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1.
Gen Physiol Biophys ; 40(3): 207-219, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34100377

RESUMEN

Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.


Asunto(s)
Artritis Reumatoide , MicroARNs , Sinoviocitos , Apoptosis , Artritis Reumatoide/genética , Proliferación Celular , Células Cultivadas , Fibroblastos , Humanos , Péptidos y Proteínas de Señalización Intracelular , MicroARNs/genética , Receptor Toll-Like 4/genética
2.
Am J Physiol Cell Physiol ; 313(4): C448-C459, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28747335

RESUMEN

Both zinc (Zn2+) and reactive oxygen species (ROS) have been shown to accumulate during hypoxic-ischemic stress and play important roles in pathological processes. To understand the cross talk between the two of them, here we studied Zn2+ and ROS accumulation by employing fluorescent probes in HeLa cells to further the understanding of the cause and effect relationship of these two important cellular signaling systems during chemical-ischemia, stimulated by oxygen and glucose deprivation (OGD). We observed two Zn2+ rises that were divided into four phases in the course of 30 min of OGD. The first Zn2+ rise was a transient, which was followed by a latent phase during which Zn2+ levels recovered; however, levels remained above a basal level in most cells. The final phase was the second Zn2+ rise, which reached a sustained plateau called Zn2+ overload. Zn2+ rises were not observed when Zn2+ was removed by TPEN (a Zn2+ chelator) or thapsigargin (depleting Zn2+ from intracellular stores) treatment, indicating that Zn2+ was from intracellular storage. Damaging mitochondria with FCCP significantly reduced the second Zn2+ rise, indicating that the mitochondrial Zn2+ accumulation contributes to Zn2+ overload. We also detected two OGD-induced ROS rises. Two Zn2+ rises preceded two ROS rises. Removal of Zn2+ reduced or delayed OGD- and FCCP-induced ROS generation, indicating that Zn2+ contributes to mitochondrial ROS generation. There was a Zn2+-induced increase in the functional component of NADPH oxidase, p47phox, thus suggesting that NADPH oxidase may mediate Zn2+-induced ROS accumulation. We suggest a new mechanism of cross talk between Zn2+ and mitochondrial ROS through positive feedback processes that eventually causes excessive free Zn2+ and ROS accumulations during the course of ischemic stress.


Asunto(s)
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Glucosa/deficiencia , Mitocondrias/metabolismo , Estrés Oxidativo , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Zinc/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Isquemia Encefálica/patología , Hipoxia de la Célula , Quelantes/farmacología , Retroalimentación Fisiológica , Células HeLa , Humanos , Técnicas In Vitro , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ionóforos de Protónes/farmacología , Ratas Sprague-Dawley , Transducción de Señal , Factores de Tiempo
3.
Nutr J ; 16(1): 11, 2017 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-28183318

RESUMEN

BACKGROUND & AIMS: Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. METHODS: Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. RESULTS: One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P < 0.05). The median postoperative length of stay in the multimodal EON group was 8 days (6, 12) versus 10 days (7, 18) in the conventional care group (P < 0.001). The total cost of treatment and nutritional support were also less in the multi-modal early oral nutrition group (P < 0.001). The effectiveness was 84.9 and 79.9% in the multimodal EON and conventional care group, respectively (P = 0.475). However, the cost-effectiveness ratio was USD 537.6 (506.1, 589.3) and USD 637.8 (593.9, 710.3), respectively (P < 0.001). CONCLUSION: The multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal surgery. TRIAL REGISTRATION: Registration number: ChiCTR-TRC-14004395 . Registered 15 March 2014.


Asunto(s)
Abdomen/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Apoyo Nutricional , Cuidados Posoperatorios/métodos , Anciano , Colectomía , Análisis Costo-Beneficio , Defecación/fisiología , Determinación de Punto Final , Femenino , Gastrectomía , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estado Nutricional , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Tamaño de la Muestra , Método Simple Ciego
4.
Nutr J ; 15(1): 78, 2016 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-27543156

RESUMEN

OBJECTIVE: To investigate the impact of nutritional support on clinical outcomes in patients at nutritional risk who receive nutritional support that meets guideline standards and those who do not. METHODS: This prospective cohort study enrolled hospitalized patients from the Second Affiliated Hospital of Kunming Medical University from February 2010 to June 2012. The research protocols were approved by the university's ethics committee, and the patients signed informed consent forms. The clinical data were collected based on nutritional risk screening, administration of enteral and parenteral nutrition, surgical information, complications, and length of hospital stay. RESULTS: During the study period, 525 patients at nutritional risk were enrolled in the cohorts. Among patients who received nutritional support that met the guideline standards (Cohort 1), the incidence of infectious complications was lower than that in patients who did not meet guideline standards (Cohort 2) (17.1 % vs. 26.9 %, P = 0.01). Subgroup analysis showed that individuals who received a combination of parenteral nutrition (PN) and enteral nutrition (EN) for 7 or more days had a significantly lower incidence of infectious complications (P = 0.001) than those who received only PN for 7 or more days or those who received nutritional support for less than 7 days or at less than 10 kcal/kg/d. Binary logistic regression analysis showed that, after adjusting for confounding factors, nutritional support that met guideline standards for patients with nutritional risk was a protective factor for complications (OR: 0.870, P < 0.002). CONCLUSIONS: In patients at nutritional risk after abdominal surgery, nutritional support that meets recommended nutrient guidelines (especially regimens involving PN + EN ≥ 7 days) might decrease the incidence of infectious complications and is worth recommending; however, well-designed trials are needed to confirm our findings. Nutritional support that does not meet the guideline standards is considered clinically undesirable.


Asunto(s)
Política Nutricional , Apoyo Nutricional , Cuidados Posoperatorios , Abdomen/cirugía , Anciano , China/epidemiología , Estudios de Cohortes , Nutrición Enteral/métodos , Femenino , Humanos , Infecciones/epidemiología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Apoyo Nutricional/normas , Nutrición Parenteral/métodos , Complicaciones Posoperatorias/epidemiología , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento
5.
J Cancer Res Ther ; 20(2): 726-735, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38687946

RESUMEN

BACKGROUND: As an antioncogene gene, phosphataseandtensinhomolog (PTEN) is closely related to tumorigenesis. However, after mutation, PTEN will lose its function and no longer exert a tumor suppression effect. Through this research, we explored the impact of PTEN mutation on hepatic carcinoma (HCC) and the mechanism of PTEN for regulating HCC. METHODS: First, bioinformatics was used to analyze the prognosis of PTEN in HCC. PTEN-related genes were then further analyzed by the LinkedOmics database, and GO and KEGG functional enrichment analysis were performed. Next, databases were utilized to predict the mutation and mutation frequency of PTEN. Eventually, CRISPR-Cas12a was applied to detect the R130Q mutation on PTEN in clinical samples of HCC. Finally, the fact that miR-92a-3p targets PTEN was identified by dual luciferase reporter gene assays, RT-qPCR, western blot, and rescue experiments. RESULTS: Bioinformatics analysis indicated the high mutation frequency of R130Q/G/L* site on the PTEN gene. Through CRISPR-Cas12a, R130Q mutation was detected on PTEN in 26 out of 40 clinical samples of HCC. CONCLUSIONS: On the one hand, our study revealed that CRISPR-Cas12a might play an important role in the screening and prognosis of HCC as a new clinical method to detect PTEN mutation.


Asunto(s)
Carcinoma Hepatocelular , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , MicroARNs , Mutación , Fosfohidrolasa PTEN , Fosfohidrolasa PTEN/genética , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Pronóstico , MicroARNs/genética , Biología Computacional/métodos , Sistemas CRISPR-Cas/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular/genética
6.
Front Microbiol ; 15: 1355725, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38746746

RESUMEN

Background: Increasing evidence indicates that gut microbiota dysbiosis is related to synovitis and tenosynovitis. Nonetheless, whether these associations are causal is currently unknown. Objectives: A two-sample Mendelian randomization (MR) study was performed to reveal the causality of gut microbiota with synovitis and tenosynovitis. Methods: The summary statistical data from a large-scale genome-wide association study (GWAS) were applied as the basis for a two-sample MR analysis. The causal effect was estimated using inverse variance weighted (IVW), weighted median, simple mode, MR-Egger, and weighted mode methods, of which IVW was the important method. Meanwhile, the pleiotropy and heterogeneity were detected and measured using MR-Egger regression, Cochran's Q statistics, funnel plots, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Results: The IVW technique demonstrated that genetically predicted five genera, namely Gordonibacter [odds ratio (OR) = 0.999, 95% confidence interval (CI): (0.9977, 0.9998), p = 0.019], Paraprevotella [OR = 0.999, 95% CI: (0.9971, 0.9999), p = 0.036], Lachnoclostridium [OR = 0.998, 95% CI: (0.9954, 0.9999), p = 0.041], RuminococcaceaeUCG003 [OR = 0.997, 95% CI: (0.9955, 0.9994), p = 0.011], and FamilyXIIIAD3011group [OR = 0.997, 95% CI: (0.9954, 0.9992), p = 0.006] were negatively correlated with the risk of synovitis and tenosynovitis, while two other genera, namely Ruminococcustorquesgroup [OR = 1.003, 95% CI: (1.0004, 1.0049), p = 0.019] and Parabacteroides [OR = 1.003, 95% CI: (1.0002, 1.0052), p = 0.035] were positively associated with synovitis and tenosynovitis risk. In addition, the data of sensitivity analyses demonstrated that there were no outliers, horizontal pleiotropy, or heterogeneity in the causal relationship of the above-mentioned gut microbiota on synovitis and tenosynovitis (p > 0.05). Conclusion: The results of the study suggested that the gut microbiota was causally involved in synovitis and tenosynovitis and identified specific bacterial taxa that affect synovitis and tenosynovitis, which provide new insights into the pathogenesis underlying the development of synovitis and tenosynovitis mediated by gut microbiota.

7.
Photodiagnosis Photodyn Ther ; 49: 104319, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39181490

RESUMEN

Photodynamic therapy (PDT) is a promising and innovative approach for treating tumors. The synergistic effect of PDT and chemotherapy can enhance the anti-tumor efficacy by leveraging their complementing benefits. In this study, we created lipid vesicles to deliver a photosensitizer (chlorin e6, Ce6) and Regorafenib into tumors for the purpose of examining the effectiveness and mechanism of Lipo-Ce6@Rego-PDT (LCR-P) on Hepatocellular carcinoma (HCC) both in vitro and in vivo. We found that the cytotoxicity on HCC caused by LCR-P was significantly stronger than that caused by Lipo-Ce6-PDT (LC-P). Cellular ROS production in the LCR-P group was approximately higher than that in the LC-P group, and Regorafenib significantly inhibited the phosphorylation of JNK, ERK, and P38 of Lipo-Ce6-PDT group in vitro and in vivo. Furthermore, Regorafenib significantly downregulated the expression of Bcl-2 and upregulated the expression of Bax and cleaved caspase-3 of LC-P group in vitro and in vivo. Compared with LC-P, LCR-P significantly increased cell apoptosis rate. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. These results indicate that the combination of Regorafenib and Lipo-Ce6 can significantly enhance the anti-tumor efficiency of PDT for HCC and exhibits good biosafety.

8.
Sci Total Environ ; 952: 175860, 2024 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-39214351

RESUMEN

Eutrophication triggered by internal phosphorus (P) poses a substantial threat to the biodiversity of organisms in freshwater ecosystems. However, little is known about the linkages between P resource partitioning and microbial succession, especially in karst sediments. Here, we studied the diversity patterns and assembly processes of bacterial and archaeal communities in sediment cores from two historically hyper-eutrophicated karst lakes, Hongfeng Lake and Aha Lake, and investigated the relative contribution of P fractions to them. Our null and neutral models consistently indicated that bacterial and archaeal community assembly was judged to be deterministic rather than stochastic. We found a monotonically decreasing pattern for bacterial Shannon diversity toward deep sediments in Aha Lake, but U- or hump-shaped patterns for archaea in Hongfeng and Aha Lakes. Intriguingly, the community dissimilarity Bray-Curtis of bacteria and archaea consistently increased with increasing depth distance, with slopes of 0.0080 and 0.0069 in Hongfeng Lake and 0.0078 and 0.0087 in Aha Lake, respectively. Such cross-taxon congruence was well-supported by equivalent ecological processes (i.e., environmental selection). For bacteria and archaea, Shannon diversity was primarily affected by the total P (TP) fractions such as the loosely adsorbed TP or calcium-bound TP and sediment TP. Their community composition was significantly (P < 0.05) affected by calcium-bound inorganic P (Pi), loosely adsorbed Pi and reductant-soluble Pi. Although sediment properties were important, bacterial and archaeal diversity or community composition were well-explained by the Pi fractions, with high direct or indirect effects. In particular, Pi fractions exhibited stronger effects on bacterial and archaeal characteristics than organic P fractions. Taken together, our study provides novel insights into the ecological importance of P resource partitioning to microbial succession, which has crucial implications for disentangling the biogeochemical processes of P cycling in aquatic ecosystems.


Asunto(s)
Archaea , Bacterias , Biodiversidad , Lagos , Microbiota , Fósforo , Fósforo/análisis , Lagos/microbiología , Lagos/química , Bacterias/clasificación , Sedimentos Geológicos/microbiología , Sedimentos Geológicos/química , Eutrofización , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , China
9.
Fitoterapia ; 176: 106053, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38838828

RESUMEN

Biotransformation of ursane-type triterpenoid ilexgenin A by endophytic fungi Lasiodiplodia sp. MQD-4 and Pestalotiopsis sp. ZZ-1, isolated from Ilex pubescences and Callicarpa kwangtungensis respectively, was investigated for the first time. Six previously undescribed metabolites (1-6) with 23-norursane triterpenoids skeleton were isolated and their structures were unambiguously established by the analysis of spectroscopic data and single-crystal X-ray crystallographic experiments. Decarboxylation, oxidation, and hydroxylation reactions were observed on the triterpenoid skeleton. Especially, the decarboxylation of C-23 provided definite evidence to understand the biogenetic process of 23-norursane triterpenoids. Moreover, the qualitative analysis of the extract of I. pubescences showed metabolites 1, 3, 4, and 6 could be detected in the originated plant, indicating biotransformation by endophytic fungi is a practical strategy for the isolation of novel natural products. Finally, all isolates were evaluated for the protective activities against H2O2-induced HUVECs dysfunction in vitro. Compound 5 could improve the viability of endothelial cells and decrease the level of intracellular ROS.


Asunto(s)
Biotransformación , Endófitos , Células Endoteliales de la Vena Umbilical Humana , Ilex , Triterpenos , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Triterpenos/metabolismo , Endófitos/química , Endófitos/metabolismo , Estructura Molecular , Humanos , Ilex/microbiología , Ascomicetos/química , Ascomicetos/metabolismo , China
10.
J Huazhong Univ Sci Technolog Med Sci ; 33(6): 810-816, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24337840

RESUMEN

Autophagy is a conserved and programmed catabolic process that degrades damaged proteins and organelles. But the underlying mechanism and functions of autophagy in the ischemia-reperfusion (IR)-induced injury are unknown. In this study, we employed simulated IR of N2a cells as an in vitro model of IR injury to the neurons and monitored autophagic processes. It was found that the levels of Beclin-1 (a key molecule of autophay complex, Beclin-1/class III PI3K) and LC-3II (an autophagy marker) were remarkably increased with time during the process of ischemia and the process of reperfusion after 90 min of ischemia, while the protein kinases p70S6K and mTOR which are involved in autophagy regulation showed delayed inactivation after reperfusion. Administration of 3-methyladenine (3MA), an inhibitor of class III PI3K, abolished autophagy during reperfusion, while employment of rapamycin, an inhibitor of mTORC1 (normally inducing autophagy), surprisingly weakened the induction of autophagy during reperfusion. Analyses of mitochondria function by relative cell viability demonstrated that autophagy inhibition by 3-MA attenuated the decline of mitochondria function during reperfusion. Our data demonstrated that there were two distinct dynamic patterns of autophagy during IR-induced N2a injury, Beclin-1/class III PI3K complex-dependent and mTORC1-dependent. Inhibition of over-autophagy improved cell survival. These suggest that targeting autophagy therapy will be a novel strategy to control IR-induced neuronal damage.


Asunto(s)
Autofagia , Neuronas/metabolismo , Daño por Reperfusión/metabolismo , Adenina/análogos & derivados , Adenina/farmacología , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Beclina-1 , Línea Celular Tumoral , Supervivencia Celular , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Mitocondrias/metabolismo , Complejos Multiproteicos/antagonistas & inhibidores , Complejos Multiproteicos/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo
11.
Front Microbiol ; 14: 1279751, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37886062

RESUMEN

Both community variation and phosphorus (P) fractions have been extensively studied in aquatic ecosystems, but how P fractions affect the mechanism underlying microbial beta diversity remains elusive, especially in sediment cores. Here, we obtained two sediment cores to examine bacterial and archaeal beta diversity from mesotrophic lakes Hongfeng Lake and Aha Lake, having historically experienced severe eutrophication. Utilizing the Baselga's framework, we partitioned bacterial and archaeal total beta diversity into two components: species turnover and nestedness, and then examined their sediment-depth patterns and the effects of P fractions on them. We found that total beta diversity, species turnover or nestedness consistently increased with deeper sediment layers regarding bacteria and archaea. Notably, there were parallel patterns between bacteria and archaea for total beta diversity and species turnover, which is largely underlain by equivalent processes such as environmental selection. For both microbial taxa, total beta diversity and species turnover were primarily constrained by metal oxide-bound inorganic P (NaOH-Pi) and sediment total phosphorus (STP) in Hongfeng Lake, while largely affected by reductant-soluble total P or calcium-bound inorganic P in Aha Lake. Moreover, NaOH-Pi and STP could influence bacterial total beta diversity by driving species nestedness in Hongfeng Lake. The joint effects of organic P (Po), inorganic P (Pi) and total P fractions indicated that P fractions are important to bacterial and archaeal beta diversity. Compared to Po fractions, Pi fractions had greater pure effects on bacterial beta diversity. Intriguingly, for total beta diversity and species turnover, archaea rather than bacteria are well-explained by Po fractions in both lakes, implying that the archaeal community may be involved in Po mineralization. Overall, our study reveals the importance of P fractions to the mechanism underlying bacterial and archaeal beta diversity in sediments, and provides theoretical underpinnings for controlling P sources in biodiversity conservation.

12.
Heliyon ; 9(12): e23082, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38144295

RESUMEN

Background: The haungqing (Scutellariae Radix) and baishao (Paeoniae Radix Alba) herb pair (HBHP) is a common prescribed herbal formula or is added to other traditional Chinese medicine (TCM) prescriptions to treat ulcerative colitis (UC). However, the underlying mechanism is unclear. Purpose: Elucidate the efficacy and potential mechanism of HBHP against UC. Methods: First, The UC model of mice induced by dextran sulfate sodium (DSS) was established. The mice were randomly divided into Control group, DSS group, SASP group (390 mg/kg), and HPHP group (1.95 g/kg), with 8 mice per group. Drugs were administrated via oral gavage for 7 days. Then, Disease activity index (DAI), length of the colon, histopathology, and changes in inflammatory cytokines in colonic tissues were analyzed to assess the effect of HBHP on UC. Besides, Network pharmacology was applied to identify the active compounds, core targets of HBHP in the treatment of UC, and the corresponding signaling pathways to explore the underlying mechanisms. Finally, Western blot (WB), immunohistochemistry (IHC) and molecular docking were performed to validate the results. Results: HBHP significantly reduced DAI score and decreased colon length shortening in DSS-induced UC mice. The administration of HBHP was able to effectively alleviated mucosal ulceration and epithelial destruction. In addition, HBHP treatment obviously - reduced the expressions of TNF-α, IL-6, and IL-1ß in colon tissues (p < 0.05 or p < 0.01). 35 bioactive compounds and 290 HBHP targets related to UC were obtained. Among them 3 key active compounds (baicalein, panicolin, and norwogonin) with higher degree values in the drug-compound-target network and 21 hub genes (STAT3, JAK2, SRC, AKT1, PIK3CA, and VEGFA, etc.) were identified. KEGG enrichment analysis suggested that HBHP's mechanisms mainly involve the JAK-STAT pathway. Abnormal activation of JAK/STAT signaling is believed to be involved in the pathogeneses of UC. Notably, WB and IHC showed that HBHP significantly down-regulated the protein expression levels of p-JAK2 (p < 0.05) and p-STAT3 (p < 0.05 or p < 0.01). JAK2 and STAT3 might be core targets for the action of HBHP; this possibility was also supported by molecular docking. Conclusions: HBHP could alleviate DSS-induced UC, reduce tissue inflammation, and its mechanism might primarily be achieved by inhibiting JAK2/STAT3 signaling pathway. Meanwhile, our work revealed that network pharmacology combined with experimental verification is a cogent means of studying the mechanism of TCM.

13.
Exp Ther Med ; 22(5): 1227, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34539823

RESUMEN

Rheumatoid arthritis (RA) is a serious chronic inflammatory disease and synovial fibroblasts (SFs) serve a vital role in the pathogenesis and progression of RA. Current studies have demonstrated that dysregulation of microRNAs is involved in RA etiopathogenesis. The present study aimed to investigate the role of microRNA (miR)-27a-3p in RASFs, as well as its molecular mechanism. RASFs were isolated from synovial tissues from patients with RA. Expression of miR-27a-3p and toll-like receptor 5 (TLR5) was detected using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation, apoptosis and inflammatory response were measured with MTT assay, flow cytometry and ELISA kits, respectively. The target binding between miR-27a-3p and TLR5 was predicted on DIANA TOOLS software, and confirmed by dual-luciferase reporter assay and Biotin-coupled miRNA pull-down assay. Expression of miR-27a-3p was downregulated and TLR5 was upregulated in synovial tissues and RASFs isolated from patients with RA. Functionally, upregulating miR-27a-3p may promote the apoptosis rate of RASFs and suppress cell proliferation and secretions of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α. TLR5 was validated as a downstream target for miR-27a-3p in RASFs, and its expression was negatively regulated by miR-27a-3p. Silencing TLR5 in RASFs may exert similar effects to miR-27a-3p-overexpression; whereas, restoring TLR5 counteracted the suppression of miR-27a-3p-overexpression on RASF proliferation and inflammation, as well as the promotion on apoptosis. miR-27a-3p upregulation may suppress RA progression by inhibiting RASFs proliferation and inflammation through targeting TLR5.

14.
Exp Ther Med ; 21(6): 559, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33850531

RESUMEN

Long non-coding RNA (lncRNA) ADAM metallopeptidase with thrombospondin type 1 motif 9 antisense RNA 2 (ADAMTS9-AS2) is involved in various types of cancer, such as ovarian cancer, lung cancer and clear cell renal cell carcinoma. However, the roles of ADAMTS9-AS2 in liver cancer are not completely understood. The present study aimed to determine the functional role of ADAMTS9-AS2 in human liver cancer and investigate the potential underlying molecular mechanisms. The expression levels of ADAMTS9-AS2 and ADAMTS9 were determined following ADAMTS9-AS2 overexpression and knockdown. The results indicated that ADAMTS9-AS2 overexpression and knockdown increased and decreased ADAMTS9 mRNA and protein expression levels, respectively, indicating that alterations in ADAMTS9 expression corresponded with ADAMTS9-AS2 expression. Subsequently, the effects of ADAMTS9-AS2 on liver cancer cell proliferation, migration and invasion were analyzed by performing Cell Counting Kit-8, wound healing and Transwell assays, respectively. The results demonstrated that ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion. Finally, the effect of ADAMTS9 on PI3K/AKT/mTOR signaling pathway-associated proteins [AKT, phosphorylated-AKT, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit ß (PIK3CB), mTOR and phosphorylated-mTOR], several key autophagy-related proteins [light chain 3-I/II (LC3-I/II), beclin 1 (BECN1) and sequestosome 1 (SQSTM1)] and apoptosis-related proteins (Bax and Bcl-2) was detected via western blotting. The results suggested that ADAMTS9-AS2 downregulated the phosphorylation of AKT and mTOR, the protein expression level of PIK3CB, as well as the expression levels of autophagy protein SQSTM1 and antiapoptotic protein Bcl-2. By contrast, ADAMTS9-AS2 upregulated the expression levels of autophagy proteins LC3-II and BECN1, and the proapoptotic protein Bax. Collectively, ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion via inhibiting the PI3K/AKT/mTOR signaling pathway. The present study provided a novel insight into the role of ADAMTS9-AS2 in liver cancer.

15.
Hepatol Int ; 14(4): 437-453, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32638296

RESUMEN

Three-dimensional (3D) visualization involves feature extraction and 3D reconstruction of CT images using a computer processing technology. It is a tool for displaying, describing, and interpreting 3D anatomy and morphological features of organs, thus providing intuitive, stereoscopic, and accurate methods for clinical decision-making. It has played an increasingly significant role in the diagnosis and management of liver diseases. Over the last decade, it has been proven safe and effective to use 3D simulation software for pre-hepatectomy assessment, virtual hepatectomy, and measurement of liver volumes in blood flow areas of the portal vein; meanwhile, the use of 3D models in combination with hydrodynamic analysis has become a novel non-invasive method for diagnosis and detection of portal hypertension. We herein describe the progress of research on 3D visualization, its workflow, current situation, challenges, opportunities, and its capacity to improve clinical decision-making, emphasizing its utility for patients with liver diseases. Current advances in modern imaging technologies have promised a further increase in diagnostic efficacy of liver diseases. For example, complex internal anatomy of the liver and detailed morphological features of liver lesions can be reflected from CT-based 3D models. A meta-analysis reported that the application of 3D visualization technology in the diagnosis and management of primary hepatocellular carcinoma has significant or extremely significant differences over the control group in terms of intraoperative blood loss, postoperative complications, recovery of postoperative liver function, operation time, hospitalization time, and tumor recurrence on short-term follow-up. However, the acquisition of high-quality CT images and the use of these images for 3D visualization processing lack a unified standard, quality control system, and homogeneity, which might hinder the evaluation of application efficacy in different clinical centers, causing enormous inconvenience to clinical practice and scientific research. Therefore, rigorous operating guidelines and quality control systems need to be established for 3D visualization of liver to develop it to become a mature technology. Herein, we provide recommendations for the research on diagnosis and management of 3D visualization in liver diseases to meet this urgent need in this research field.


Asunto(s)
Imagenología Tridimensional , Hepatopatías/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Humanos , Hepatopatías/cirugía
16.
Mol Med Rep ; 20(2): 1846-1856, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31257536

RESUMEN

Dysregulation of microRNA­3613­3p (miR­3613­3p) was previously reported in endothelial cells (ECs) during heat stress. The aim of the present study was to investigate the precise role of miR­3613­3p in heat stress. In the present study, potential gene targets of miR­3613­3p in heat­treated ECs were assessed, and the potential effects of miR­3613­3p were determined using Gene Ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify signaling pathways that may be affected by miR­3613­3p in heat­treated cells. Reverse transcription­quantitative PCR, western blotting and annexin V­FITC/propidium iodide staining were performed to detect miRNA expression, protein expression and apoptosis, respectively. Luciferase gene reporter assay was performed to evaluate the association between miR­3613­3p and mitogen­activated protein kinase kinase kinase 2 (MAP3K2). Bioinformatics analysis revealed 865 potential gene targets for miR­3613­3p and a series of functions and pathways in heat­treated ECs. 'Negative regulation of apoptotic process' was identified as a potential function of miR­3613­3p. In addition, functional analysis confirmed the downregulated expression levels of miR­3613­3p in ECs during heat stress, which was accompanied by an increase in apoptosis; restoration of miR­3613­3p expression inhibited apoptosis. MAP3K2 protein was demonstrated to be upregulated in heat­treated ECs, and overexpression of miR­3613­3p reduced MAP3K2 expression levels. Additionally, MAP3K2 was targeted by miR­3613­3p. These results indicated that miR­3613­3p may have complicated roles in ECs under heat stress. miR­3613­3p may serve an important role in the apoptosis of heat­treated ECs, and this effect may be partly achieved by targeting MAP3K2.


Asunto(s)
Apoptosis/genética , Respuesta al Choque Térmico/genética , MAP Quinasa Quinasa Quinasa 2/genética , MicroARNs/genética , Proliferación Celular/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Regulación de la Expresión Génica/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Transducción de Señal
17.
Oncotarget ; 9(24): 17141-17148, 2018 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-29682211

RESUMEN

In this meta-analysis, we analyzed case-control studies that assessed the prognostic potential of miRNAs in cervical cancer. We comprehensively searched EMBASE and PubMed databases and enrolled seven studies with 445 cervical cancer cases. A fixed effects model was used to calculate pooled hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) from the overall survival (OS) data. Our analysis showed that poor OS in cervical cancer was associated with low miR-125 expression (HR = 1.61, 95% CI: 1.02-2.55, P = 0.042; I2 = 10.1%, P = 0.292; n = 99), low miR-145 expression (HR = 1.70, 95% CI: 1.29-2.24, P < 0.001; I2 = 0%, P = 0.560; n = 193) and high miR-196 expression (HR = 0.28, 95% CI: 0.15-0.52, P < 0.001; I2 = 0%, P = 0.950, n = 197). This makes microRNAs such as miR-125, miR-145 and miR-196 potential prognostic biomarkers in cervical cancer.

18.
Zhonghua Wai Ke Za Zhi ; 45(1): 50-3, 2007 Jan 01.
Artículo en Zh | MEDLINE | ID: mdl-17403292

RESUMEN

OBJECTIVE: To investigate the gene differential expression patterns in hepatocirrhosis and non-hepatocirrhosis tissues within different ischemic time. METHODS: The liver tissues were divided into two groups: Group A (non-hepatocirrhosis), Group B (hepatocirrhosis), each of which consisted of 3 groups with different ischemic time: 15, 30 and 45 minutes. The gene differential expression patterns in the two groups within different ischemic time were detected and compared with those in normal liver tissues by using 4000 points gene microarray. RESULTS: In non-hepatocirrhosis tissues, the homeostatic maintenance genes expressed highly during hepatic ischemia for 15 minutes, and no apoptotic gene was expressed; but in hepatocirrhosis tissues, many apoptotic genes expressed highly. As for 30 minutes, in both two groups liver tissue genes expressed to the peak, and the genes related to cell death, oxidative stress and nuclear factors expressed highly. The difference lies in the facts that in Group B pro-apoptosis genes expressed more than those in Group A, and the Ratio values were higher than those in Group A. Many genes of heat shock protein family and antioxidant proteins expressed highly simultaneously in Group A, but comparatively low in Group B. As for 45 minutes, genes of heat shock proteins and antioxidant proteins expressed lowly in Group B. CONCLUSIONS: It suggests that the safe time limit of hepatic ischemia for cell survive is 30 minutes or so. Non-hepatocirrhosis tissues could endure 30 minutes of ischemia and even longer, but it should be restricted within 30 minutes in hepatocirrhosis tissues.


Asunto(s)
Perfilación de la Expresión Génica , Isquemia/genética , Cirrosis Hepática/genética , Hígado/irrigación sanguínea , Humanos , Hígado/metabolismo , Cirrosis Hepática/patología , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Factores de Tiempo
19.
Oncol Lett ; 14(6): 7571-7576, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29344203

RESUMEN

Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types, including hepatocellular carcinoma (HCC) and contributes to chemoresistance of tumor cells. The aim of the present study was to evaluate the possible implication of MUC1 in radioresistance of HCC cells and the underlying mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC cells following irradiation exposure, which was coupled with increased phosphorylation of signal transducer and activator of transcription 3 (STAT3). Enforced expression of MUC1 significantly (P<0.05) promoted the clonogenic survival of HCC cells following irradiation compared with empty vector-transfected cells. MUC1 overexpression resulted in >60% reduction in apoptosis induced by irradiation, as determined by Annexin-V/propidium iodide double staining and flow cytometry analysis. Furthermore, overexpression of MUC1 significantly (P<0.05) attenuated the activation of caspase-3 and poly (ADP-ribose) polymerase in response to irradiation exposure. Mechanistically, MUC1 inhibited irradiation-induced apoptosis through activation of janus kinase 2 (JAK2) and STAT3, and induction of anti-apoptotic proteins induced myeloid leukemia cell differentiation protein Mcl-1 (Mcl-1) and BCL2 like 1 (Bcl-xL). Small hairpin RNA-mediated knockdown of STAT3 or MUC1 resensitized MUC1-overexpressing cells to irradiation-induced apoptosis, which was accompanied by reduced expression of Bcl-xL and Mcl-1. Collectively, MUC1 contributes to radioresistance of HCC cells likely through activation of the JAK2/STAT3 signaling pathway and thus represents a potential target for improving radiotherapy against HCC.

20.
Oncotarget ; 8(35): 59609-59617, 2017 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-28938664

RESUMEN

This study was designed to identify the prognostic value of early response to neoadjuvant chemotherapy (NACT) for long-term survival of cervical cancer patients. We searched Pubmed and EMBASE for studies published through July 2016 on outcomes of cervical patients that received NACT. Eight studies involving 825 cervical cancer patients were ultimately included in our meta-analysis. We pooled the hazard ratios (HR) according to random-effects models and used funnel plots with Egger's and Begg's tests to explore potential publication bias. The HR between early response and 1-year overall survival (OS) was 3.60 (95% CI 1.93-6.72; I2 = 0). Similar results were found in the analysis of 3-year OS (HR 3.34; 95% CI 2.28-4.90; I2 = 0) and 5-year OS (HR 3.44; 95% CI 2.40-4.94; I2 = 0). Sensitivity analysis showed that all of the pooled results were robust, and all logHRs had confidence limits > 0. Our findings indicate that early response is associated with long-term survival, and responders achieved a higher survival rate than non-responders.

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