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Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding of asthma's pathophysiology deepens, a beacon of hope emerges in the form of biological targeted therapies, offering a promising avenue for the management of this challenging condition. These therapies, by precisely inhibiting or modulating pivotal molecules in the inflammatory cascade, offer potential benefits in symptom alleviation, lung function enhancement, and risk reduction of acute exacerbations. They signify a paradigm shift in severe asthma treatment. Within the confines of this article, we embark on a systematic exploration of the immunological underpinnings that define severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.
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INTRODUCTION: The incidence of colorectal cancer is steadily increasing, and the detection of related molecular targets is critical for its diagnosis and treatment. Long noncoding RNA (lncRNA) can play a regulatory role before and after genome transcription, and epigenetic regulation is involved in the process of tumorigenesis and tumor development. METHODS: In this study, qRT-PCR was performed to evaluate the expression of AK093407 in colon cancer and colon para-carcinoma tissues and HCT-15 and HCT-116 cells. SiRNA was transfected into HCT-15 and HCT-116 cells to knock down lncRNA-AK093407. Then, MTT assay was used to test cell proliferation, and flow cytometry was used to test apoptosis and cell cycle. The protein expression of caspase-3, caspase-8, caspase-9, bax, bcl-2, cyclin-A1, cyclin-B1, cyclin-D1, cyclin- E1, p21, p27, and p-Stat3 was determined by Western blot. RESULTS: The results showed that the expression of AK093407 in human colon cancer tissue was higher than in para-carcinoma tissue. The amount of AK093407 in HCT-15 and HCT-116 cells was higher than that in normal colorectal epithelial NM460 cells. When AK093407 was silenced, the proliferation of HCT-15 and HCT-116 cells decreased, the apoptosis rate increased, the cell cycle was arrested in the G1/S phase, the expression of caspase-3, caspase-8, caspase-9, bax, cyclin-A1, cyclin- B1, p21, p27 increased, and the expression of bcl-2, cyclin-D1, cyclin-E1, p-Stat3 decreased. CONCLUSION: These results showed that knockdown of AK093407 could inhibit colon cancer cell proliferation, induce apoptosis and cell cycle arrest, influence the expression of vital factors in mitochondrial apoptosis pathway and cell cycle regulatory pathway, and may negatively regulate JAK/STAT3 through down-regulating p-Stat3.
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Colonic Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Caspase 3 , Caspase 9 , Caspase 8 , Epigenesis, Genetic , bcl-2-Associated X Protein , Colonic Neoplasms/geneticsABSTRACT
ObjectiveTo investigate the effects of 4 weeks of aerobic exercise combined with traditional Chinese medicine （TCM） on the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β） signaling pathway and related apoptotic proteins in AD rats， and to explore its mechanism of action in improving cognitive function of AD rats. MethodFifty male SD rats were randomly divided into Sham group， exercise （EX） group， Alzheimer's disease （AD） group （model）， TCM group （Dabuyuan Jian）， and EX+TCM group， 10 in each group. Aβ25-35 oligomer solution was injected into the hippocampal region to establish the AD rat model， and the EX group underwent 6 days/week of running table training. The TCM group was given Dabuyuan Jian （5.36 g∙kg-1） by gavage， and the EX+TCM group received running table training combined with intragastric administration of Dabuyuan Jian. An equal volume of purified water was given to the Sham， AD， and EX groups by gavage. The rats' learning memory was evaluated by Morris water maze. The morphological changes and ultrastructural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. Western blot was performed to detect the protein expression levels of Akt， p-Akt， GSK-3β， p-GSK-3β， β-catenin， Bcl-2， Bax， and cleaved Caspase-3 in the hippocampus of rats. ResultCompared with the Sham group， the AD group showed an increase in escape latency and total swimming distance， and a decrease in the residence time in the target quadrant （P<0.01）， with loose and disorganized arrangement of hippocampal pyramidal cells， a decrease in density， myelin-like changes in hippocampal ultrastructure， and a blurring of mitochondrial swelling. In addition， the expression of Bcl-2， p-Akt， p-GSK-3β and β-catenin was down-regulated （P<0.05， P<0.01） while the expression of cleaved Caspase-3 was up-regulated （P<0.05）. Compared with the conditions in the AD group， the escape latency and swimming distance were reduced in the EX， TCM， and EX+TCM groups， while the residence time in the target quadrant was increased （P<0.05，P<0.01）， with regularly arranged pyramidal cells， elevated number of cells， and reduced myelin-like changes and improved mitochondrial swelling as seen by transmission electron microscopy. Moreover， the expression of Bcl-2， p-Akt and p-GSK-3β was up-regulated， while the expression of cleaved Caspase-3 was down-regulated（P<0.05，P<0.01）. The EX+TCM group had increased level of β-catenin while the EX and TCM groups were not statistically significant compared with the AD group. Compared with the EX+TCM group， the EX and TCM groups had increased escape latency and swimming distance and decreased residence time in the target quadrant（P<0.05，P<0.01）， with loosely arranged pyramidal cells and reduced synaptic integrity under transmission electron microscopy（P<0.01）. Furthermore， the levels of Bcl-2， p-Akt， p-GSK-3β and β-catenin were lowered （P<0.05，P<0.01）while the level of cleaved Caspase-3 was elevated（P<0.05）. ConclusionAerobic exercise combined with Dabuyuan Jian could improve the cognitive dysfunction of AD rats， and the mechanism might be related to the elevated expression of key proteins in the PI3K/Akt/GSK-3β signaling pathway. The combined use was better than the use of exercise or drugs alone.
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Objective To investigate the effect of FBXW7 on the expression and localization of HSF1 in colorectal cancer cells. Methods The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 deletion (KO) and wild-type (WT) FBXW7-expressing counterpart colorectal cancer cells were detected by Western blot. The nucleoprotein expression and localization of pHSF1Ser326 in heat-shocked or recovery stage cells were observed by Western blot and immunofluorescence method. Results The HSF1 expression level in DLD1 cells transfected with FBXW7α was decreased significantly (P < 0.01). The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 KO cells were higher than those in WT cells (all P < 0.05). HSF1 and pHSF1Ser326 in FBXW7 KO cells were mainly expressed in nucleus and weakly expressed in cytoplasm. After warm stimulation, the expression of HSF1 and pHSF1Ser326 in WT cells recovered to the unstimulated level, while the expression of HSF1 and pHSF1Ser326 in FBXW7 KO cells were higher in the nucleus (all P < 0.01). Conclusion Loss of FBXW7 could affect the nuclear HSF1 recovery after warm stimulation. It may be associated with FBXW7 deletion inhibiting the degradation of nuclear HSF1.
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Objective@#To explore the effects of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) gel on treatment of thefull-thickness frostbite wounds on foot and hand.@*Methods@#From November 2013 to April 2017, a total of 45 patients of 71 full-thickness frostbite wounds on foot and hand meeting the inclusion criteria were admitted to the First Hospital of Jilin University and the prospective randomized controlled study was done. The patients were divided into rhGM-CSF group of 24 patients with 35 wounds and control group of 21 patients with 36 wounds according to the random number table. There were 20 males and 4 females, aged (38±13) years among patients in rhGM-CSF group, and there were 19 males and 2 females, aged (36±14) years among patients in control group. Patients in 2 groups were performed with the same systemic treatment of rewarming, anti-inflammation, pain relief, anti-infection, anti-coagulation, and thrombolysis. Wounds of patients in rhGM-CSF group and control group were respectively treated with rhGM-CSF gel and aloe vera gel for external usage with 10 mg for every square centimeter and dressing change once every 24 hours, until wounds healed completely. The wound inflammatory response was scored on treatment day (TD) 1, 3, 7, 14, wound secretion was collected for bacteria culture and positive bacteria detection rate was calculated before treatment and on TD 6 and 12, adverse drug reaction after drug use was observed, and the complete wound healing time was recorded. Data were processed with Fisher′s exact probability test, analysis of variance for repeated measurement, t test, and Bonferroni correction.@*Results@#The scores of wound inflammatory response of patients in 2 groups on TD 1 and 3 were close (t=0.37, 2.93, P>0.05). The scores of wound inflammatory response of patients on TD 7 and 14 in rhGM-CSF group were significantly higher than those in control group (t=5.77, 5.83, P<0.01). The results of bacteria culture of wound secretion of patients in 2 groups before treatment were negative. The positive bacteria detection rates of wound secretion of patients in rhGM-CSF group on TD 6 and 12 were 5.71% (2/35) and 22.86% (8/35), which were slightly lower than 13.89% (5/36) and 30.56%(11/36) in control group respectively, but there was no significantly statistical difference (P>0.05). No adverse drug response occurred in patients in rhGM-CSF group, while 1 patient in control group had adverse drug response, with symptoms of redness and swelling of wounds and patchy erythema on skin around wounds, which were alleviated by irrigating with normal saline. The complete wound healing time of patients in rhGM-CSF was (12.3±0.5) d, which was significantly shorter than (16.5±0.8) d in control group (t=24.89, P<0.05).@*Conclusions@#The topical rhGM-CSF gel has effects of shortening time of wound healing and reducing inflammatory response of wound on treatment of full-thickness frostbite wounds on foot and hand, which is safe in clinical application.
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Objective To investigate the distribution of the prevalence of albuminuria in elderly population of a community in Tianjin and analyze the situation of their early renal injury and its clinical and environmental risk factors.Methods The morning spot urine sample and the clinical data from 2 050 old population (aged ≥ 60 years)who took part in healthy examination were collected.The concentration of urine albumin and creatinine were tested,and the albumin/creatinine ratio(ACR)was calculated.We analyzed the prevalence of albuminuria,and used logistic regression to analyze the odd ratio(OR) of risk factors.Results In the 2 050 participants,the prevalence was 1162 cases (56.69％) for hypertension,264 cases (12.86％) for diabetes and 568 cases (27.71％) for albuminuria.The prevalence of ACR ＞ 30 mg/g was lower in men than in women (21.61％ vs.32.55％,P＜0.001).The OR for increased ACR was 1.45 in 70-79y subjects as compared with 60-69y subjects,and the OR was 1.89 in ＞80y old people.The OR of increased ACR was 2.03 in ＞80y old people after adjusting gender.Body mass index and waist circumference were not the risk factors of increased ACR after adjusting confounding factors.There was an association between the prevalence of albuminuria and triglycerides(OR=1.19),hypertension(OR=1.68),diabetes(OR=1.95).ACR value was increased along with increased number of cigarettes,however,there was also no association between smoking and albuminuria(P＞ 0.05).Physical activity could reduce the risk of albuminuria,the OR of ACR＞30 mg/g in those undertaking a activity once daily was 0.52 (P =0.027) Conclusions There is a high prevalence of albuminuria in elderly population(higher in female than in male) in a community of Tianjin.Hypertension and diabetes have the greatest influence on ACR.Additionally,the physical activity once daily can reduce the risk of albuminuria.
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In order to screen better flavone prescriptions of anti-Newcastle disease virus (NDV), four flavone ingredients of epimedium flavones (EF), baikal skullcap root flavones (BSRF), wild dendranthema flower flavones (WDFF), and sanchi flavones (SF) screened in previous experiments and their prescriptions were added into chicken embryo fibroblast monolayer with three drug-adding modes respectively. The cellular A(570) values, the highest virus inhibitory rates and the score based on virus inhibitory rate were calculated to compare their antiviral activity. In immune protective test, the effects of three preparations (EF-BSRF, EF-SF-WDFF-BSRF and EF-WDFF-BSRF screened by the results in vitro experiment) on NDV infection were compared in chickens vaccinated with ND vaccine then challenged with NDV. Blood was regularly sampled for serum antibody titer determination. The pathogenic and dead statuses of chickens were clinically examined. The results indicated that the A(570) values of the nine prescriptions, especially the foresaid three prescriptions at almost all concentrations in three drug-adding modes were significantly higher than that of the virus control group. The foresaid three prescriptions presented at the top five of the highest virus inhibitory rate, and located at the highest three of the score rank. The antibody titers and protective rates of the three prescriptions groups were higher than that of VC group, especially EF-SF-WDFF-BSRF group showed significant difference. These results indicated that flavone prescriptions composed with suitable compatibility could possess synergistical action of antiviral effect, ES-SF-WDFF-BSRF prescription could inhibit the cellular infectivity of NDV, improve the protective effect of ND vaccine and would be expected to exploit into a new-type antiviral drug.
