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1.
Neurourol Urodyn ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979850

ABSTRACT

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

2.
J Asian Nat Prod Res ; 26(2): 248-258, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37905564

ABSTRACT

Four new alkaloids (1 - 4), together with five known ones (5 - 9), were isolated from the bulbs of Dactylicapnos scandens. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolates were tested for their ability to modulate neuronal Ca2+ mobilization in primary cultured neocortical neurons. Compound 8 inhibited spontaneous Ca2+ oscillations at low micromolar concentrations.


Subject(s)
Alkaloids , Alkaloids/chemistry , Plant Roots/chemistry , Neurons
3.
Zhonghua Nan Ke Xue ; 29(7): 579-286, 2023 Jul.
Article in Zh | MEDLINE | ID: mdl-38619403

ABSTRACT

OBJECTIVE: To explore the relationship between CRYAB and the prognosis of prostate cancer (PCa) as well as the potential mechanism. METHODS: Bioinformatics analysis was performed using R software, including differential gene expression and clinical correlation analysis, receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve generation. Gene expression was detected using RT-qPCR, and protein expression was validated using Western Blot. The proliferation, apoptosis, and metastatic ability of PCa cells were detected using CCK8, TUNEL, Transwell migration, and invasion assays. RESULTS: According to the TCGA and GEO databases, CRYAB mRNA expression was down-regulated in PCa tissue compared with normal tissue (P< 0.05), and CRYAB mRNA and protein were down-regulated in PCa cells compared with RWPE1 cells (P< 0.05). Cell function experiments showed that up-regulated CRYAB could inhibit the proliferation, invasion, and migration of prostate cancer cells, promote apoptosis (P< 0.05), and up-regulate CDH1 expression while down-regulating CDH2 expression in the CRYAB-upregulated cell line. In addition, CRYAB mRNA expression was correlated with Gleason score (P< 0.01). The area under the ROC curve was 0.914, the KM curve showed that CRYAB had prognostic value for progression-free survival (P = 0.008) and disease-specific survival (P = 0.032). CONCLUSION: CRYAB is down-regulated in PCa tissue and is associated with the anti- tumor function of PCa cells. It may affect the metastatic ability of prostate cancer cells by regulating epithelial-mesenchymal transition molecules. CRYAB mRNA has important diagnostic and prognostic value in PCa.


Subject(s)
Prostatic Neoplasms , Male , Humans , Prostate , Apoptosis , Blotting, Western , RNA, Messenger , alpha-Crystallin B Chain
4.
Paediatr Perinat Epidemiol ; 36(3): 390-398, 2022 05.
Article in English | MEDLINE | ID: mdl-34431114

ABSTRACT

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.


Subject(s)
Pneumothorax , Respiratory Distress Syndrome, Newborn , Continuous Positive Airway Pressure/adverse effects , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Pneumothorax/etiology , Pregnancy , Respiratory Distress Syndrome, Newborn/complications , Respiratory Distress Syndrome, Newborn/epidemiology , Respiratory Distress Syndrome, Newborn/therapy , Retrospective Studies
5.
J Nat Prod ; 85(3): 599-606, 2022 03 25.
Article in English | MEDLINE | ID: mdl-34957832

ABSTRACT

Nine new cadinane sesquiterpenoids, alanenses A-I (1-9), were isolated from the leaves of Alangium chinense together with three previously reported analogues (10-12). The structures of these molecules were elucidated by interpretation of spectroscopic and spectrometric data. Absolute configurations were established by the comparison of experimental and calculated ECD data, chemical degradation studies for sugar moieties, and a single-crystal X-ray diffraction analysis. Compounds 1 and 2 were isolated as racemates, and enantiopurification was achieved by chiral HPLC. Compounds 3-5 are glycosylated cadinanes bearing a ß-d-glucose unit, while compounds 6-9 incorporate a hydroxymethyl group in either the free form or additional ring fusion. The structure of compound 11 was originally misassigned and later revised using additional NMR data. The corrected structure is here supported by X-ray single-crystal analysis. Compounds 1 and 2 inhibit spontaneous calcium channel oscillations at low micromolar concentrations.


Subject(s)
Alangiaceae , Sesquiterpenes , Alangiaceae/chemistry , Calcium Signaling , Glycosides/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Polycyclic Sesquiterpenes , Sesquiterpenes/chemistry
6.
J Nat Prod ; 85(4): 1157-1166, 2022 04 22.
Article in English | MEDLINE | ID: mdl-35385291

ABSTRACT

Thirteen new benzamide alkaloids, delphiniumines A-M (1-13), together with one known analogue (14), were isolated from Delphinium anthriscifolium Hance. All of the structures were determined by spectroscopic and spectrometric analyses. Absolute configuration for 1 was established using experimental and calculated ECD data, as well as by X-ray crystallography analysis. Compound 1 possesses a previously undescribed polysubstituted cyclopentene carbon framework. Compound 2 was isolated as an artifact from 1 during the extraction process. Compound 7 is glycosylated with a ß-D-glucose unit. Compound 13 bears a chlorine substituent. At a concentration of 10 µM, compounds 6, 8, and 10-12 suppressed LPS-induced NO production in RAW264.7 cells with inhibition rates ranging from 40.3% to 78.8%.


Subject(s)
Alkaloids , Delphinium , Diterpenes , Alkaloids/chemistry , Benzamides , Cyclopentanes/pharmacology , Delphinium/chemistry , Diterpenes/chemistry , Molecular Structure
7.
Molecules ; 27(4)2022 Feb 15.
Article in English | MEDLINE | ID: mdl-35209101

ABSTRACT

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.


Subject(s)
Chrysobalanaceae/chemistry , Phytochemicals/analysis , Phytochemicals/chemistry , Chemical Fractionation , Gas Chromatography-Mass Spectrometry , Humans , Molecular Structure , Phytochemicals/isolation & purification , Plant Extracts/analysis , Plant Extracts/chemistry , Plant Extracts/isolation & purification
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 994-1000, 2022.
Article in Zh | MEDLINE | ID: mdl-36111717

ABSTRACT

OBJECTIVES: To study the changes in the mortality rate and cause of death of hospitalized neonates in grade A tertiary hospitals in Weifang City of Shandong Province during a 10-year period. METHODS: A retrospective analysis was performed on 461 neonates who died in three grade A tertiary hospitals in Weifang City of Shandong Province from January 1, 2012 to December 31, 2021. The related clinical data were collected to examine the changes of neonatal mortality with time, gestational age (GA) and birth weight (BW). The main causes of death of the neonates were compared between the first 5 years (2012-2016) and the last 5 years (2017-2021) in the period. RESULTS: A total of 43 037 neonates were admitted from 2012 to 2021, among whom 461 died, resulting in a mortality rate of 1.07%. The mortality rate in the last 5 years was significantly lower than that in the first 5 years [0.96% (211/22 059 vs 1.19% (250/20 978); P<0.05]. The mortality rate of neonates decreased with the increases in GA and BW (P<0.05). In the first 5 years, the top three main causes of neonatal death were respiratory distress syndrome (RDS), sepsis, and pneumorrhagia, while in the last 5 years, the top three causes were sepsis, pneumorrhagia, and RDS. The leading cause of death was severe asphyxia for the neonates with a GA of <26 weeks and a BW of <750 g in both the first and last 5 years. For the neonates with a GA of 26-<28 weeks, the leading cause of death changed from RDS in the first 5 years to pneumorrhagia in the last 5 years. For the neonates with a BW of 750-<1 000 g, the leading cause of death changed from pneumorrhagia in the first 5 years to RDS in the last 5 years. For the neonates with a GA of 28-<32 weeks and a BW of 1 000-<1 500 g, the leading cause of death was RDS in both the first and last 5 years. For the neonates with a GA of 32-<37 weeks and a BW of 1 500-<2 500 g, the leading cause of death changed from RDS in the first 5 years to sepsis in the last 5 years. The leading cause of death was sepsis for the neonates with a GA of 37-<42 weeks and a BW of 2 500-<4 000 g in both the first and last 5 years. CONCLUSIONS: The mortality rate of neonates in the grade A tertiary hospitals in Weifang City of Shandong Province has been decreasing in the past 10 years, and it decreases with the increases in GA and BW. Sepsis, RDS, and pneumorrhagia are the leading causes of neonatal death. The mortality rate caused by RDS decreases from the first 5 years to the last 5 years, while the mortality rate caused by sepsis or pneumorrhagia increases from the first 5 years to the last 5 years. Therefore, reducing the incidence rates of sepsis, RDS, and pneumorrhagia is the key to reducing neonatal mortality.


Subject(s)
Perinatal Death , Respiratory Distress Syndrome, Newborn , Sepsis , Birth Weight , Cause of Death , Female , Humans , Infant, Newborn , Retrospective Studies
9.
Bioorg Chem ; 99: 103795, 2020 06.
Article in English | MEDLINE | ID: mdl-32240871

ABSTRACT

Eight new alkaloids, including five isoquinoline alkaloids, a benzoazepine alkaloid, two isoindole alkaloids, and three synthetic alkaloids firstly obtained from the natural sources, together with three known ones were isolated from the bulbs of Corydalis decumbens. The structures were determined by analysis of their spectroscopic data and single-crystal X-ray diffraction. This is the first report of isoindole alkaloid and benzoazepine alkaloid from the genus Corydalis. Full NMR data for 9-11 are reported here for the first time. Moreover, the ability to modulate neuronal Ca2+ mobilization of the isolated alkaloids was tested in primary cultured neocortical neurons. Compound 7 inhibited spontaneous Ca2+ oscillations in primary neocortical neuron cultures at low micromolar concentrations.


Subject(s)
Alkaloids/pharmacology , Biological Products/pharmacology , Corydalis/chemistry , Neurons/drug effects , Alkaloids/chemistry , Alkaloids/isolation & purification , Animals , Biological Products/chemistry , Biological Products/isolation & purification , Calcium/metabolism , Crystallography, X-Ray , Dose-Response Relationship, Drug , Mice , Mice, Inbred C57BL , Models, Molecular , Molecular Structure , Neurons/metabolism , Structure-Activity Relationship
10.
Microb Pathog ; 131: 254-258, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30999020

ABSTRACT

BACKGROUND: Canine distemper virus (CDV) can cause a highly contagious disease to canid. However, how CDV affects peripheral blood lymphocyte (PBL) remains unclear. METHODS: In this study, CDV infected PBL was cultured to investigate the effect of CDV on the differentiation of lymphocytes and the mRNA expression of inflammatory cytokines in PBL. RESULTS: The results showed that CDV changed the phenotype of lymphocytes and increased the percentage of CD4+CD8+ T cells. To explore the effect of immune response of lymphocytes to CDV, the mRNA expression of pro- and anti-inflammatory cytokines was examined. Interleukin (IL-6, IL-12B), and tumor necrosis factor (TNF)-α mRNA expression was significantly increased at 12-48 h after CDV infection. IL-10 mRNA expression was dramatically enhanced at 12-36 h after CDV infection. However, IL-4 and transforming growth factor (TGF-ß) were not response to CDV infection. These results indicated that PBL differentiated intoCD4+CD8+ T cells and improved the inflammatory response to CDV infection. CONCLUSIONS: After CDV infection, PBL differentiated into CD4+CD8+ T cells and initiated inflammatory response.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Differentiation , Cytokines/metabolism , Distemper Virus, Canine/pathogenicity , Distemper/immunology , Lymphocytes/metabolism , RNA, Messenger/metabolism , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Distemper/virology , Dogs , Female , Interleukin-10/metabolism , Lymphocytes/immunology , Phenotype , Transforming Growth Factor beta/metabolism
11.
Neuroendocrinology ; 109(4): 322-332, 2019.
Article in English | MEDLINE | ID: mdl-30904918

ABSTRACT

BACKGROUND/AIMS: Glucocorticoids are essential in modulating memory processes of emotionally arousing experiences and we have shown that corticosteroid-binding globulin (CBG) influences glucocorticoid delivery to the brain. Here, we investigated the role of CBG in contextual and recognition long-term memory according to stress intensity. METHOD: We used adult male mice totally deficient in CBG (Cbg KO) or brain-specific Cbg KO (CbgCamk KO) to examine their performance in contextual fear conditioning (CFC) and au-ditory fear conditioning, both at short (1 h) and long-term (24 h). Long-term memory in Cbg KO was further analyzed in conditioned odor aversion and in novel object recognition task (NORT) with different paradigms, that is, with and without prior habituation to the context, with a mild or strong stressor applied during consolidation. In the NORT experiments, total and free glucocorticoid levels were measured during consolidation. RESULTS: Impaired memory was observed in the Cbg KO but not in the CbgCamk KO in the CFC and the NORT without habituation when tested 24 h later. However, Cbg KO displayed normal behavior in the NORT with previous habituation and in the NORT with a mild stressor. In condition of the NORT with a strong stressor, Cbg KO retained good 24 h memory performance while controls were impaired. Total and free glucocorticoids levels were always higher in controls than in Cbg KO except in NORT with mild stressor where free glucocorticoids were equivalent to controls. CONCLUSIONS: These data indicate that circulating but not brain CBG influences contextual and recognition long-term memory in relation with glucocorticoid levels.


Subject(s)
Fatigue/psychology , Genetic Diseases, Inborn/psychology , Memory Consolidation , Recognition, Psychology/physiology , Transcortin/deficiency , Acoustic Stimulation , Animals , Fear , Glucocorticoids/metabolism , Male , Memory Disorders/genetics , Memory Disorders/psychology , Memory, Long-Term , Mice , Mice, Knockout , Odorants , Stress, Psychological/psychology
12.
J Nat Prod ; 82(10): 2713-2720, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31599578

ABSTRACT

The new phthalideisoquinoline hemiacetal alkaloids (2-7) and the known analogues (1 and 8) were isolated from the bulbs of Corydalis decumbens. The new compounds were characterized by analysis of their NMR spectroscopic data, chemical degradation syntheses, X-ray crystallography, and comparison of experimental and calculated ECD data. All the isolates were screened in vitro for inhibitory activity of spontaneous calcium oscillations in primary cultured neocortical neurons. Compounds 1-3 and 5-7 were found to be active in the suppression of spontaneous calcium oscillations with IC50 values of 6.8, 5.6, 11.6, 10.2, 8.3, and 3.1 µM, respectively. It was also observed that the presence of hydroxy, methoxy, and ethoxy groups at the remote stereogenic center C-7' of some isolated phthalideisoquinoline hemiacetal alkaloids could alter the preferred conformation and invert the sign of optical rotation, rather than this resulting from configurational isomerism at C-1 or C-9, and that the 3J1,9 coupling constants of these analogues varied accordingly. For example, compounds 1 and 6 are levorotatory, despite these molecules having the same carbon skeleton and absolute configuration as (+)-egenine. This emphasizes the potential risk of incorrectly assigning absolute configuration based only on observed coupling constants or optical rotation when comparing the data of new compounds with literature values for known analogues, especially within this class of molecules.


Subject(s)
Benzylisoquinolines/isolation & purification , Calcium Signaling/drug effects , Corydalis/chemistry , Benzylisoquinolines/chemistry , Benzylisoquinolines/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation
13.
Anim Biotechnol ; 30(1): 7-12, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29527980

ABSTRACT

The α-adducin (ADD1) is a subunit of adducin which is a cytoskeleton heterodimeric protein. Adducin participates in oocytes chromosome meiosis of mice, prompting adducin has an effect on embryonic development. Adducin gene mutation has significantly functional change. So the present study was to identify and characterize polymorphisms within the coding region of the bovine ADD1 gene among different cattle breeds. Here, 11 novel single nucleotide polymorphisms (SNPs 1-11) were identified by DNA sequencing and polymerase chain reaction-single stranded conformational polymorphism, there were one synonymous mutation in exon 1 (SNP1); four missense mutations in exons 4, 7, and 8 (SNPs 3-6); and six mutations in introns 4, 12, 13, and 14 (SNPs 2, 7-10). The statistical analyses indicated that the some SNPs are associated with the growth traits (body length, body height, chest circumference, and hucklebone width) in Chinese Jiaxian cattle population. Our results provide evidence that polymorphisms in the ADD1 gene are associated with growth traits, and may be used for marker-assisted selection in beef cattle breeding program.


Subject(s)
Calmodulin-Binding Proteins/genetics , Cattle/genetics , Genetic Variation , Animals , Body Size/genetics , Cattle/growth & development , Exons/genetics , Phenotype , Polymorphism, Single Nucleotide/genetics
14.
J Neurosci ; 37(46): 11114-11126, 2017 11 15.
Article in English | MEDLINE | ID: mdl-29030432

ABSTRACT

Classical and systems genetics have identified wide networks of genes associated with cognitive and neurodevelopmental diseases. In parallel to deciphering the role of each of these genes in neuronal or synaptic function, evaluating the response of neuronal and molecular networks to gene loss of function could reveal some pathophysiological mechanisms potentially accessible to nongenetic therapies. Loss of function of the Rho-GAP oligophrenin-1 is associated with cognitive impairments in both human and mouse. Upregulation of both PKA and ROCK has been reported in Ophn1-/y mice, but it remains unclear whether kinase hyperactivity contributes to the behavioral phenotypes. In this study, we thoroughly characterized a prominent perseveration phenotype displayed by Ophn1-deficient mice using a Y-maze spatial working memory (SWM) test. We report that Ophn1 deficiency in the mouse generated severe cognitive impairments, characterized by both a high occurrence of perseverative behaviors and a lack of deliberation during the SWM test. In vivo and in vitro pharmacological experiments suggest that PKA dysregulation in the mPFC underlies cognitive dysfunction in Ophn1-deficient mice, as assessed using a delayed spatial alternation task results. Functionally, mPFC neuronal networks appeared to be affected in a PKA-dependent manner, whereas hippocampal-PFC projections involved in SWM were not affected in Ophn1-/y mice. Thus, we propose that discrete gene mutations in intellectual disability might generate "secondary" pathophysiological mechanisms, which are prone to become pharmacological targets for curative strategies in adult patients.SIGNIFICANCE STATEMENT Here we report that Ophn1 deficiency generates severe impairments in performance at spatial working memory tests, characterized by a high occurrence of perseverative behaviors and a lack of decision making. This cognitive deficit is consecutive to PKA deregulation in the mPFC that prevents Ophn1 KO mice to exploit a correctly acquired rule. Functionally, mPFC neuronal networks appear to be affected in a PKA-dependent manner, whereas behaviorally important hippocampal projections were preserved by the mutation. Thus, we propose that discrete gene mutations in intellectual disability can generate "secondary" pathophysiological mechanisms prone to become pharmacological targets for curative strategies in adults.


Subject(s)
Cyclic AMP-Dependent Protein Kinases/metabolism , Cytoskeletal Proteins/deficiency , GTPase-Activating Proteins/deficiency , Memory Disorders/metabolism , Memory, Short-Term/physiology , Nuclear Proteins/deficiency , Prefrontal Cortex/metabolism , Animals , Male , Maze Learning/physiology , Memory Disorders/physiopathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Net/metabolism , Nerve Net/physiopathology , Organ Culture Techniques , Prefrontal Cortex/physiopathology , Random Allocation
16.
Zhongguo Zhong Yao Za Zhi ; 43(3): 596-602, 2018 Feb.
Article in Zh | MEDLINE | ID: mdl-29600628

ABSTRACT

To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS), the male SD rats were intraperitoneally injected with streptozotocin(STZ, 60 mg·kg⁻¹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR), the low-dose Nar group(Nar25), the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25, Nar50, Nar100 groups were orally administered with Nar at the doses of 25.0, 50.0, 100.0 mg·kg⁻¹ per day, respectively, while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatment, fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the results, compared with control group, the myocardial structure was damaged, the content of MDA was increased, while the activities of SOD were decreased(P<0.05) in T1DR group. GRP78, CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(P<0.05, P<0.01). Compared with T1DR group, myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased, while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased, especially in middle and high-dose groups(P<0.05, P<0.01). After treatment with Nar for 8 weeks, myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreased, while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78, CHOP and caspase 12 were increased, especially in middle and high-dose groups(P<0.05, P<0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.


Subject(s)
Cardiotonic Agents/pharmacology , Diabetic Cardiomyopathies/drug therapy , Endoplasmic Reticulum Stress/drug effects , Flavanones/pharmacology , Oxidative Stress/drug effects , Animals , Apoptosis , Caspase 12/metabolism , Diabetes Mellitus, Experimental , Heat-Shock Proteins/metabolism , Male , Malondialdehyde/metabolism , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Transcription Factor CHOP/metabolism
17.
Microb Pathog ; 110: 240-244, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28687324

ABSTRACT

Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 µg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection.


Subject(s)
Antiviral Agents/pharmacology , Caffeic Acids/pharmacology , Distemper Virus, Canine/drug effects , Distemper/drug therapy , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Caffeic Acids/administration & dosage , Caffeic Acids/chemistry , Caffeic Acids/therapeutic use , Chlorocebus aethiops , Distemper/virology , Dose-Response Relationship, Drug , Drug Combinations , Inhibitory Concentration 50 , RNA, Viral/metabolism , Ribavirin/pharmacology , Ribavirin/therapeutic use , Time Factors , Vero Cells/drug effects , Virus Replication/drug effects
18.
Mutagenesis ; 32(6): 599-606, 2017 12 31.
Article in English | MEDLINE | ID: mdl-29346610

ABSTRACT

Autosomal recessive woolly hair/hypotrichosis (ARWH/HT: OMIM #278150/604379) is a rare hereditary hair disease characterized by tightly curled hair at birth which can lead to sparse hair later in life. The mutations in both LIPH and LPAR6/P2RY5 are responsible for autosomal recessive woolly hair with or without hypotrichosis (ARWH/HT). To conduct clinical and genetic investigations in four patients from three unrelated Chinese Han families with ARWH/HT, we performed mutation screening of LIPH and LPAR6/P2RY5 gene and identified four mutations in LIPH: c.454G>A, c.614A>G, c.736T>A, c.742C>A. c.736T>A and c.742C>A mutations were reported in previous studies, and c.454G>A, c.614A>G were identified for the first time. We carried out functional studies of the two mutants with c.454G>A (p.Gly152Arg, G152R) or c.614A>G (p.His205Arg, H205R). Interestingly, both of them lead to secretion defects of LIPH, which are involved in the pathogenesis of ARWH/HT.


Subject(s)
Asian People/genetics , Genes, Recessive , Genetic Predisposition to Disease , Hair Diseases/genetics , Hair/abnormalities , Hypotrichosis/genetics , Lipase/genetics , Mutation/genetics , Amino Acid Sequence , Autoantigens/genetics , Base Sequence , Child , Child, Preschool , Female , HEK293 Cells , Humans , Lipase/chemistry , Male , Pedigree , Ribonucleoproteins/genetics , SS-B Antigen
19.
PLoS Biol ; 12(3): e1001820, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24667537

ABSTRACT

Cognitive and behavioral disorders are thought to be a result of neuronal dysfunction, but the underlying molecular defects remain largely unknown. An important signaling pathway involved in the regulation of neuronal function is the cyclic AMP/Protein kinase A pathway. We here show an essential role for coronin 1, which is encoded in a genomic region associated with neurobehavioral dysfunction, in the modulation of cyclic AMP/PKA signaling. We found that coronin 1 is specifically expressed in excitatory but not inhibitory neurons and that coronin 1 deficiency results in loss of excitatory synapses and severe neurobehavioral disabilities, including reduced anxiety, social deficits, increased aggression, and learning defects. Electrophysiological analysis of excitatory synaptic transmission in amygdala revealed that coronin 1 was essential for cyclic-AMP-protein kinase A-dependent presynaptic plasticity. We further show that upon cell surface stimulation, coronin 1 interacted with the G protein subtype Gαs to stimulate the cAMP/PKA pathway. The absence of coronin 1 or expression of coronin 1 mutants unable to interact with Gαs resulted in a marked reduction in cAMP signaling. Strikingly, synaptic plasticity and behavioral defects of coronin 1-deficient mice were restored by in vivo infusion of a membrane-permeable cAMP analogue. Together these results identify coronin 1 as being important for cognition and behavior through its activity in promoting cAMP/PKA-dependent synaptic plasticity and may open novel avenues for the dissection of signal transduction pathways involved in neurobehavioral processes.


Subject(s)
Behavior, Animal , Cognition/physiology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Microfilament Proteins/physiology , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/genetics , Animals , Brain/metabolism , Brain/pathology , Humans , Memory , Mice , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Signal Transduction , Social Behavior
20.
J Nat Prod ; 80(1): 156-161, 2017 01 27.
Article in English | MEDLINE | ID: mdl-28032759

ABSTRACT

Six new iridal-type triterpenoids containing an unprecedented cyclopentane ring, polycycloiridals E-J (1-6), were isolated from a large-scale re-extraction of Iris tectorum. A possible biosynthesis pathway is postulated. The known spirioiridotectal D (7) was also obtained in the current investigation, and its structure was unequivocally defined using X-ray diffraction data. Compound 7 suppressed LPS-activated NO production in the BV2 cell line with an IC50 value of 0.54 µM.


Subject(s)
Cyclopentanes/isolation & purification , Iris Plant/chemistry , Rhizome/chemistry , Triterpenes/isolation & purification , Cyclopentanes/chemistry , Cyclopentanes/pharmacology , Molecular Structure , Plant Extracts/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , X-Ray Diffraction
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