AIM: To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinoma- tosis (PC). METHODS: A retrospective analysis of data was ...AIM: To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinoma- tosis (PC). METHODS: A retrospective analysis of data was performed on consecutive patients who underwent perito-neoscopic and abdominal computed tomography (CT) evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients (36.0%) and 25 patients (33.3%) were diagnosed with TBP and PC, respectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS: Serum c-reactive protein (7.88 ± 6.62 mg/ dL vs 3.12 ± 2.69 mg/dL, P = 0.01), ascites adenosine deaminase (66.76 ± 32.09 IU/L vs 13.89 ± 8.95 IU/L, P < 0.01), ascites lymphocyte proportion (67.77 ± 23.41% vs 48.36 ± 18.78%, P < 0.01), and serumascites albumin gradient (0.72 ± 0.49 g/dL vs 1.05 ± 0.50 g/dL, P = 0.03) were significantly different between the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohydrate antigen 19-9 showed significant difference between two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group (77.8% vs 40.7%) whereas nodular involvement was more common in the PC group (14.8% vs 40.7%, P = 0.04). From receiver operating characteristic (ROC) curves ascites adenosines deaminase (ADA) showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differential diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION: Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differential diagnosis of TBP and PC.展开更多
Objective:To assess the efficacy of ADA isoenzyme estimation over that of total ADA level in pleural fluid and serum as a more efficient diagnostic indicator in tuberculous pleural effusions in high prevalence country...Objective:To assess the efficacy of ADA isoenzyme estimation over that of total ADA level in pleural fluid and serum as a more efficient diagnostic indicator in tuberculous pleural effusions in high prevalence country like India.Methods:The efficacy was analysed in total thirty four patients of pleural effusions.Total ADA was estimated by Guitsi and Galanti Calorimetric method and ADA isoenzymes with and without EHNA[Erythro-9-（2- hydroxy-3-nonyl） adenine]a potent ADA<sub>1</sub> inhibitor using the same method.Results:The results demonstrated a statistically significant values of ADA<sub>2</sub> in serum（P【0.001）,pleural fluid（P = 0.000） and significant value for the ratio of pleural fluid ADA<sub>2</sub>/serum ADA2（P【0.001） and pleural fluid ADA/ADA(<sub>2</sub>（P【0. 005）.The sensitivity and specificity values of pleural fluid ADA|2 is 81.8%and 91.6%（cut off value 60 IU/L for Tuberculous effusions）,serum ADA<sub>2</sub> 95.4%and 66%（cut off value 70 IU/L for tuberculous effusions）. ADA2<sub> </sub>is an isoenzyme,which is significantly raised in tuberculous pleural effusions both in the serum and pleural fluid.Conclusion:Estimation of ADA isoenzymes is redundant as a diagnostic aid over total ADA estimation in view of the limited improvements both in specificity and sensitivity patterns and also in term of cost-benefit ratio.展开更多
AIM To evaluate the relationship between serum adenosine deaminase(ADA) levels and histological features in patients with autoimmune hepatitis(AIH).METHODS A total of 80 subjects(52 AIH cases and 28 healthy controls) ...AIM To evaluate the relationship between serum adenosine deaminase(ADA) levels and histological features in patients with autoimmune hepatitis(AIH).METHODS A total of 80 subjects(52 AIH cases and 28 healthy controls) were included in the study. Patients were diagnosed according to the simplified criteria suggested by the International Autoimmune Hepatitis Group. All of the cases had been diagnosed with AIH between 2010-2015 at Hacettepe University, Department of Gastroenterology. Serum blood samples were collected and stored at-80 ℃ until the biochemical estimation of ADA activity. The diagnosis of patients was confirmed by liver biopsy. Serum ADA > 20 U/L was considered to be high level.RESULTS Mean serum ADA levels were significantly higher in AIH patients than those in healthy controls(25.4 ± 9.6 U/L vs 12.8 ± 2.2 U/L, P < 0.001). Serum ADA levels > 20 U/L were found in 63.5% AIH patients and in 0% healthy controls(P < 0.001). Mean serum ADA levels were significantly increased in each stage of histological activity: 15.2 ± 3.5 U/L for patients with mild interface hepatitis, 23.1 ± 10.0 U/L for patients with moderate interface hepatitis and 30.9 ± 7.0 U/L for patients with severe interface hepatitis(P < 0.001). Correlation analysis showed that there was a positive association between serum ADA levels and histological activity(r = 0.71, P < 0.001). Receiver operating characteristic analysis suggested that 24.5 U/L was the optimum cut-off point of ADA level for severe interface hepatitis(sensitivity 88%, specificity 85.2%, area under thecurve: 0.88).CONCLUSION Because of the positive correlation with inflammatory activity, serum ADA level may be a potential biomarker for predicting or monitoring histological activity in patients with AIH.展开更多
Objective:Relevance of estimation of pleural adenosine deaminase(PADA) and serum adenosine deaminase (SADA) levels in-pleural effusion especially in cases of lymphocytic predominant exudative tubercular effusions. Met...Objective:Relevance of estimation of pleural adenosine deaminase(PADA) and serum adenosine deaminase (SADA) levels in-pleural effusion especially in cases of lymphocytic predominant exudative tubercular effusions. Methods:Fifty patients(33 male and 17 female;age:44.12±11.51 years) with pleural effusions were selected to assay adenosine deaminase(ADA) activity in pleural fluid and serum in adjunct to pleural fluid analysis.Effusions were individually classified as transudates or exudates after careful evaluation of all the biochemical parameters of pleural fluid and serum of patients and on the basis of Lights criteria.Cutoff value for PADA was taken as 60U/L and that for pleural/serum ADA ratio(P/S ADA) was 1.8.Results:Fourty -three patients had exudative effusions among which 38 patients had tuberculous pleural effusions and 5 had nontubercular effusions.7 cases were transudates.Mean PADA levels in tubercular group(78.95±25.32 U/ L) were found to be much higher P=0.0000) than nontubercular(23.00±5.22 U/L) group.SADA levels in tubercular group(31.05±6.42 U/L) were significantly higher(P=0.0000)as compared to nontubercular group(15.58±8.35 U/L).PADA cutoff at 60 U/L yielded sensitivity and.specificity of 81.5%and 100%respectively,whereas P/S ADA ratio at 1.8 gave sensitivity and specificity of 84.2% and 75%respectively. A positive correlation(r=0.507,P= 0.001 1)between PADA and SADA was found in tubercular group but no such correlation(r=0.302,P=0.3407)was observed in nontubercular group.Conclusion: The measurement of ADA in tubercular pleural effusions has not only relevance but also a high diagnostic utility when other clinical and laboratory tests are either negative or confusing.展开更多
Interactions of anionic, cationic and metal phthalocyanine with adenosine deaminase were studied by molecular dynamics and docking simulation. Structural parameters such as solvent accessible surface area (SAS), mid-p...Interactions of anionic, cationic and metal phthalocyanine with adenosine deaminase were studied by molecular dynamics and docking simulation. Structural parameters such as solvent accessible surface area (SAS), mid-point of transition temperature (Tm), radial distribution function (RDF) and hydrogen bond, helix, coil, beta percentage and other physical parameters were obtained. The denaturation of adenosine deaminase (ADA) by heat, anionic and cationic phthalocyanines was compared. A series of 20 ns simulation performed at temperatures ranging from 275 to 450 K, starting from the ADA native structure. Results of radial distribution functions (RDFs) showed that metallic derivative at low concentration behaves the same as osmolytes that increases the beta form and increases the enzyme stability. Molecular docking studies have been carried out to confirm the simulation results. Investigation of binding site and free energy confirmed that the efficiency of interaction with adenosine deaminase depends on metal core. Binding energy of non-metallic form is more negative than metallic form and it significantly decreases for phthalocyanine. Self-aggregation of anionic phthalocyanine decreases in comparison with cationic derivative, therefore enzyme denaturation in the presence of anionic form is higher than the other. Furthermore, thermal stability of the enzyme also depends on temperature in presence of phthalocyanine. Binding site of phthalocyanine on the enzyme has been identified by docking analysis.展开更多
Background: Adenosine deaminase (ADA) and 5'-nucleotidase (5'-NT) play a crucial role in adenosine metabolism in healthy individuals. Adenosine is an inflammatory mediator of asthma. Changes in adenosine metab...Background: Adenosine deaminase (ADA) and 5'-nucleotidase (5'-NT) play a crucial role in adenosine metabolism in healthy individuals. Adenosine is an inflammatory mediator of asthma. Changes in adenosine metabolism and role of ADA and 5'-NT in regulating adenosine level in asthmatics and correlation of these changes with severity of asthma are not clearly understood. Methods: In this study, we screened 5217 patients, of which 2416 were diagnosed with asthma. Further, of 2416 asthmatics, only 45 patients who strictly fulfilled the selection criteria were enrolled in the study. The patients were classified into mild, moderate and severe persistent groups;each group consisted of fifteen patients. Fifteen healthy subjects served as controls. Adenosine levels and activities of 5'-NT, total ADA, ADA1 and ADA2 in serum, lymphocytes and erythrocytes were determined. The data were analysed statistically and p vice versa.展开更多
Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Met...Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Methods We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature.Results Nine patients were identified with two novel mutations(W272X and Q202=).Early-onset infection,thymic abnor-malities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients.The ADA genotype has a major effect on the clinical phenotype.Notably,a novel synonymous mutation(c.606G>A,p.Q202=)was identified in a delayed-onset patient,which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein.Furthermore,the patient showed γδT cells expansion with an increased effect or phenotype,which may be associated with the delayed onset of disease.In addition,we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency.Five patients died with a median age of four months,while two patients received stem cell transplantation and are alive.Conclusions This study described the first case series of Chinese ADA-deficient patients.Early-onset infection,thymic abnormalities and failure to thrive were the most common manifestations in our patients.We identified a synonymous muta-tion that affected pre-mRNA splicing in the ADA gene,which had never been reported in ADA deficiency.Furthermore,we reported cerebral aneurysm in a delayed-onset patient for the first time.Further study is warranted to investigate the underlying mechanisms.展开更多
During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membra...During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.展开更多
A magnetically assisted fluorescence ratiometric technique has been developed for adenosine deaminase assays with high sensitivity using water-soluble cationic conjugated polymers(CCPs).The assay contains three elemen...A magnetically assisted fluorescence ratiometric technique has been developed for adenosine deaminase assays with high sensitivity using water-soluble cationic conjugated polymers(CCPs).The assay contains three elements:a biotin-labeled aptamer of adenosine(biotin-aptamer),a signaling probe single-stranded DNA-tagged fluorescein at terminus(ssDNA-Fl) and a CCP.The specific binding of adenosine to biotin-aptamer makes biotin-aptamer and ssDNA-Fl unhybridized,and the ssDNA-Fl is washed out after streptavidin-coated magnetic beads are added and separated from the assay solution under magnetic field.In this case,after the addition of CCP to the magnetic beads solution,the fluo-rescence resonance energy transfer(FRET) from CCP to fluorescein is inefficient.Upon adding adenosine deaminase,the adenosine is converted into inosine,and the biotin-aptamer is hybridized with ssDNA-Fl to form doubled stranded DNA(biotin-dsDNA-Fl).The ssDNA-Fl is attached to the mag-netic beads at the separation step,and the addition of CCP to the magnetic beads solution leads to efficient FRET from CCP to fluorescein.Thus the adenosine deaminase activity can be monitored by fluorescence spectra in view of the intensity decrease of CCP emission or the increase of fluorescein emission in aqueous solutions.The assay integrates surface-functionalized magnetic particles with significant amplification of detection signal of water-soluble cationic conjugated polymers.展开更多
Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of a...Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.展开更多
Objective To compare the diagnostic performance of interferon gamma releasing assays(T-SPOT.TB)and adenosine deaminase(ADA)in pleural tuberculosis,and therefore to evaluate the value of T-SPOT.TB in a high tuberculosi...Objective To compare the diagnostic performance of interferon gamma releasing assays(T-SPOT.TB)and adenosine deaminase(ADA)in pleural tuberculosis,and therefore to evaluate the value of T-SPOT.TB in a high tuberculosis burden country.Methods From June 2011to November 2012,111 patients with pleural fluid in Beijing Chest Hospital,Capital Medical University展开更多
Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This co...Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.展开更多
BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in ...BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.展开更多
Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was...Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was applied to evaluate the effects of 4 variables by UAPE on cAMP yield.The results showed that the optimal cAMP yield(783.0μg/g)was derived at ratio of liquid to solid 5 mL/g,ratio of pectinase to raw material 1.5%,time 60 min and temperature 40℃.Moreover,the effect of cAMP on the anti-allergic function of action induced by immunoglobulin E(IgE)and its meschanism was investigated through establishing the sensitized cell model in rat basophilic leukemia(RBL-2 H3)cells using dinitrophenylated(DNP)-bovine serum albumin(BSA)-IgE.The results showed that cAMP interfered with sensitized cells,effectively inhibited the occurrence of basophil degranulation in dose dependence,and significantly reduced the activity ofβ-hexosamindase(β-hex),at the optimal concentration of 50μg/mL.The level of anti-inflammatory factor interleukin-10(IL-10)was promoted and the content of pro-inflammatory factor tumor necrosis factor-α(TNF-α)was suppressed by cAMP.In addition,influx of intracellular Ca^(2+) was repressed effectively.Our results demonstrate that jujube cAMP regulated the cytokine balance in the allergy pathway through blocking the influx of extracellular Ca^(2+),with the prevention of allergy symptoms.展开更多
BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brai...BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.展开更多
Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory p...Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.展开更多
文摘AIM: To investigate the usefulness of tumor markers and adenosine deaminase in differentiating between tuberculous peritonitis (TBP) and peritoneal carcinoma- tosis (PC). METHODS: A retrospective analysis of data was performed on consecutive patients who underwent perito-neoscopic and abdominal computed tomography (CT) evaluations. Among 75 patients at the Seoul National University Hospital from January 2000 to June 2010 who underwent both tests, 27 patients (36.0%) and 25 patients (33.3%) were diagnosed with TBP and PC, respectively. Diagnosis was confirmed by peritoneoscopic biopsy. RESULTS: Serum c-reactive protein (7.88 ± 6.62 mg/ dL vs 3.12 ± 2.69 mg/dL, P = 0.01), ascites adenosine deaminase (66.76 ± 32.09 IU/L vs 13.89 ± 8.95 IU/L, P < 0.01), ascites lymphocyte proportion (67.77 ± 23.41% vs 48.36 ± 18.78%, P < 0.01), and serumascites albumin gradient (0.72 ± 0.49 g/dL vs 1.05 ± 0.50 g/dL, P = 0.03) were significantly different between the two groups. Among tumor markers, serum and ascites carcinoembryonic antigen, serum carbohydrate antigen 19-9 showed significant difference between two groups. Abdominal CT examinations showed that smooth involvement of the parietal peritoneum was more common in the TBP group (77.8% vs 40.7%) whereas nodular involvement was more common in the PC group (14.8% vs 40.7%, P = 0.04). From receiver operating characteristic (ROC) curves ascites adenosines deaminase (ADA) showed better discriminative capability than tumor markers. An ADA cut-off level of 21 IU/L was found to yield the best results of differential diagnosis; sensitivity, specificity, positive predictive value, and negative predictive value were 92.0%, 85.0%, 88.5% and 89.5%, respectively. CONCLUSION: Besides clinical and radiologic findings, ascitic fluid ADA measurement is helpful in the differential diagnosis of TBP and PC.
文摘Objective:To assess the efficacy of ADA isoenzyme estimation over that of total ADA level in pleural fluid and serum as a more efficient diagnostic indicator in tuberculous pleural effusions in high prevalence country like India.Methods:The efficacy was analysed in total thirty four patients of pleural effusions.Total ADA was estimated by Guitsi and Galanti Calorimetric method and ADA isoenzymes with and without EHNA[Erythro-9-（2- hydroxy-3-nonyl） adenine]a potent ADA<sub>1</sub> inhibitor using the same method.Results:The results demonstrated a statistically significant values of ADA<sub>2</sub> in serum（P【0.001）,pleural fluid（P = 0.000） and significant value for the ratio of pleural fluid ADA<sub>2</sub>/serum ADA2（P【0.001） and pleural fluid ADA/ADA(<sub>2</sub>（P【0. 005）.The sensitivity and specificity values of pleural fluid ADA|2 is 81.8%and 91.6%（cut off value 60 IU/L for Tuberculous effusions）,serum ADA<sub>2</sub> 95.4%and 66%（cut off value 70 IU/L for tuberculous effusions）. ADA2<sub> </sub>is an isoenzyme,which is significantly raised in tuberculous pleural effusions both in the serum and pleural fluid.Conclusion:Estimation of ADA isoenzymes is redundant as a diagnostic aid over total ADA estimation in view of the limited improvements both in specificity and sensitivity patterns and also in term of cost-benefit ratio.
文摘AIM To evaluate the relationship between serum adenosine deaminase(ADA) levels and histological features in patients with autoimmune hepatitis(AIH).METHODS A total of 80 subjects(52 AIH cases and 28 healthy controls) were included in the study. Patients were diagnosed according to the simplified criteria suggested by the International Autoimmune Hepatitis Group. All of the cases had been diagnosed with AIH between 2010-2015 at Hacettepe University, Department of Gastroenterology. Serum blood samples were collected and stored at-80 ℃ until the biochemical estimation of ADA activity. The diagnosis of patients was confirmed by liver biopsy. Serum ADA > 20 U/L was considered to be high level.RESULTS Mean serum ADA levels were significantly higher in AIH patients than those in healthy controls(25.4 ± 9.6 U/L vs 12.8 ± 2.2 U/L, P < 0.001). Serum ADA levels > 20 U/L were found in 63.5% AIH patients and in 0% healthy controls(P < 0.001). Mean serum ADA levels were significantly increased in each stage of histological activity: 15.2 ± 3.5 U/L for patients with mild interface hepatitis, 23.1 ± 10.0 U/L for patients with moderate interface hepatitis and 30.9 ± 7.0 U/L for patients with severe interface hepatitis(P < 0.001). Correlation analysis showed that there was a positive association between serum ADA levels and histological activity(r = 0.71, P < 0.001). Receiver operating characteristic analysis suggested that 24.5 U/L was the optimum cut-off point of ADA level for severe interface hepatitis(sensitivity 88%, specificity 85.2%, area under thecurve: 0.88).CONCLUSION Because of the positive correlation with inflammatory activity, serum ADA level may be a potential biomarker for predicting or monitoring histological activity in patients with AIH.
文摘Objective:Relevance of estimation of pleural adenosine deaminase(PADA) and serum adenosine deaminase (SADA) levels in-pleural effusion especially in cases of lymphocytic predominant exudative tubercular effusions. Methods:Fifty patients(33 male and 17 female;age:44.12±11.51 years) with pleural effusions were selected to assay adenosine deaminase(ADA) activity in pleural fluid and serum in adjunct to pleural fluid analysis.Effusions were individually classified as transudates or exudates after careful evaluation of all the biochemical parameters of pleural fluid and serum of patients and on the basis of Lights criteria.Cutoff value for PADA was taken as 60U/L and that for pleural/serum ADA ratio(P/S ADA) was 1.8.Results:Fourty -three patients had exudative effusions among which 38 patients had tuberculous pleural effusions and 5 had nontubercular effusions.7 cases were transudates.Mean PADA levels in tubercular group(78.95±25.32 U/ L) were found to be much higher P=0.0000) than nontubercular(23.00±5.22 U/L) group.SADA levels in tubercular group(31.05±6.42 U/L) were significantly higher(P=0.0000)as compared to nontubercular group(15.58±8.35 U/L).PADA cutoff at 60 U/L yielded sensitivity and.specificity of 81.5%and 100%respectively,whereas P/S ADA ratio at 1.8 gave sensitivity and specificity of 84.2% and 75%respectively. A positive correlation(r=0.507,P= 0.001 1)between PADA and SADA was found in tubercular group but no such correlation(r=0.302,P=0.3407)was observed in nontubercular group.Conclusion: The measurement of ADA in tubercular pleural effusions has not only relevance but also a high diagnostic utility when other clinical and laboratory tests are either negative or confusing.
文摘Interactions of anionic, cationic and metal phthalocyanine with adenosine deaminase were studied by molecular dynamics and docking simulation. Structural parameters such as solvent accessible surface area (SAS), mid-point of transition temperature (Tm), radial distribution function (RDF) and hydrogen bond, helix, coil, beta percentage and other physical parameters were obtained. The denaturation of adenosine deaminase (ADA) by heat, anionic and cationic phthalocyanines was compared. A series of 20 ns simulation performed at temperatures ranging from 275 to 450 K, starting from the ADA native structure. Results of radial distribution functions (RDFs) showed that metallic derivative at low concentration behaves the same as osmolytes that increases the beta form and increases the enzyme stability. Molecular docking studies have been carried out to confirm the simulation results. Investigation of binding site and free energy confirmed that the efficiency of interaction with adenosine deaminase depends on metal core. Binding energy of non-metallic form is more negative than metallic form and it significantly decreases for phthalocyanine. Self-aggregation of anionic phthalocyanine decreases in comparison with cationic derivative, therefore enzyme denaturation in the presence of anionic form is higher than the other. Furthermore, thermal stability of the enzyme also depends on temperature in presence of phthalocyanine. Binding site of phthalocyanine on the enzyme has been identified by docking analysis.
文摘Background: Adenosine deaminase (ADA) and 5'-nucleotidase (5'-NT) play a crucial role in adenosine metabolism in healthy individuals. Adenosine is an inflammatory mediator of asthma. Changes in adenosine metabolism and role of ADA and 5'-NT in regulating adenosine level in asthmatics and correlation of these changes with severity of asthma are not clearly understood. Methods: In this study, we screened 5217 patients, of which 2416 were diagnosed with asthma. Further, of 2416 asthmatics, only 45 patients who strictly fulfilled the selection criteria were enrolled in the study. The patients were classified into mild, moderate and severe persistent groups;each group consisted of fifteen patients. Fifteen healthy subjects served as controls. Adenosine levels and activities of 5'-NT, total ADA, ADA1 and ADA2 in serum, lymphocytes and erythrocytes were determined. The data were analysed statistically and p vice versa.
基金the National Natural Science Foundation of China(81971547 and 81900136)Beijing Hospitals Authority's Ascent Plan(DFL20221001)+1 种基金National Key Research and Development Program of China(2021YFC2702005)Wu Jieping Medical Foundation(320.6750.2022-03-53).
文摘Background Adenosine deaminase(ADA)is a key enzyme in the purine salvage pathway.Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency.To date,few Chinese cases have been reported.Methods We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature.Results Nine patients were identified with two novel mutations(W272X and Q202=).Early-onset infection,thymic abnor-malities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients.The ADA genotype has a major effect on the clinical phenotype.Notably,a novel synonymous mutation(c.606G>A,p.Q202=)was identified in a delayed-onset patient,which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein.Furthermore,the patient showed γδT cells expansion with an increased effect or phenotype,which may be associated with the delayed onset of disease.In addition,we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency.Five patients died with a median age of four months,while two patients received stem cell transplantation and are alive.Conclusions This study described the first case series of Chinese ADA-deficient patients.Early-onset infection,thymic abnormalities and failure to thrive were the most common manifestations in our patients.We identified a synonymous muta-tion that affected pre-mRNA splicing in the ADA gene,which had never been reported in ADA deficiency.Furthermore,we reported cerebral aneurysm in a delayed-onset patient for the first time.Further study is warranted to investigate the underlying mechanisms.
基金supported by University of Florence RICATEN 2023 to EC.Grant/Award Numbers 58514_InternazionalizzazioneUniversity of Florence,to EC.Parkinson’s UK,Grant/Award Number:H-0902 to AJGWellcome Trust,Grant/Award Number:0926/Z/10/Z to AJG。
文摘During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.
基金This study was supported by grants from the National Natural Science Foundation of China，Natural Science Foundation of Guangxi Zhuang Autonomous Region (No.0728137).The authors have declared that no conflict of interest exists
基金Supported by the "100 Talents" Program of the Chinese Academy of Sciencesthe National Natural Science Foundation of China (Grant No.20574073)
文摘A magnetically assisted fluorescence ratiometric technique has been developed for adenosine deaminase assays with high sensitivity using water-soluble cationic conjugated polymers(CCPs).The assay contains three elements:a biotin-labeled aptamer of adenosine(biotin-aptamer),a signaling probe single-stranded DNA-tagged fluorescein at terminus(ssDNA-Fl) and a CCP.The specific binding of adenosine to biotin-aptamer makes biotin-aptamer and ssDNA-Fl unhybridized,and the ssDNA-Fl is washed out after streptavidin-coated magnetic beads are added and separated from the assay solution under magnetic field.In this case,after the addition of CCP to the magnetic beads solution,the fluo-rescence resonance energy transfer(FRET) from CCP to fluorescein is inefficient.Upon adding adenosine deaminase,the adenosine is converted into inosine,and the biotin-aptamer is hybridized with ssDNA-Fl to form doubled stranded DNA(biotin-dsDNA-Fl).The ssDNA-Fl is attached to the mag-netic beads at the separation step,and the addition of CCP to the magnetic beads solution leads to efficient FRET from CCP to fluorescein.Thus the adenosine deaminase activity can be monitored by fluorescence spectra in view of the intensity decrease of CCP emission or the increase of fluorescein emission in aqueous solutions.The assay integrates surface-functionalized magnetic particles with significant amplification of detection signal of water-soluble cationic conjugated polymers.
基金supported by the Natural Nature Science Foundation of China,Nos.82030071,81874004the Science and Technology Major Project of Changsha,No.kh2103008(all to JZH).
文摘Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury.However,its effect on spinal cord injury in aged mice remains unclear.Considering the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord injury.In this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen method.We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord.Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro.Furthermore,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological function.The role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury.These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.
文摘Objective To compare the diagnostic performance of interferon gamma releasing assays(T-SPOT.TB)and adenosine deaminase(ADA)in pleural tuberculosis,and therefore to evaluate the value of T-SPOT.TB in a high tuberculosis burden country.Methods From June 2011to November 2012,111 patients with pleural fluid in Beijing Chest Hospital,Capital Medical University
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+4 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005.
文摘Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.
基金Supported by National Natural Science Foundation of China,No.81160057,No.81860102,and No.82060102Natural Science Foundation of Hainan Province,High-level Personnel Program,No.821RC1116+1 种基金Research Project of Health Industry in Hainan Province,No.20A200066Hainan Provincial Clinical Medical Center.
文摘BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.
基金supported by grant from the National Key Research and Development Program of China(2018YFC1602201)the Open Research Fund Program of Beijing Key Lab of Plant Resource Research and Development,Beijing Technology and Business University(PRRD-2021-YB8)+1 种基金the National Natural Science Fund(31601395)the Key Program for Shaanxi Science and Technology(2020NY-146)。
文摘Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was applied to evaluate the effects of 4 variables by UAPE on cAMP yield.The results showed that the optimal cAMP yield(783.0μg/g)was derived at ratio of liquid to solid 5 mL/g,ratio of pectinase to raw material 1.5%,time 60 min and temperature 40℃.Moreover,the effect of cAMP on the anti-allergic function of action induced by immunoglobulin E(IgE)and its meschanism was investigated through establishing the sensitized cell model in rat basophilic leukemia(RBL-2 H3)cells using dinitrophenylated(DNP)-bovine serum albumin(BSA)-IgE.The results showed that cAMP interfered with sensitized cells,effectively inhibited the occurrence of basophil degranulation in dose dependence,and significantly reduced the activity ofβ-hexosamindase(β-hex),at the optimal concentration of 50μg/mL.The level of anti-inflammatory factor interleukin-10(IL-10)was promoted and the content of pro-inflammatory factor tumor necrosis factor-α(TNF-α)was suppressed by cAMP.In addition,influx of intracellular Ca^(2+) was repressed effectively.Our results demonstrate that jujube cAMP regulated the cytokine balance in the allergy pathway through blocking the influx of extracellular Ca^(2+),with the prevention of allergy symptoms.
基金Supported by Chongqing Key Diseases Research and Application Demonstration Program,No.2019ZX003General Project of Chongqing Nature Science Foundation,No.cstc2021jcyj-msxmX0283.
文摘BACKGROUND Dopamine and cyclic adenosine monophosphate(cAMP)-regulated phosphop-rotein with an apparent Mr of 32000(DARPP-32)is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain.However,recent studies have shown that DARPP-32 is also expressed in other tissues,including colorectal cancer(CRC),where its function is not well understood.AIM To explore the effect of DARPP-32 on CRC progression.METHODS The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays.The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine assays,while apoptosis was measured by flow cytometry.The migratory and invasive potential of CRC cell lines were deter-mined using wound healing and transwell chamber assays.In vivo studies involved monitoring the growth rate of xenograft tumors.Finally,the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses.RESULTS DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC.Overexpression of DARPP-32 was shown to promote cancer cell proliferation,migration,and invasion and reduce apoptosis.DARPP-32 knockdown resulted in the opposite functional effects.Mechanistically,DARPP-32 may regulate the phosphoinositide 3-kinase(PI3K)/AKT signaling pathway in order to carry out its biological function.CONCLUSION DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.
基金supported by the National Natural Science Foundation of ChinaNos.81971047 (to WTL) and 82073910 (to XFW)+2 种基金the Natural Science Foundation of Jiangsu Province,No.BK20191253 (to XFW)Key R&D Program (Social Development) Project of Jiangsu Province,No.BE2019 732 (to WTL)Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University) Clinical Capacity Enhancement Project,No.JSPH-511B2018-8 (to YBP)。
文摘Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance.
