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1.
Antimicrob Agents Chemother ; 68(10): e0095924, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39171918

RESUMEN

Helicobacter pylori (H. pylori) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and H. pylori does not readily develop drug resistance. Through in vivo experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. After treatment with desoxyshikonin, colonization of H. pylori in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in H. pylori, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.


Asunto(s)
Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Pruebas de Sensibilidad Microbiana , Helicobacter pylori/efectos de los fármacos , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Antraquinonas/farmacología , Masculino , Biopelículas/efectos de los fármacos
2.
Mol Cell Biochem ; 479(1): 13-27, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36988779

RESUMEN

Cancer cells-derived exosomal lncRNAs could modulate the tumorigenesis of colorectal cancer (CRC) via modulating macrophage M2 polarization. However, the clarified mechanism and function of lncRNA BANCR in CRC remains unclear. Exosomes were identified by TEM, NTA, western blot and fluorescent staining. M2 macrophages were identified by CD206 and CD163 expressions using by flow cytometry and RT-qPCR. In addition, the relation between IGF2BP2 and BANCR or RhoA were explored by RIP assay. The malignant behaviors of CRC cells were examined by CCK-8, EdU and transwell assays. Histopathological changes in mice were observed by H&E staining. Silencing of BANCR notably inhibited the proliferation, migration and invasion of CRC cells. SW620 and HCT-15 cells-derived exosomal BANCR positively regulated the macrophage M2 polarization. In addition, exosomal BANCR remarkably enhanced the promoting roles mediated by M2 macrophages on proliferation and invasion in CRC cells. Meanwhile, exosomal BANCR promoted the M2 macrophage polarization via activation of RhoA/Rock pathway by recruiting IGF2BP2. Inhibition of RhoA/Rock pathway reversed exosomal BANCR-mediated macrophages M2 polarization and CRC malignant behaviors in SW620 and HCT-15 cells. Exosomal lncRNA BANCR derived from SW620 and HCT-15 cells promoted the metastasis of CRC via inducing the polarization of M2 macrophages. Thus, BANCR might be a new target for the treatment of CRC.


Asunto(s)
Neoplasias Colorrectales , Exosomas , MicroARNs , ARN Largo no Codificante , Animales , Ratones , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Exosomas/metabolismo , Macrófagos/metabolismo , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
3.
World J Urol ; 42(1): 44, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38244144

RESUMEN

PURPOSE: To develop and validate a low-cost homemade bench-top training model to facilitate retrograde intrarenal surgery (RIRS) training. METHODS: The RIRS training model (G-Model) was developed using a surgical glove and a recycled ureter access sheath. Fifteen participants including 10 residents and 5 urologists were enrolled. Designed training curriculum for residents was carried out. Face validity, content validity, construct validity and criterion validity evaluation of the G-Model were carried out. RESULTS: The global score of face and content validity was 4.15 ± 0.53 and 4.65 ± 0.29, respectively. For construct validity, the overall modified global rating scale (mGRS) score was significantly improved [12.5 (5.25) vs. 24.0 (5.25), p = 0.004], and the total task time was significantly shortened (39.5 ± 4.48 min vs. 24.1 ± 3.81 min, p < 0.001) within residents after G-Model training. The baseline mGRS score and total task time of residents were poorer than those of urologists [12.5 (5.25) vs. 32.0 (1.00), p < 0.001; 39.5 ± 4.48 min vs. 16.0 ± 1.58 min, p < 0.001]. Spearman correlation analysis revealed strong correlations between residents' G-Model and real patient performance. CONCLUSION: The current study presented a valid low-cost easily accessible RIRS bench-top training model which could facilitate skill acquisition and translate to real-life scenario.


Asunto(s)
Uréter , Ureteroscopía , Humanos , Ureteroscopía/educación , Urólogos , Curriculum , Modelos Anatómicos
4.
Artículo en Inglés | MEDLINE | ID: mdl-37944958

RESUMEN

Objective: Rising upper urinary tract calculus (UUTC) cases demand effective treatment. FUL, while efficient, poses infection risks and SIRS. This study explores CHR, NLR, and U-HBP as potential SIRS predictors post-FUL in UUTC patients, aiming to improve early detection and enhance SIRS management. Methods: A retrospective analysis was conducted on data from 216 UUTC patients who underwent FUL between April 2020 and April 2023. Occurrence of SIRS post-FUL was studied. Patients were categorized into SIRS and non-SIRS groups. CHR, NLR, and U-HBP levels were compared. Predictive value of CHR, NLR, and U-HBP for SIRS was assessed. Univariate and multivariate logistic regression analyses identified SIRS influencing factors. Results: In a study involving 216 patients undergoing Flexible Ureteroscopic Holmium Laser Lithotripsy (FUL), Systemic Inflammatory Response Syndrome (SIRS) occurred in 20.83% of cases. Patients with SIRS exhibited significantly elevated levels of C-reactive protein to High-density lipoprotein cholesterol ratio (CHR) (9.26 ± 2.17 vs. 3.89 ± 0.92), Neutrophil to Lymphocyte Ratio (NLR) (5.21 ± 0.98 vs. 2.62 ± 0.49), and Urinary Heparin Binding Protein (U-HBP) (3.01 ± 0.51 ng/L vs. 1.22 ± 0.19 ng/L) compared to the non-SIRS group. Multivariate analysis identified factors such as infected stones (OR = 3.294), stone size ≥ 30 mm (OR = 2.034), CHR ≥ 8.76 (OR = 4.554), NLR ≥ 3.74 (OR = 3.951), and U-HBP ≥ 1.55 ng/L (OR = 4.884) as significant predictors for SIRS. These findings emphasize the pivotal role of these biomarkers and stone characteristics in predicting inflammatory responses post-FUL surgery. Conclusion: This study establishes the predictive power of elevated C-reactive protein to High-density lipoprotein cholesterol ratio (CHR), Neutrophil to Lymphocyte Ratio (NLR), and Urinary Heparin Binding Protein (U-HBP) levels for Systemic Inflammatory Response Syndrome (SIRS) post Flexible Ureteroscopic Holmium Laser Lithotripsy (FUL) in upper urinary tract calculi patients. Stone characteristics, including infected stones and stone size ≥ 30 mm, are also key indicators of SIRS. These findings offer crucial insights for effective post-operative management, enhancing outcomes in urinary calculi treatment.

5.
BMC Surg ; 22(1): 384, 2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36348354

RESUMEN

BACKGROUND AND OBJECTIVE: The Cortical Bone Trajectory (CBT) technique provides an alternative method for fixation in the lumbar spine in patients with osteoporosis. An accuracy CBT screw placement could improve mechanical stability and reduce complication rates. PURPOSE: The purpose of this study is to explore the accuracy of cortical screw placement with the application of implanted spinous process clip (SPC) guide. METHODS AND MATERIALS: Four lumbar specimens with T12-S1 were used to access the accuracy of the cortical screw. The SPC-guided planning screws were compared to the actual inserted screws by superimposing the vertebrae and screws preoperative and postoperative CT scans. According to preoperative planning, the SPC guide was adjusted to the appropriate posture to allow the K-wire drilling along the planned trajectory. Pre and postoperative 3D-CT reconstructions was used to evaluate the screw accuracy according to Gertzbein and Robbins classification. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to examine SPC-guided agreements for CBT screw placement. RESULTS: A total of 48 screws were documented in the study. Clinically acceptable trajectory (grades A and B) was accessed in 100% of 48 screws in the planning screws group, and 93.8% of 48 screws in the inserted screws group (p = 0.242). The incidence of proximal facet joint violation (FJV) in the planning screws group (2.1%) was comparable to the inserted screws group (6.3%) (p = 0.617). The lateral angle and cranial angle of the planned screws (9.2 ± 1.8° and 22.8 ± 5.6°) were similar to inserted screws (9.1 ± 1.7° and 23.0 ± 5.1°, p = 0.662 and p = 0.760). Reliability evaluated by intraclass correlation coefficients and Bland-Altman showed good consistency in cranial angle and excellent results in lateral angle and distance of screw tip. CONCLUSIONS: Compared with preoperative planning screws and the actually inserted screws, the SPC guide could achieve reliable execution for cortical screw placement.


Asunto(s)
Tornillos Pediculares , Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Reproducibilidad de los Resultados , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Cadáver
6.
Synapse ; 75(10): e22219, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34269482

RESUMEN

Chronic constriction injury (CCI) of the sciatic nerve was used to establish neuropathic pain (NP) models in rats. CCI rats were then treated with propofol (Pro) and their paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured. In addition, the expression patterns of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-10 were detected. CCI rats treated with propofol were further injected with antagomiR-140-3p to verify the role of miR-140-3p in propofol's analgesic actions. In addition to confirming the relationship between miR-140-3p and JAG1, the expression patterns of JAG1 itself were detected. Propofol-treated CCI rats were also injected with Ad-JAG1 (adenovirus-packaged JAG1 overexpression vector and Ad-NC) to test the role of JAG1 in propofol's analgesic mechanism of action. Finally, the levels of JAG1 and Notch pathway-related proteins were detected RESULTS: Propofol was found to alleviate NP, including thermal hyperalgesia and mechanical pain threshold. Propofol could also ameliorate neuroinflammation by up-regulating the expression of IL-10 and inhibiting the release of TNF-α and IL-1ß. Mechanically, propofol enhanced the amount of miR-140-3p in CCI rats via the regulation of JAG1. Down-regulation of miR-140-3p, or up-regulation of JAG1, could reduce the protective effect of propofol against NP. Propofol inhibited the activation of Notch signaling via miR-140-3p/JAG1 to realize its analgesic effect CONCLUSION: Our findings indicated that propofol inhibits inflammatory responses and the Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP. These data provide evidence to support a potential clinical therapy for NP.


Asunto(s)
MicroARNs , Neuralgia , Propofol , Animales , Constricción , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Proteína Jagged-1/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Propofol/farmacología , Propofol/uso terapéutico , Ratas , Ratas Sprague-Dawley , Transducción de Señal
7.
J Clin Lab Anal ; 35(2): e23645, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33219721

RESUMEN

BACKGROUND: The prostate cancer (PCa) has been a global problem to men health. Notably, the androgen receptor (AR) is essential for both normal development of prostate and prostate cancer progression. METHODS: The RNA sequencing was used to identify the novel long non-coding RNA (lncRNA) termed PCAL7. The RT-qPCR was performed to quantify PCAL7 expression. Migration and proliferation assays were used to examine the function of PCAL7. Fluorescence in situ hybridization (FISH) was used to determine subcellular localization. RESULTS: By RNA sequencing, the differentially expressed lncRNAs were identified (top 10 upregulated lncRNAs: PCAL7, AC083843.1, CTC-338M12.3, RP11-443B7.1, RP11-1008C21.2, RN7SL329P, RP4-773N10.4, RP11-264B17.2, KB-1507C5.2, and RP11-20B24.6; top 10 downregulated lncRNAs: RP11-77H9.2, RAB11FIP1P1, AP001625.6, CTA-217C2.1, RP11-603J24.7, RP11-315I20.1, AC092839.1, RP4-758J18.10, RP11-259O2.3, and HMGN2P17). PCAL7 was the lncRNA with the highest fold upregulation and significantly correlated with AR signaling during prostate cancer progression. The AR-regulated PCAL7 was abundantly overexpressed in prostate cancer tissues and AR-dependent cell lines. PCAL7 knockdown inhibited cell migration and proliferation. Consistently, the migration and proliferation were promoted by PCAL7 overexpression. PCAL7 depletion via antisense oligonucleotides (ASOs) markedly suppressed AR signaling and tumor growth. Mechanistically, PCAL7 interacted with Huntingtin-interacting protein 1 (HIP1) to stabilize HIP1. Therefore, PCAL7 could advance AR signaling via a novel positive feedback loop. CONCLUSION: Our experiments support an oncogenic role for PCAL7 which promotes prostate cancer progression suggesting PCAL7 may serve as a potential therapeutic target.


Asunto(s)
Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , ARN Largo no Codificante/genética , Receptores Androgénicos/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Citoplasma/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/genética , Transducción de Señal
8.
Andrologia ; 52(11): e13774, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32786090

RESUMEN

We reported our initial experience of robotic-assisted laparoscopic artery-sparing varicocelectomy using indocyanine green (ICG) fluorescence angiography in treatment of varicocele. A total of 45 varicocelectomies in 27 patients were performed. The mean operation time was 49.1 ± 8.5 min for unilateral and 65.6 ± 8.3 min for bilateral repair. 47.2 s after ICG injection, testicular artery (TA) was visualised. After an interval of 31.3 s, fluorescent veins were identified. Of all the 45 spermatic cords, 68.9% had a solitary artery, while 31.1% had 2 arteries. The mean hospital stay was 1.6 ± 0.9 days. Semen concentration and motility were significantly improved 6 months after surgery, no recurrence, hydrocele or testicular atrophy was observed. Our study demonstrated that robotic-assisted laparoscopic artery-sparing varicocelectomy using ICG fluorescence angiography is a safe, effective and promising technique in treatment of varicocele.


Asunto(s)
Laparoscopía , Procedimientos Quirúrgicos Robotizados , Varicocele , Arterias , Angiografía con Fluoresceína , Humanos , Verde de Indocianina , Masculino , Resultado del Tratamiento , Varicocele/diagnóstico por imagen , Varicocele/cirugía
9.
Urol Int ; 102(4): 385-389, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30712042

RESUMEN

BACKGROUND: Ureteral stenting is a technique-demanding procedure performed during robot-assisted laparoscopic ureteral reimplantation (RALUR). Many stenting techniques have been reported; however, none of them could be accepted as an ideal way. OBJECTIVES: The aim of the study was to report our initial results of a modified stenting technique for RALUR. METHODS: Consecutive 4 patients undergoing RALUR were prospectively enrolled into our study. Our ureteral stenting technique included the following steps: catheterize a head-cut Foley catheter at the beginning of the operation, drag out the Foley catheter from the ureterovesical stoma after finishing posterior anatomosis, insert a guide wire through the catheter to the ureter lumen, and place the double-J (DJ) stent over the guide wire with a pusher. RESULTS: All surgeries were successfully performed without severe complications. The mean stenting time was 1.6 min. No submucosa pseudocanal was found during stenting. DJ stent was removed 4 weeks after surgery. During the 3-month follow-up, it was observed that no vesicoureteral reflux or ureter stricture was found. CONCLUSIONS: Our ureteral stenting technique is an effective, simple, and safe procedure in RALUR, and could also be performed in laparoscopic ureteral reimplantation.


Asunto(s)
Laparoscopía/métodos , Reimplantación/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Stents , Uréter/cirugía , Obstrucción Ureteral/cirugía , Anastomosis Quirúrgica , Constricción Patológica/cirugía , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Neoplasias Ureterales/cirugía , Cateterismo Urinario , Reflujo Vesicoureteral/cirugía
10.
Kidney Blood Press Res ; 43(4): 1084-1103, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29991025

RESUMEN

BACKGROUND/AIMS: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-κB signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. METHODS: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1ß and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. RESULTS: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-α, IL-1ß and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-κB, IL-6, TNF-α and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-κB signaling pathway. CONCLUSION: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-κB signaling pathway in rats with renal I/R injury.


Asunto(s)
Apoptosis , Citocinas/metabolismo , Células Epiteliales/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Animales , Proliferación Celular , Silenciador del Gen , Inflamación , Riñón/lesiones , Túbulos Renales/patología , Lentivirus , FN-kappa B/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/farmacología , Ratas , Daño por Reperfusión , Transducción de Señal , Receptor Toll-Like 4/metabolismo
11.
Rev Invest Clin ; 70(4): 169-176, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30067728

RESUMEN

Background: Accurate assessing donor renal function is crucial to the success of living kidney transplants. We studied the roles of donor kidney glomerular filtration rate (GFR) and donor/recipient body surface area (BSA) ratio in kidney selection for living transplantation from family members. Methods: We included 204 recipients who were subjected to living kidney transplantation from family members in our hospital from February 2011 to February 2015 and followed up for over 2 years. Recipients were divided into six groups according to donor GFR and donor/recipient BSA ratio. The effects of donor GFR or donor/recipient BSA ratio on the recovery of renal graft functions were evaluated. Results: The post-operative serum creatinine (SCr) reduction rate, steady-state SCr level, and estimated GFR (eGFR) of the group with donor GFR ≥ 40 ml/min were slightly higher to those of the group with donor GFR < 40 ml/min (p > 0.05). The renal function recovery of the group with donor/recipient BSA ratio ≤ 0.8 was significantly lower than that of the group with donor/recipient BSA ratio ≥ 1.2 (p < 0.05). The post-operative SCr reduction rate, steady-state SCr level, and eGFR of the group with GFR < 40 ml/min and donor/recipient BSA ratio ≤ 0.8 were all significantly lower than those of the other five groups (P < 0.05). Such values of the two groups with donor/recipient BSA ratio >1.2 were significantly higher than those of the other four groups (p < 0.05). Conclusions: The selection of donor kidneys from relatives for living kidney transplantation should also consider donor/recipient BSA ratio in addition to donor GFR.


Asunto(s)
Tasa de Filtración Glomerular/fisiología , Trasplante de Riñón/métodos , Donadores Vivos , Receptores de Trasplantes , Adulto , Superficie Corporal , Creatinina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
12.
Clin Lab ; 63(2): 313-320, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-28182363

RESUMEN

BACKGROUND: Lung cancer is one of the most common malignancies across the world. Long noncoding RNAs (lncRNAs) play an important role in the pathology. This study was to compare the lncRNA and mRNA of lung cancer. The aim of this study was to compare the lncRNA and mRNA expression profiles, their related biological functions, and pathways in lung cancer. METHODS: Human lung cancer mRNA expression datasets were searched and downloaded from NCBI-GEO. LncRNA expression profiles in lung cancer were detected by the Agilent Human LncRNA Microarray V3.0. Differential expression analysis was conducted between cases and controls in mRNA and lncRNA. The starBase web server v2.0 was used to decipher lncRNA-protein interactions. DAVID Bioinformatics Resources 6.7 was used to perform GO Biological Processes and KEGG pathway enrichment analysis of these dysregulated mRNA and lncRNA target genes. RESULTS: The study showed that differentially expressed lncRNA target genes included almost all of the differential expression genes from mRNA. Furthermore, these dysregulated lncRNAs reflected more comprehensive impairment in functional enrichment than dysregulated mRNAs. In addition, five top downregulated lncRNAs had more remarkable fold changes than top downregulated mRNAs, especially FENDRR. CONCLUSIONS: Amount of lncRNAs and mRNAs were differentially expressed in lung cancer. The degrees of difference in lncRNAs were more than mRNAs. It may provide valuable help for an effective strategy in diagnosis and prevention.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Pulmonares/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Transcriptoma , Biología Computacional , Bases de Datos Genéticas , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo
13.
Tumour Biol ; 37(6): 8293-304, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26729194

RESUMEN

Krüppel-like factor 4 (KLF4) is a transcription factor involved in both tumor suppression and oncogenesis as a transcriptional activator or repressor in a context-dependent manner. KLF4 acts as a regulator of p53 depending on p21 status in breast cancer. However, the mechanisms underlying the distinct role of KLF4 remain poorly understood. Here, we revealed that p21 depletion converted KLF4 from a cell cycle inhibitor to a promoter of bladder cancer cell proliferation. Additionally, KLF4 was acetylated in a p21-dependent manner to inhibit bladder cancer cell growth as a tumor suppressor. However, deacetylated KLF4 functioned as an oncogene promoting bladder cancer cell proliferation. Mechanistically, p21 and CK2 interaction, but not CK2 alone, enhanced HDAC2 phosphorylation and restricted KLF4 deacetylation and subsequent tumor promotion. Furthermore, we observed that KLF4 was acetylated by CBP/p300 and that overexpression of CBP resulted in KLF4 acetylation and tumor suppression even in p21-depleted bladder cancer cells. Moreover, we discovered that Notch-1 knockdown-induced KLF4 is acetylated form of KLF4, which may mediate Notch-1 function in bladder cancer cell proliferation. Our data demonstrate that KLF4 acts as a tumor suppressor or oncogene to activate or repress target gene transcription depending on its acetylation status, which is regulated by p21 and CK2 interaction-mediated HDAC2 phosphorylation. Targeting KLF4 at the post-transcriptional levels may provide novel insight for bladder cancer therapy.


Asunto(s)
Quinasa de la Caseína II/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Histona Desacetilasa 2/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Acetilación , Western Blotting , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , Inmunoprecipitación , Factor 4 Similar a Kruppel , Fosforilación , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo
14.
Lancet ; 381(9882): 2024-32, 2013 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-23726161

RESUMEN

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.


Asunto(s)
Enterovirus Humano A/inmunología , Infecciones por Enterovirus/prevención & control , Vacunas Virales/inmunología , Adyuvantes Inmunológicos/efectos adversos , Compuestos de Alumbre , Anticuerpos Antivirales/sangre , Preescolar , Método Doble Ciego , Infecciones por Enterovirus/inmunología , Femenino , Humanos , Inmunidad Activa/fisiología , Lactante , Estimación de Kaplan-Meier , Masculino , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/efectos adversos
15.
Tumour Biol ; 35(7): 6405-14, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24671824

RESUMEN

Interferon gamma (IFN-γ) is a potent proinflammatory cytokine which plays a pivotal role in the antiviral, antiproliferative, and antitumor activities. A T-to-A transition at the position +874 of human IFN-γ gene (IFNG) has been reported to influence the secretion of IFN-γ and affect cancer susceptibility. However, results from published studies on the association between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even controversial. In order to derive a more precise estimation of the association, a meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI). Overall, no significant association was detected in allelic model (A allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs. TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03, 95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87-1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12). Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg equilibrium status failed to demonstrate any significant relationship except in African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47-0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A polymorphism may not contribute to cancer susceptibility, and further well-designed studies with large sample size are warranted to validate our conclusion.


Asunto(s)
Predisposición Genética a la Enfermedad , Interferón gamma/genética , Neoplasias/genética , Alelos , Estudios de Asociación Genética , Humanos , Factores de Riesgo
16.
Clin Exp Obstet Gynecol ; 41(6): 677-80, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25566593

RESUMEN

BACKGROUND: The objective of this study was to evaluate the efficacy and side-effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of moderate or severe dysmenorrhea associated with adenomyosis and the influence on ovarian function. STUDY DESIGN: The LNG-IUS was inserted into 60 women who had moderate or severe dysmenorrhea associated with adenomyosis diagnosed by transvaginal sonography. A visual analogue scale (VAS) of dysmenorrhea, uterine volume and serum-levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), etstradiol (E2), and prolactin (PRL) were used to assess the efficacy of the treatment at base- line and at six and 12 months after the LNG-IUS. Serum-levels ofFSH, LH, E2, and PRL were tested in pre-and post-insertion at six and at 12 months, respectively. Side-effects were recorded at every follow-up visit. RESULTS: After six and 12 months of LNG-IUS insertion, dysmenorrhea was obviously alleviated, and the dysmenorrhea scores decreased to 2.6 from 0.6 (p < 0.05). The volume of uterus reduced six months after insertion and later, but without significant change (p <0.05). After treatment of serum, in terms ofFSH, LH, and E2 lev- els, compared with pre-insertion, there was no statistically significant difference (p > 0.01). However, the level of PRL markedly de- clined at six and 12 months after LNG-IUS. CONCLUSION: The LNG-IUS appears to be an effective method in alleviating dysmenorrhea associated with adenomyosis with little effect on ovarian function. It may be helpful to decrease the level of PRL in these patients.


Asunto(s)
Adenomiosis/complicaciones , Dismenorrea/tratamiento farmacológico , Dispositivos Intrauterinos Medicados , Levonorgestrel/administración & dosificación , Adulto , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Persona de Mediana Edad , Dimensión del Dolor
17.
Explore (NY) ; 20(2): 261-263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37673761

RESUMEN

BACKGROUND: Warts result from an infection with the human papilloma virus (HPV). Plantar warts, also known as Verruca plantaris, can be notably painful for the patient and possess contagious qualities, thus necessitating assertive treatment. Despite several available approaches for addressing plantar warts, efficacy remains elusive. CASE PRESENTATION: One 22-year-old firefighter suffered from numerous plantar warts. After 26 days of traditional Chinese medicine soaking, the rashes completely disappeared. The treatment was without complications or discomfort, and a three-month follow-up showed no recurrence. CONCLUSION: Our case investigation highlighted the efficacy of herbal soaking as a safe, painless, and non-invasive therapeutic option, positioning it as a potential avenue for managing multiple plantar warts.


Asunto(s)
Enfermedades del Pie , Verrugas , Humanos , Anciano de 80 o más Años , Medicina Tradicional China , Verrugas/tratamiento farmacológico , Enfermedades del Pie/terapia , Papillomaviridae , Resultado del Tratamiento
18.
Eur Urol Open Sci ; 64: 2-8, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38694878

RESUMEN

Background and objective: Robot-assisted radical prostatectomy (RARP) is widely used because of the many advantages of a robotic approach. The da Vinci Si robot is one of the most commonly used surgical robot systems, but it may be associated with higher costs owing to the use of consumable surgical supplies. Our aim was to conduct a preliminary investigation of the capability of the MP1000 system for RARP. Methods: In this prospective, multicentre, single-blinded study, we randomly assigned 42 patients scheduled to undergo RARP between April and September 2021 to a da Vinci Si group (control) or an MP1000 group (intervention). Patients underwent RARP performed using the assigned robotic system and were followed up at 3-mo intervals. The primary outcome was the rate of conversion to open/laparoscopic surgery. Secondary outcomes were installation and operation times, intraoperative blood loss, postoperative surgical margin status, hospital stay, incontinence, complications, safety indicators, and surgeon ergonomics. Key findings and limitations: All procedures were successfully completed without conversion to open/laparascopic surgery or major complications. Secondary outcomes, including oncological and ergonomic indicators, did not differ significantly between the groups over the study period. One patient in the control group experienced dysuria (Clavien-Dindo grade 3). No patients had incontinence at 3 mo. A limitation of the study is the small sample size. Conclusions and clinical implications: RARP with the MP1000 system is feasible, safe, and effective in the management of localised prostate cancer. Patient summary: We assessed the effectiveness and safety of the new MP1000 robot system for robot-assisted removal of the prostate in comparison to the da Vinci Si robot. We found no difference in effectiveness or safety among 42 patients with prostate cancer who were assigned randomly to one of the two systems. We conclude that the MP1000 is a suitable robot for this surgery.

19.
Int J Surg ; 110(5): 2803-2809, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38349210

RESUMEN

PURPOSE: This study aimed to compare the safety and effectiveness of the MP1000 surgical system with the da Vinci Si robot system in robot-assisted partial nephrectomy (RAPN) through a prospective, single-blinded, randomized controlled trial. MATERIALS AND METHODS: A total of 62 patients who were scheduled to undergo RAPN were randomly assigned to either the da Vinci Si robot or MP1000 group. A noninferiority test was conducted with a noninferior intermediate value of 10%. The study compared installation and operation times, estimated blood loss, warm ischemia time, postoperative surgical margin, rate of conversion to open surgery, eGFR level, complications, and other safety indicators between the two groups. RESULTS: All procedures were successfully completed without the need for conversion to open or laparoscopic surgery, and no major complications were observed during the process. The test of noninferiority was achieved. There were no significant differences in median installation time, operation time, complication rate at 3 months, rate of positive surgical margin, and eGFR level at 3 months between the groups. Additionally, no evidence of recurrence was found on imaging in both groups. No difference in National Aeronautics and Space Administration task load index results for ergonomic considerations. A limitation of this study was its small sample size. CONCLUSIONS: The MP1000 system is a suitable platform for RAPN with safety and effectiveness compared with da Vinci Si system.


Asunto(s)
Neoplasias Renales , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Nefrectomía/métodos , Nefrectomía/instrumentación , Nefrectomía/efectos adversos , Procedimientos Quirúrgicos Robotizados/instrumentación , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Neoplasias Renales/cirugía , Método Simple Ciego , Tempo Operativo , Adulto , Resultado del Tratamiento
20.
World J Gastroenterol ; 30(1): 91-107, 2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-38293320

RESUMEN

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Selenio , Animales , Ratones , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Selenito de Sodio/farmacología , Ratones Endogámicos C57BL , Citotoxinas , Infecciones por Helicobacter/metabolismo
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