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With a global rise in morbidity rates, obesity has become a pressing public health issue. With increased adipocyte number and volume as the main characteristics, obesity is also manifested by metabolic disorders to varying degrees. At the same time, obesity is a risk factor for diabetes, hypertension, stroke, cancer, and cardiovascular diseases, imposing burdens on society and families. Influenced by lifestyle, environment, behavior, and genetics, obesity is caused by the interaction of many factors, and its pathological process is complex, involving inflammation, autophagy, and intestinal dysbiosis. The mitogen-activated protein kinase (MAPK) cascade reaction, a pivotal signaling pathway, plays a crucial role in cellular processes such as proliferation, differentiation, apoptosis, and stress responses. Both Chinese and international studies indicate that the MAPK signaling pathway can effectively regulate obesity through various pathways, including the modulation of adipocyte differentiation and apoptosis, appetite control, and inflammation improvement. Moreover, traditional Chinese medicine (TCM) has demonstrated significant efficacy in preventing and treating obesity, leveraging advantages such as multiple targets, diverse components, and minimal adverse effects. Research indicates that the MAPK signaling pathway is a primary focus of TCM regulation in this context, although a systematic review in this field is currently lacking. Therefore, this paper, by reviewing the latest Chinese and international research, provided a concise overview of the basic structure of the MAPK pathway, with a specific emphasis on recent progress in TCM interventions targeting the MAPK pathway for obesity treatment. The results indicate that regulating adipose tissue formation, differentiation, and thermogenesis, reducing inflammation and oxidative stress levels, and improving insulin sensitivity and metabolic disorders seem to be the main ways for TCM to regulate the MAPK pathway to prevent and treat obesity. However, it is necessary to find more research methods and explore potential mechanisms underlying TCM formulations based on the MAPK pathway for obesity prevention and treatment.
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In this study we investigated whetherL-cysteine (L-cys) could alleviate LPS-induced intestinal disruption and its underlying mechanism. Piglets fed with anL-cys-supplemented diet had higher average daily gain.L-cys alleviated LPS-induced structural and functional disruption of intestine in weanling piglets, as demonstrated by higher villus height, villus height (VH) to crypt depth (CD) ratio, and transepithelial electrical resistance (TER) and lower FITC-dextran 4 (FD4) kDa flux in jejunum and ileum. Supplementation withL-cys up-regulated occludin and claudin-1 expression, reduced caspase-3 activity and enhanced proliferating cell nuclear antigen expression of jejunum and ileum relative to LPS group. Additionally,L-cys suppressed the LPS-induced intestinal inflammation and oxidative stress, as demonstrated by down-regulated TNF-α, IL-6 and IL-8 mRNA levels, increased catalase, superoxide dismutase, glutathione peroxidase activity, glutathione (GSH) contents and the ratio of GSH and oxidized glutathione in jejunum and ileum. Finally, a diet supplemented withL-cys inhibited NF-κB(p65) nuclear translocation and elevated NF erythroid 2-related factor 2 (Nrf2) translocation compared with the LPS group. Collectively, our results indicated the protective function ofL-cys on intestinal mucosa barrier may closely associated with its anti-inflammation, antioxidant and regulating effect on the NF-κB and Nrf2 signaling pathways.
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Cisteína/uso terapêutico , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Animais , Suplementos Nutricionais , Inflamação/induzido quimicamente , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Lipopolissacarídeos/imunologia , Estresse Oxidativo/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Treating dentofacial deformities secondary to condylar resorption is a remarkable clinical challenge. Combined orthodontic treatment and orthognathic surgery is currently the main treatment scheme and is often integrated with temporomandibular joint surgery or conservative treatment according to the severity of condylar resorption. This paper discussed the etiology, clinical features, imaging features, treatment options, and prophylaxis of condylar resorption.
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Humanos , Reabsorção Óssea , Deformidades Dentofaciais , Côndilo Mandibular , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Articulação TemporomandibularRESUMO
Weaning is the most significant event in the life of pigs and is always related with intestinal disruption. Although it is well known that zinc oxide (ZnO) exerts beneficial effects on the intestinal barrier, the mechanisms underlying these effects have not yet been fully elucidated. We examined whether ZnO protects the intestinal barrier via mitogen-activated protein kinases and TGF-ß1 signaling pathways. Twelve barrows weaned at 21 d of age were randomly assigned to two treatments (0 verus 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that supplementation with ZnO increased daily gain and feed intake, and decreased postweaning scour scores. ZnO improved intestinal morphology, as indicated by increased villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by increased transepithelial electrical resistance and decreased mucosal-to-serosal permeability to 4-ku FITC dextran. ZnO decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38), while it increased the ratio of ERK (p-ERK/ERK). Supplementation with ZnO increased intestinal TGF-ß1 expression. The results indicate that supplementation with ZnO activates ERK ½, and inhibits JNK and p38 signaling pathways, and increases intestinal TGF-ß1 expression in weaned pigs.
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Suplementos Nutricionais , Mucosa Intestinal/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Suínos/imunologia , Fator de Crescimento Transformador beta1/metabolismo , Óxido de Zinco/administração & dosagem , Animais , Permeabilidade da Membrana Celular/efeitos dos fármacos , Impedância Elétrica , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Mucosa Intestinal/efeitos dos fármacos , MAP Quinase Quinase 4/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Regulação para Cima , Desmame , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
This study explored whether zinc oxide (ZnO) supplementation could alleviate weanling-induced intestinal injury through TLR and NOD-like receptor signaling pathways. Twelve early-weanling piglets were allotted to two dietary treatments (control vs 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that supplemental ZnO improved daily gain and feed intake, decreased post weaning scour scores, increased villus height and villus height:crypt depth ratio at the jejunal mucosa, and decreased diamine oxidase activity and endotoxin concentration in plasma. The intestinal mRNA levels of TLR4 and its downstream signals, including MyD88, IL-1 receptor-associated kinase 1 and TNF-α receptor-associated factor 6, were decreased, and the expressions of intestinal pro-inflammatory cytokines and chemokines were decreased simultaneously in the ZnO-supplemented piglets. Although NF-κB p65 mRNA abundance was not affected by ZnO supplementation, NF-κB p65 protein expression was down-regulated by ZnO. However, ZnO supplementation had no effect on intestinal expressions of NOD1 and NOD2, and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2, as well as protein expressions of caspase-3 and heat shock protein 70. The results indicated that the protective effects of ZnO on intestinal integrity were closely related to decreasing the expressions of genes associated with inflammation through inhibiting the TLR4-MyD88 signaling pathways.
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Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Óxido de Zinco/farmacologia , Animais , Quimiocinas/biossíntese , Citocinas/biossíntese , Dieta , Regulação para Baixo/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , RNA Mensageiro/biossíntese , Sus scrofa , Suínos , Fator de Transcrição RelA/biossínteseRESUMO
Weaning stress caused marked changes in intestinal structure and function. Transforming growth factor-ß1 (TGF-ß1) and canonical Smads signaling pathway are suspected to play an important regulatory role in post-weaning adaptation of the small intestine. In the present study, the intestinal morphology and permeability, developmental expressions of tight junction proteins and TGF-ß1 in the intestine of piglets during the 2 weeks after weaning were assessed. The expressions of TGF-ß receptor I/II (TßRI, TßRII), smad2/3, smad4 and smad7 were determined to investigate whether canonical smads signaling pathways were involved in early weaning adaption process. The results showed that a shorter villus and deeper crypt were observed on d 3 and d 7 postweaning and intestinal morphology recovered to preweaning values on d 14 postweaning. Early weaning increased (P<0.05) plasma level of diamine oxidase (DAO) and decreased DAO activities (P<0.05) in intestinal mucosa on d 3 and d 7 post-weaning. Compared with the pre-weaning stage (d 0), tight junction proteins level of occludin and claudin-1 were reduced (P<0.05) on d 3, 7 and 14 post-weaning, and ZO-1 protein was reduced (P<0.05) on d 3 and d 7 post-weaning. An increase (P<0.05) of TGF-ß1 in intestinal mucosa was observed on d 3 and d 7 and then level down on d 14 post-weaning. Although there was an increase (P<0.05) of TßR II protein expression in the intestinal mucosa on d3 and d 7, no significant increase of mRNA of TßRI, TßRII, smad2/3, smad4 and smad7 was observed during postweaning. The results indicated that TGF-ß1 was associated with the restoration of intestinal morphology and barrier function following weaning stress. The increased intestinal endogenous TGF-ß1 didn't activate the canonical Smads signaling pathway.
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Intestinos/anatomia & histologia , Intestinos/fisiologia , Proteínas Smad/metabolismo , Suínos/fisiologia , Fator de Crescimento Transformador beta1/metabolismo , Desmame , Animais , RNA Mensageiro/genética , Transdução de Sinais , Proteínas Smad/genética , Fator de Crescimento Transformador beta1/análiseRESUMO
Objective To investigate the level and clinical significance of D-dimer(D-D) and fibrinogen(Fib) in patients with first-episode schizophrenia.Methods The 83 patients with first-episode schizophrenia from March 2014 to December 2016 were selected as the study group,meanwhile 58 healthy subjects without mental illness and major somatic diseases were selected as control group.Two groups of subjects were collected from fasting sodium citrate anticoagulated plasma to detect level of D-D and Fib.Resuits The level of D-D in the first-episode schizophrenia group was(240.42±245.78)μg/L,which was significantly higher than that in the control group(76.53±71.25)μg/L,and the difference was statistically significant(P<0.05).While the level of Fib in the first-episode schizophrenia group (2.62 ± 0.49) g/L was significantly lower than that of the control group (2.87 ± 0.65) g/L,and the difference was statistically significant(P<0.05).The increase in D-D levels and the reduction in Fib levels in patients with firstepisode schizophrenia were not related to gender.Conclusion he patients with first-episode schizophrenia in acute stage may have hypercoagulable status and secondary fibrinolysis.
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Objective To investigate the level and clinical significance of D-dimer(D-D) and fibrinogen(Fib) in patients with first-episode schizophrenia.Methods The 83 patients with first-episode schizophrenia from March 2014 to December 2016 were selected as the study group,meanwhile 58 healthy subjects without mental illness and major somatic diseases were selected as control group.Two groups of subjects were collected from fasting sodium citrate anticoagulated plasma to detect level of D-D and Fib.Resuits The level of D-D in the first-episode schizophrenia group was(240.42±245.78)μg/L,which was significantly higher than that in the control group(76.53±71.25)μg/L,and the difference was statistically significant(P<0.05).While the level of Fib in the first-episode schizophrenia group (2.62 ± 0.49) g/L was significantly lower than that of the control group (2.87 ± 0.65) g/L,and the difference was statistically significant(P<0.05).The increase in D-D levels and the reduction in Fib levels in patients with firstepisode schizophrenia were not related to gender.Conclusion he patients with first-episode schizophrenia in acute stage may have hypercoagulable status and secondary fibrinolysis.
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Objective:To evaluate the effectiveness of Xipayi Mouth Rinse in the treatment of halitosis.Methods:PubMed/MEDLINE,China National Knowledge Infrastructure (CNKI) (1979-2015) and Weipu Database for Chinese Technical Periodicals (1989-2013) were systemically searched.The methodological quality of the included trials was assessed based on the Jadad scale and the available data were analyzed with RevMan software (version 5.3).Results:8 studies involving 608 participants satisfied the minimum criteria for Meta-analysis.The evidence showed that the Organoleptic Score (OS) of Xipayi Mouth Rinse compared with placebo for treatment of halitosis was [WMD =-0.43,95% CI (-0.57,-0.29)],plaque index (PLI) [WMD =-1.59,95% CI (-1.67,-1.51)];the OS of Xipayi Mouth Rinse compared with western medicine [WMD =0.16,95% CI (0.05,0.28)],PLI [WMD =0.10,95% CI(0.03,0.18)];the total efficiency of Xipayi Mouth Rinse compared with normal saline was[RR:1.64,95% CI(1.11,2.42)].Conclusion:The current clinical evidence showed that the effectiveness of Xipayi Mouth Rinse in the treatment of halitosis is higher than the Placebo,but lower than western medicine.
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BACKGROUND:Insulin analogues have been extensively applied in the treatment of diabetes mellitus.Insulin glargine has a higher affinity for insulin like growth factor 1 receptor compared with human insulin.Further research is needed to ensure whether insulin and its analogues exert same effects on fracture healing in type 2 diabetes mellitus.OBJECTIVE:To observe the osteocalcin expression and callus formation in the healing of fracture in type 2 diabetic rats induced by human insulin and insulin glargine,to observe the difference between two treatment methods,and to explore the related mechanisms.METHODS:Sixty-four Sprague-Dawley rats were randomly assigned into human insulin group (group A),insulin glargine group (group B),diabetes mellitus group (group C) and control group (group D).Rats in the groups A,B and C were fed with high-sugar and high-fat diet for 4 weeks followed by intraperitoneal injection of small-dosage streptozotocin twice,to establish the rat models of type 2 diabetes mellitus.After the right tibia of each rat was broken,insulin glargine and Novolin 30R were used in the groups A and B,respectively.Fracture healing was observed on X-ray,callus formation and number of osteoblasts were observed by microscope,and serum level of osteocalcin was measured by ELISA method at 1,2,4,and 6 weeks after modeling.RESULTS AND CONCLUSION:X-ray results revealed better fracture healing in the groups A,B and D than the group C.Osteoblast proliferation in callus was significantly better in the groups A,B and D than in the group C.Serum level of osteocalcin in each group was on the rise,which was significantly higher in the groups A,B and D than the group C (P < 0.05),but had no significant difference among groups A,B and D (P > 0.05).In summary,insulin glargine can increase the serum level of osteocalcin,accelerate the callus formation,and improve the healing of fracture in type 2 diabetic rats.Furthermore,there is no significant difference in the therapeutic efficacy between insulin glargine and human insulin.
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BACKGROUND:Previous studies have shown that traumatic brain injury can promote the regeneration of peripheral nerve by reducing scar collagen in nerve endings.OBJECTIVE:To investigate the effect of brain injury at different locations on the ipsilateral rat sciatic nerve regeneration.METHODS:Ninety-nine healthy male Sprague-Dawley rats were equivalently randomized into three groups:group A,right sciatic nerve transection;group B,right sciatic nerve transection combined with right brain injury;and group C,right sciatic nerve transection combined with left brain injury.All of transected nerves were sutured under microscope.Classical Feeney method was used to establish a model of traumatic brain injury.At 4,6,8,10 and 12 weeks after modeling,the sciatic functional index (SFI) was calculated by measuring footprint.At 4,8 and 12 weeks after modeling,the bilateral gastrocnemius were harvested for determining wet weight and calculate wet weight ratio,followed by acetylcholinesterase staining at the motor end plate to detect the absorbance values.At 4,8 and 12 weeks after modeling,fluoro-gold retrograde tracing was used to trace L4-5 vertebrae for 1 week,and the number of spinal cord anterior horn motor neurons positive for fluoro-gold was detected and calculated by fluorescence microscope.RESULTS AND CONCLUSION:The SFI value in each group was gradually improved with time.The SFI value was significantly higher in the groups B and C than the group A at 4 and 6 weeks after modeling (P < 0.05),and was further improved in the group B at 8 weeks compared with the groups A and C (P < 0.05).The wet weight ratio of gastrocnemius showed no significant difference among groups at 4 weeks after modeling (P > 0.05),and the group B showed a significantly higher wet weight ratio than the other groups from the 8th week (P < 0.05).Compared with the groups A and C,the absorbance values of motor endplate in group B appeared to be a significant increase at the beginning of the 8th week (P < 0.05).At 4 and 6 weeks after modeling,the number of spinal cord anterior horn motor neurons positive for fluoro-gold was significantly nigher in the groups B and C than in the group A,and the number was significantly higher in the group B than the groups A and C at 12 weeks (all P < 0.05).These finding manifest that brain injury can promote the repair of ipsilateral sciatic nerve injury,thus proving theoretical reference for unveiling the mechanism by which traumatic brain injury promotes peripheral nerve regeneration.
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This study was to investigate the effect of annexin A5 on testosterone secretion from primary rat Leydig cells and the underlying mechanisms. Isolated rat Leydig cells were treated with annexin A5. Testosterone production was detected by chemiluminescence assay. The protein and mRNA of Steroidogenic acute regulatory (StAR), P450scc, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and 17α-hydroxylase were examined by Western blotting and semi-quantitative RT-PCR, respectively. Annexin A5 significantly stimulated testosterone secretion from rat Leydig cells in dose- and time-dependent manners and increased mRNA and protein expression of StAR, P450scc, 3β-HSD, and 17β-HSD but not 17α-hydroxylase. Annexin A5 knockdown by siRNA significantly decreased the level of testosterone and protein expression of P450scc, 3β-HSD, and 17β-HSD. The significant activation of ERK1/2 signaling was observed at 5, 10, and 30 min after annexin A5 treatment. After the pretreatment of Leydig cells with ERK inhibitor PD98059 (50 μmol l-1 ) for 20 min, the effects of annexin A5 on promoting testosterone secretion and increasing the expression of P450scc, 3β-HSD, and 17β-HSD were completely abrogated (P < 0.05). Thus, ERK1/2 signaling is involved in the roles of annexin A5 in mediating testosterone production and the expression of P450scc, 3β-HSD, and 17β-HSD in Leydig cells.
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Objective To discuss the clinical application and efficacy of digitization prototyping titanium meshes in the repairing of earthquake-induced skull defect. Methods The clinical data of 66patients with skull defect caused by earthquake were analyzed. These patients were divided into group A (treated with traditional handwork shaping titanium meshes, n=1S) and group B (treated with digitization prototyping titanium meshes, n=51). The efficacy and complications were compared.Results Compared to group A, group B had a shorter operation time, a shorter recovery time, a lower postoperative incidence rate of subcutaneous hematocele, hydrops and infection (P<0.05). The digitization prototyping titanium meshes were significantly superior to handwork shaping titanium meshes (P<0.05). And patients with skull defect repaired at early stage had a higher recovery rate of neurological function than those at advanced stage (P<0.05). Conclusion Using digitization prototyping titanium meshes to repair the skull defect can enjoy anatomical reduction, shortened operation time, and fewer postoperative complications. In addition, an early repair in earthquake-induced skull defect can not onlydisburden patients' mind, but also prevent or even reverse secondary brain damage of skull defect,therefore, the patients' neurological function can be improved and their lives can be better.
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Objective To in ve stigate the effects of advanced glycation end products (AGEs) on matrix metallop roteinase-2 (MMP-2) activity and its mRNA expression in renal cortex of rats. Methods Diabetic model of rats was induced by s treptozotocin. AGEs were prepared by incubation of rat serum protein with 0.5 mo l/L glucose. AGEs was administered intravenously to normal rats (AGEs group), an d native rat serum protein was given as negative control (negative group) and no rmal rats without treatment were as control (control group). AGEs content in ren al cortex and serum was quantified by ELISA, MMP-2 and TIMP-2 mRNA expressions were examined by RT-PCR and MMP-2 activity was measured by zymography. Results AGEs content increased significantly, MMP-2 mRNA expression descended and TIMP-2 mRNA expression ascended in renal cortex o f diabetic rats (all P
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A procedure for the preparation of PCR template from Saccharomyces cerevisiae using boiling method is described,and arg-13 gene from low copy ARSCEN plasmid and ymc1 gene from genomic DNA are amplified with high efficiency respectively.