Tipo 1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Receptor alfa de Estrógeno/metabolismo , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-2/metabolismoRESUMEN
BACKGROUND: Crocin is the major constituent of saffron, a naturally derived Chinese medicine obtained from the dried stigma of the Crocus sativus flower. It has a variety of pharmacological effects, including anti-oxidative, immunity enhancement, and anti-tumorigenic properties; however, the molecular mechanisms underlying these effects remain unknown. METHODS: To investigate the effects of crocin on proliferation and apoptosis of lung adenocarcinoma cells, lung adenocarcinoma cell lines, A549 and SPC-A1, were treated with crocin at different dosages. Cell morphological changes were observed by light microscopy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the inhibitory effect of crocin on cell proliferation and sensitivity to chemotherapeutic drugs. Flow cytometry was used to characterize cell apoptosis and cell cycle profiles. Reverse transcription-polymerase chain reaction was used to detect mRNA levels of apoptosis-related genes. RESULTS: Crocin inhibited cell proliferation and induced apoptosis in A549 and SPC-A1 cells in a concentration-dependent manner, accompanied with an increase of G0/G1 arrest. Crocin significantly increased the mRNA levels of both p53 and B-cell lymphoma 2-associated X protein (Bax), while decreasing B-cell lymphoma 2 (Bcl-2) mRNA expressions. In addition, crocin combined with either cisplatin or pemetrexed showed additive effects on cell proliferation in two lung cancer cell lines. CONCLUSIONS: Crocin significantly suppressed the proliferation of human lung adenocarcinoma cells and enhanced the chemo sensitivity of these cells to both cisplatin and pemetrexed. The actions of molecular mechanism could be through the induction of cell cycle arrest and apoptosis by p53 and Bax up-regulation but Bcl-2 down-regulation.
RESUMEN
Abstract Rabbit with hypercholesterolaemia is an important model for studying cholesterol metabolism disease. This study aimed to evaluate the expression stability of nine reference genes for quantitative PCR (qPCR) analysis in adrenal gland, liver, spleen, and kidney tissue from rabbits with hypercholesterolaemia. In total, 30 male Harbin Large White (HLW) rabbits were fed a normal feed (n = 15) or a high cholesterol feed (n = 15) for 8 weeks to induce hypercholesterolaemia. Nine reference genes were verified by qPCR using cDNA extracted from rabbit tissue samples. For qPCR analysis, reference genes were evaluated using the RefFinder and GeNorm algorithms. Overall, seven rabbits with hypercholesterolaemia were identified based on body weight and total cholesterol measurements. Combining the results of the RefFinder and GeNorm algorithms, the most stable reference genes were hypoxanthine phosphoribosyltransferase 1 (Hprt1) and eukaryotic translation elongation factor 1 alpha 1 (Eef1a1) in the adrenal gland, β-2-microglobulin (B2m) and glyceraldehyde-3-phosphate dehydrogenase (Gapdh) in the liver, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and Gapdh in the spleen, and peptidylprolyl isomerase (Ppia), β-actin (Actb), succinate dehydrogenase complex subunit A flavoprotein (Sdha), and B2m in the kidney. Taken together, our results confirmed that Hprt1 and Eef1a1, B2m and Gapdh, Ywhaz and Gapdh, and Ppia, Actb, Sdha, and B2m were the best reference genes for qPCR analyses in adrenal gland, liver, spleen, and kidney tissue, respectively, of rabbits with hypercholesterolaemia.