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Objective To characterize the species of invasive Pomacea snails that were discovered for the first time in Shandong Province. Methods Pomacea snails samples were collected in the field of Jining City, Shandong Province on October 2021 for morphological identification. Pomacea snails were randomly sampled and genomic DNA was extracted from foot muscle tissues of Pomacea snails for multiplex PCR amplification. The PCR amplification product was sequenced. Then, the sequence was aligned and a phylogenetic tree was created using the software MegAlign 7.1.0. In addition, Angiostongylus cantonensis infection was detected in Pomacea snails with the lung microscopy. Results A total of 104 living Pomacea snails were collected, and all were characterized as Pomacea spp. based on morphological features. Of 12 randomly selected adult Pomacea snails, multiplex PCR assay and sequencing identified eleven snails as P. canaliculata and one as P. maculata. No A. cantonensis infection was detected in 104 Pomacea snails. Conclusion This is the first report of invasive Pomacea snails in Shandong Province, where P. canaliculata and P. maculata are found.
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ObjectiveTo explore the effect of Buyang Huanwutang （BHD） on rehabilitation of ischemic stroke（IS） by cell membrane solid-phase chromatography and network pharmacology. MethodCell membrane solid-phase chromatography was performed to screen the specific binding components of BHD with hippocampal neurons. Targets of the specific components were retrieved based on PubChem and PharmMapper and those of IS were searched from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Then， the protein-protein interaction （PPI） network was constructed with STRING and Cytoscape 3.7.1， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the hub genes in the PPI network. Thereby， the mechanism of BHD in promoting IS rehabilitation was clarified. ResultA total of 13 specific components were identified. The hub genes were mainly involved in the biological processes of regulation of cell proliferation， protein phosphorylation， hypoxia response， and angiogenesis， and the pathways of Forkhead box O （FoxO） signaling pathway， adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK） signaling pathway， nuclear factor kappa B （NF-κB） signaling pathway， and apoptosis pathway. ConclusionBHD may promote the recovery of IS by regulating FoxO， AMPK， NF-κB， and apoptosis pathways.
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Objective: To observe the efficacy of mild moxibustion combined with functional exercise in the treatment of upper-limb lymphedema after breast cancer surgery and its effect on serum vascular endothelial growth factor C (VEGF-C). Methods: Seventy-eight patients were divided into a control group and an observation group by the random number table method, with 39 cases in each group. The control group received functional exercise and the observation group received mild moxibustion plus functional exercise. The differences in circumference between the two upper limbs, the lymphatic flow of the affected upper limb, the disability of arm, shoulder and hand (DASH) score, the functional assessment of cancer therapy-breast (FACT-B) score and serum VEGF-C level between the two groups were compared before and after treatment. Efficacy was evaluated after treatment. Results: The total effective rate was significantly higher in the observation group than in the control group (P<0.05). The difference in circumference between the two upper limbs of the two groups decreased significantly after treatment (both P<0.05), but it was significantly lower in the observation group than in the control group (P<0.05). The lymphatic flow of the affected upper limb of the two groups increased significantly after treatment (both P<0.05), but it was significantly greater in the observation group than in the control group (P<0.05). The DASH scores of the two groups decreased significantly after treatment (both P<0.05), but it was significantly lower in the observation group than in the control group (P<0.05). The FACT-B scores of the two groups increased significantly after treatment (both P<0.05), but it was significantly higher in the observation group than in the control group (P<0.05). After treatment, the serum VEGF-C level increased significantly in the observation group (P<0.05), whereas the control group did not show significant change (P>0.05). The post-treatment serum VEGF-C level was significantly higher in the observation group than in the control group (P<0.05). Conclusion: The efficacy of mild moxibustion combined with functional exercise for upper-limb lymphedema after breast cancer surgery is certain, which can reduce the difference in circumference between the two upper limbs, increase the lymphatic flow of the affected upper limb, improve the limb function and the quality of life, and regulate the serum VEGF-C level.
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Objective To investigate the prevalence and changing trend of Enterobius vermicularis infections among children in Shandong Province, so as to provide the scientific evidence for the adjustment and development of the enterobiasis control strategy. Methods Soil-borne nematodiasis surveillance sites were assigned in 51 counties (districts, cities) in Shandong Province from 2016 to 2020, and the E. vermicularis infections were detected using a modified Kato-Katz technique and the cellophane tape method among children at ages of 3 to 9 years living in these surveillance sites. The epidemiological profiles of E. vermicularis-infected children were descriptively analyzed. Results A total of 5 060 children at ages of 3 to 9 years were detected in 51 soil-borne nematodiasis surveillance sites in Shandong Province from 2016 to 2020, and the overall prevalence of E. vermicularis infections was 2.23%. The annual prevalence of E. vermicularis infections was 3.99% (26/651), 1.70% (14/824), 0.96% (8/837), 2.90% (45/1 552) and 1.67% (20/1 196) from 2016 to 2020, respectively, with a significant difference detected among years ( χ2 = 21.455, P < 0.01). The prevalence of E. vermicularis infections was 1.25% (15/1 198), 1.85% (14/755), 3.18% (84/2 640) and 0 (0/467) among children from central, eastern, southern and northern Shandong Province (χ2 = 27.326, P < 0.01). In addition, there was no significant difference in the prevalence of E. vermicularis infections between male (1.98%, 56/2 831) and female children (2.56%, 57/2 229) (χ2 = 1.916, P > 0.05); however, there was age-specific prevalence of E. vermicularis infections among children (χ2 = 16.448, P < 0.05), with the greatest prevalence detected among children at ages of 6 years (3.18%, 25/786), and the lowest prevalence seen among children at ages of 3 years (0.75%, 6/800). Conclusions The prevalence of E. vermicularis infections remained at a medium level among children at ages of 3 to 9 years in Shandong Province from 2016 to 2020, with region-specific prevalence found across the province. An integrated strategy is required for enterobiasis control.
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Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.
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Aged , Humans , Male , Middle Aged , Diuretics/therapeutic use , Furosemide/therapeutic use , Heart Failure/drug therapy , Stroke Volume , UltrafiltrationABSTRACT
ObjectiveTo investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. MethodsFrom 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. Results The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. Conclusions There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.
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To investigate the effects of miR-31 on TLR4/NF-κB signaling pathway and apoptosis-related proteins in dextran sulfate sodium (DSS) induced mouse colon colitis. Methods: ① Mouse model of colon colitis: 1% DSS was used to induce mouse ulcerative colitis (UC). Fourteen FVB non-transgenic mice were randomly divided into control group (n= 6), DSS group (n= 8), and 16 FVB miR-31 transgenic mice were randomly divided into miR-31 overexpression group (n= 8), miR-31 overexpression +DSS group (n= 8). DSS was dissolved in water and administered to mice by drinking water. The DSS group and miR-31+DSS group drank 1% DSS water in the first week, normal sterilized water in the second week, and 1% DSS water in the third week, after 5 weeks, the modeling was completed, then the colon tissues of the mice were collected. Western blot and IHC were used to detect the expressions of NF-κB p65, TLR4, Bax and Bcl-2 proteins in mouse colon tissue, TUNEL was used to detect apoptosis of mouse colon tissues. ② Cell culture experiments: Transfection of miR-31mimic and inhibitor by lipofectamine resulted in overexpression or knockdown of miR-31 in human colon epithelial cell line HCT 116 cells, each group was repeated three times and cells were collected 48 h later, Western blot was used to detect the expressions of NF-κB p65 and TLR4 protein. ① In animal experiments, compared with the control group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the DSS group and miR-31 overexpression group in mouse colon tissue were significantly increased (P＜0.05 or P＜0.01), and the Bcl-2 / Bax ratio was significantly reduced (P＜0.05 or P＜0.01); and compared with the DSS group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the miR-31+DSS group were significantly increased (P＜0.01), while the Bcl-2/Bax ratio was significantly decreased (P＜0.01). ② In cell experiments, compared with the control group, the expression levels of NF-κB p65 and TLR4 protein in the over-expressed miR-31 group of HCT 116 cells were significantly increased (P＜0.05 or P＜0.01), the expressions of NF-κB p65 and TLR4 protein in miR-31 knockdown group were decreased (P＜0.05). miR-31 promotes the development of colitis by promoting TLR4/NF-κB signaling pathway and mediating apoptosis of intestinal epithelial cells.
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The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1β, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1β, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.
Subject(s)
Animals , Male , Mice , Caspase 1 , Gene Expression , Hippocampus , Inflammasomes , Insulin Resistance , Mice, Inbred C57BL , NIMA-Related Kinases , NLR Family, Pyrin Domain-Containing 3 Protein , Physical Conditioning, Animal , PyroptosisABSTRACT
Objective:To investigate the effects of Buyang Huanwu Tang （BHT） on axonal regeneration and neurological rehabilitation of the rats suffering ischemic stroke （IS）. Method:A total of 180 SD rats were used to establish a middle cerebral artery infarction （MCAO） model. The animals that were successfully modeled were randomly divided into model group， BHT group （12 g·kg-1） and nimodipine group （20 mg·kg-1）， and a sham group was established， with 28 rats in each group. After seven-days intragastric administration of BHT， the animals were sacrificed. TTC staining was used to test cerebral infarction. Brain water content was measured to observe cerebral edema. Bielschowsky's silver staining and immunofluorescence were performed to observe axonal degeneration and the protein expression of neurofilament protein-200（NF-200）. Quantitative real-time polymerase chain reaction （PCR） was used to analyze the mRNA expression of repulsion oriented molecule a （RGMa）， Ras homologous enzyme （Rho）， Rho kinase （ROCK）， and collapsion response regulatory protein 2 （CRMP2）. Neurological function scores assay was used to examine neurological recovery. Result:Compared with sham group， the cerebral infarction volume and brain water content increased significantly（P<0.01）， and motor function was markablely decreased in the model group. Axonal degeneration and nerve fiber damage were obviously observed. Also， gene expression of axon growth-related protein was deviation from normal （P<0.01）. Compared with model group， the cerebral infarction rate （P<0.01）， brain water content （P<0.01） and axonal degeneration of BHT group and nimodipine group were significantly reduced. The expression of NF-200 was increased. Also， the mRNA expression of RGMa， Rho and ROCK was lower （P<0.05） while the mRNA expression of CRMP2 was higher （P<0.01）. And the neurological function was significantly improved （P<0.05）. Conclusion:BHT can promote axon regeneration after ischemic stroke injury by regulating the mRNA expression of axon growth-related protein， thereby improving nerve function.
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OBJECTIVE@#To investigate the expression of C/EBPα gene in elderly patients with multiple myeloma （MM） and its prognostic significance.@*METHODS@#Sixty-nine olderly patients with multiple myeloma (MM) treated in our hospital from February 2015 to October 2017 were selected and enrolled in the MM group, 38 healthy persons received physical examination were selected and enrolled in the control group. The bone marrow of 2 groups was collected and the mononuclear cells were isolated.The mRNA expression level of C/EBPα gene in mononuclear cells was determined by RT-PCR, the Western blot was used to detect the protin expression level of PBMNC C/EBPα, and the protein level of C/EBPα in bone marrow was detected by immunohistochemistry. The correlations of C/EBPα gene expression with the clinical characteristics and survival time in MM patients were analyzed.@*RESULTS@#The expression level of mRNA and protein of C/EBPα in MM patients was significantly lower than that in the control group (P0.05).Immunohistochemical staining showed that the bone marrow samples of the control group were stained more deeply, and the staining intensity in bone marrow samples of MM patients with CR, PR and relapse was successively descended. The protein level of C/EBPα in CR patients with MM was significantly higher than that in PR and relapsed patients by Western blot (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in the patients with high expression of C/EBPα gene were higher than those in low expression group (P<0.05). Multivariate Cox regression analysis showed that CRP,ratio of myeloma cells and C/EBPα gene were independent factors affecting OS and PFS (P<0.05).@*CONCLUSION@#The expression level of C/EBPα gene in MM patients is low that may stimulate the genesis of MM, and the expression of C/EBPα gene closely relates with the development of MM disease.
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Aged , Humans , Bone Marrow , CCAAT-Enhancer-Binding Protein-alpha , Multiple Myeloma , Genetics , Neoplasm Recurrence, Local , PrognosisABSTRACT
Dysphagia can lead to multiple complications, increasing mortality and recurrence, and affecting the quality of life. Mendelsohn maneuver is a kind of physical therapy to improve the safety and effectiveness of swallowing. This paper introduced the origin of Mendelsohn maneuver, its physiological mechanism and clinical application. The potential risks and shortcomings of Mendelsohn maneuver were discussed, and a new solution was put forward.
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Objective:To explore the effect of standardized patients stimulation combined with microteaching method in clinical teaching practice of students majored in rehabilitation therapy. Methods:From March, 2017 to March, 2018, 47 students majored in rehabilitation therapy in our department were selected with convenience sampling. Then they were randomly divided into control group (n = 23) and experimental group (n = 24). The control group received routine teaching method, while the experimental group received standardized patients stimulation combined with microteaching method. Their theoretical achievement, practical skills achievement and feedback on teaching effect were compared after this course. Results:The theoretical scores and practical skills scores were higher in the experimental group than in the control group (t > 2.366, P < 0.05). Meanwhile, the scores were higher in the experimental group than in the control group in the following aspects: the design capability of rehabilitation treatment program, the capability of selection of rehabilitation assessment tools, the communication and expression ability, learning enthusiasm and initiative, and the ability to relate theory to practice (t > 2.082, P < 0.05). Conclusion:Standardized patients simulation combined with microteaching method could improve the clinical practice effect of students majored in rehabilitation therapy.
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Objective:To explore the effect of working memory updating training on verbal fluency for patients with motor aphasia. Methods:From June, 2015 to June, 2018, 80 patients with motor aphasia were randomly divided into control group (n = 40) and study group (n = 40). The control group accepted routine speech training, while the study group accepted working memory updating training in addition, for eight weeks. They were assessed updating function and verbal fluency before and after training. Results:The updating function and verbal fluency improved in the study group after training (t > 2.418, P < 0.05), and were better than those in the control group (t > 2.407, P < 0.05). Conclusion:Working memory updating training can improve both speech and cognition for patients with motor aphasia.
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Chronic kidney disease(CKD) has become a global public health problem, deterioration of the disease to end-stage renal disease(ESRD) will bring heavy burdens to individuals, families and society. The essence of CKD is occurrence and development of renal fibrosis led by continuous stimulation of chronic inflammation. Galectin-3(Gal-3) is a multifunctional protein, which can not only regulate the activation of macrophages in inflammatory response, produce cytokines such as transforming growth factor(TGF)-β, promote the occurrence of renal fibrosis, but also regulate the expression of collagen in the process of tissue remodeling, promote renal fibrosis, and play an irreplaceable role in inflammation and fibrosis. Both modified citrus fructose(MCP) and GCS-100 are Gal-3 inhibitors, which can alleviate renal injury to a certain extent and are potential targets for anti-renal fibrosis therapy. However, Gal-3 has been shown to have a protective effect on the kidney. In the early stage of chronic renal injury, the anti-apoptosis effect of Gal-3 can protect glomeruli and tubules from chronic injury. The present paper mainly reviews the role of Gal 3 in renal fibrosis.
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Objective:To analyze and identify the brain and blood absorption components of rats after intragastric administration of Buyang Huanwu Tang(BYHWT). Method:The brain tissue,plasma of normal rats and the cerebral ischemia-reperfusion rats were analyzed by UPLC-Q-TOF-MS/MS.The prototype components in BYHWT were identified according to retention time,accurate relative molecular weight,primary and secondary mass spectrometry data. Result:After the administration of BYHWT,five compounds were found to enter the normal brain tissue through the blood-brain barrier and identified as calycosin-7-glucoside,albiflorin,formononetin-7-O-β-D-glucoside-6″-O-acetyl,safflower yellow A and astragaloside A;two compounds penetrated the blood-brain barrier and entered modeling brain tissue,and they were identified as calycosin-7-glucoside and formononetin-7-O-β-D-glucoside-6″-O-acetyl;seven compounds entered normal plasma and were identified as calycosin-7-glucoside,albiflorin,hydroxysafflor yellow A,et al;three compounds entered model plasma and identified as calycosin-7-O-β-D-glucoside-6″-O-acetyl,6″-O-acetyl-(6αR,11αR)-9,10-dimetho-xypterocarpan-3-O-β-D-glucoside and formononetin-7-O-β-D-glucoside-6″-O-acetyl. Conclusion:BYHWT has different pharmacological material basis in normal and cerebral ischemia-reperfusion rats.
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@#【Objective】To establish a reliable and reproducible mouse model of cisplatin induced inner ear hair cells loss and to make possible for further study of mechanisms of cisplatin-induced ototoxicity in mice from the molecular and genetic aspects. 【Methods】Twenty healthy mice were evenly divided into two groups in random. The mice in group A received a single dose of furosemide（200 mg/kg，intraperitoneal）followed by a single dose of cisplatin（1.0 mg/kg，intraperitoneal）1 h later，and the mice in group B received a single dose of furosemide（200 mg/kg，intraperitoneal）followed by a single dose of cisplatin（0.5 mg/kg，intraperitoneal）1 h later. Auditory brainstem response（ABR）and distortion product otoacoustic emission （DPOAE） were tested in both groups 10 d post the cisplatin-furosemide treatment and bilateral cochlea were taken out and fixed，one side cochlea were used for the surface preparation of total cochlear basal membrane and stained to count the number of cochlear hair cells from apex to base，the other was embedded with EPON 812 gel and then cut into half thin slices. Six mice were used as control group. 【Results】In both groups，the average ABR threshold of mice at each frequency were elevated，while the average DPOAE values were decreased. The average ABR threshold in group A increased significantly and the amplitude of each frequency decreased a lot，and DPOAE in high frequencies vanished；In group B，there was a minor elevation of ABR threshold with a slightly lower amplitude in higher- frequencies（16，20，32 kHz）but no amplitude change in lower frequencies（4，8，12 kHz）both in ABR and DPOAE. The surface preparation of Cochlear results in group A showed that nearly all the outer hair cells in the base had been destroyed，and most were destroyed in the apex；In group B，only the majority of cochlear outer hair cells at the base missed. There was no decrease of the numbers of the inner hair cells in both groups. Semi-thin cross-sections results also showed that the stria vascularis and spiral ganglion cells were close to normal in both groups. 【Conclusion】Co- administration of single dose of 1.0 mg/kg cisplatin with a single dose of 200 mg/kg furosemide may induce significant loss of cochlear outer hair cells in mice.
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OBJECTIVE@#To investigate the protective effects and the possible mechanisms of simvastatin on myocardial injury induced by diabetes.@*METHODS@#Twenty-four SD rats (180~220)g were randomly divided into control group (control, =8) and modeled groups(=16), the modeled groups were injected with streptozotocin intraperitoneally to induce diabetes. Then the modeled rats were randomly divided into diabetes mellitus group (DM group, =8) and diabetes mellitus + simvastatin group (DM+S group, =8). Rats in DM+S group were treated with simvastatin at the dose of 40 mg/(kg·d)by gavage for 4 weeks, and the other two groups were treated with the same amount of saline. At the end of experiments, the heart tissues were collected for further observation. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in heart tissues were measured by spectrophotometry; HE staining of rat heart slides was used to observe the pathological changes; TUNEL assay was used to determine the apoptosis index of myocardial cells in each groups; The distribution of p53 in the heart tissues was evaluated by immunohistochemistry; Western blot was used to detect the expressions of p53, p53-phospho-serine 15, Bax and Bcl-2 in the heart tissues.@*RESULTS@#①Compared with control group, the content of malondialdehyde (MDA) was increased while the activity of superoxide dismutase (SOD) was decreased significantly in DM group (<0.01). After simvastatin administration, the activity of SOD was increased and the content of MDA was decreased significantly (<0.01). ② HE staining results showed that the myocardial cells in the DM group were disorganized, with unclear morphological structure and a large number of inflammatory cells infiltration. Compared with DM group, the myocardial morphology in DM+S group was improved significantly. ③TUNEL staining results showed that the apoptosis index of myocardial cells in DM group was increased significantly compared with that of control group, and the apoptosis index was decreased significantly after the treatment of simvastatin (<0.01).④ Immunohistochemistry showed that compared with control group,the expression of p53 in DM group was increased significantly, and was expressed in both cytoplasm and nucleus, while the expression of p53 in DM+S group was decreased and the expression of p53 in nucleus was decreased significantly (<0.01). ⑤ The results of Western blot showed that the expression levels of p53, p53-phospho-serine15 and Bax were higher than those in control group, and the expression of Bcl-2 was lower than that in control group (<0.01). After simvastatin administration, the expression levels of p53,p53-phospho-serine 15 (<0.01) and Bax were decreased significantly (<0.05) and the expression of Bcl-2 was increased (<0.05).@*CONCLUSIONS@#Simvastatin exerted protective effects on myocardial injury caused by diabetes through improving the abnormal morphological changes of diabetic myocardium, alleviating oxidative stress and inhibiting apoptosis of myocardial cells. The mechanism is related to the regulation of apoptosis pathway mediated by p53.
Subject(s)
Animals , Rats , Apoptosis , Diabetes Mellitus, Experimental , Myocardium , Oxidative Stress , Rats, Sprague-Dawley , SimvastatinABSTRACT
OBJECTIVE@#To observe the protective effect of simvastatin on renal injury in diabetic rats and to explore the possible molecular mechanism.@*METHODS@#Twenty-four SD rats were randomly divided into normal control (NC) group (=8) and modeling group (=16).The rats in modeling group were injected with streptozotocin intraperitoneally at a dose of 55 mg/kg to establishing diabetic rat model. After diabetic ratmodel established successfully, the diabetic rats were randomly subdivided into diabetes mellitus (DM) group and diabetes mellitus + simvastatin (DM+Sim) group (=8).Rats in DM+Sim group were given simvastatin at a dose of 40 mg/kg by oral gavages, once a day for 4 weeks. Morphological changes and interstitial fibrosis of kidney were observed by histopathological method. The expressions of relative protein in endoplasmic reticulum stress, inflammatory molecules in renal tissues and cells apoptosis were detected by molecular biology method.@*RESULTS@#① Compared with NC group, the pathological changes of glomerulus and tubulointerstitium were obvious, and the collagen fibers were obviously erythrophilous and unevenly distributed in DM group. Compared with DM group, the morphological changes and fibrosis were significantly improved in DM+Sim group. ② The expressions of GRP78, p-IRE1α, NF-κB p65 and MCP-1 in DM group were significantly higher than those in NC group (<0.05), while the expressions of GRP78, p-IRE1α, NF-κB p65 and MCP-1in DM + Sim group were decreased (<0.05). ③ There were a small number of apoptotic nuclei in the glomeruli and adjunctive renal tubules in NC group detected by TUNEL assay, while there were a large number of apoptotic nuclei in DM group (<0.01). The number of apoptotic nuclei was decreased significantly in DM+Sim group (<0.01).@*CONCLUSIONS@#Morphologicalchanges and fibrosis of renal tissue are improved obviously, and the number of apoptotic cells is decreased significantly after administration of simvastatin in diabetic rats. Simvastatin exertsthe protective effect on diabetic nephropathy by inhibiting endoplasmic reticulum stress and NF-κB inflammatory signaling pathway, and reducing renal cell apoptosis.
Subject(s)
Animals , Rats , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Kidney , Rats, Sprague-Dawley , Simvastatin , PharmacologyABSTRACT
The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of HO in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac1 was dependent on the levels of intracellular HO. Puerarin blocked the phosphorylation of extracellular regulated protein kinases (ERK)1/2, abolished activator protein (AP)-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of HO-dependent Rac1 activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregulation of catalase expression and HO-dependent Rac1 activation.
Subject(s)
Animals , Mice , Angiotensin II , Pharmacology , Angiotensin II Type 1 Receptor Blockers , Pharmacology , Animals, Newborn , Catalase , Genetics , Metabolism , Cell Proliferation , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases , Metabolism , Fibroblasts , Gene Expression Regulation , Heart , Hydrogen Peroxide , Metabolism , Pharmacology , Isoflavones , Pharmacology , Myocardium , Cell Biology , Metabolism , NADPH Oxidases , Metabolism , Neuropeptides , Metabolism , Signal Transduction , Transcription Factor AP-1 , Metabolism , Transcriptional Activation , rac1 GTP-Binding Protein , MetabolismABSTRACT
The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of HO in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac1 was dependent on the levels of intracellular HO. Puerarin blocked the phosphorylation of extracellular regulated protein kinases (ERK)1/2, abolished activator protein (AP)-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of HO-dependent Rac1 activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregulation of catalase expression and HO-dependent Rac1 activation.