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1.
Int J Biol Macromol ; 277(Pt 4): 134501, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111483

ABSTRACT

This study employs an optimized and environmentally friendly method to extract and purify chondroitin sulfate (CS) from bovine nasal cartilage using enzymatic hydrolysis, ethanol precipitation, and DEAE Sepharose Fast Flow column chromatography. The extracted CS, representing 44.67 % ± 0.0016 of the cartilage, has a molecular weight of 7.62 kDa. Characterization through UV, FT-IR, NMR spectroscopy, and 2-aminoacridone derivatization HPLC revealed a high content of sulfated disaccharides, particularly ΔDi4S (73.59 %) and ΔDi6S (20.61 %). Interaction studies with bovine serum albumin (BSA) using fluorescence spectroscopy and molecular docking confirmed a high-affinity, static quenching interaction with a single binding site, primarily mediated by van der Waals forces and hydrogen bonding. The interaction did not significantly alter the polarity or hydrophobicity of BSA aromatic amino acids. These findings provide a strong foundation for exploring the application of CS in tissue engineering and drug delivery systems, leveraging its unique interaction with BSA for targeted delivery and enhanced efficacy.


Subject(s)
Chondroitin Sulfates , Nasal Cartilages , Serum Albumin, Bovine , Animals , Cattle , Chondroitin Sulfates/chemistry , Molecular Docking Simulation , Molecular Weight , Nasal Cartilages/chemistry , Nasal Cartilages/metabolism , Protein Binding , Serum Albumin, Bovine/chemistry
2.
BioDrugs ; 38(5): 681-689, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39080181

ABSTRACT

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).


Subject(s)
Antibodies, Monoclonal, Humanized , Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Adult , Male , Female , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Middle Aged , Treatment Outcome , Severity of Illness Index , Young Adult , Interleukin-4 Receptor alpha Subunit/antagonists & inhibitors
3.
Int J Biol Macromol ; 260(Pt 1): 129499, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38262829

ABSTRACT

Chondroitin sulfate (CS) was extracted and purified from shark cartilage, and its interaction with bovine serum albumin (BSA) were studied. The content of chondroitin sulfate in shark cartilage was 29.97 % using the 1,9-dimethyl-methylene blue method. The molecular weight of CS was determined to be 62.464 kDa by high-performance gel permeation chromatography. UV and FT-IR spectroscopy identified the characteristics of CS and its functional group information. NMR spectroscopy and disaccharide derivatization revealed that CS was predominantly composed of disulfated disaccharides, specifically ΔDi4,6S. Fluorescence quenching experiments indicated that the interaction between CS and BSA exhibited static quenching, with a binding site number of 1. The binding process was primarily mediated by van der Waals forces and hydrogen bonds. Furthermore, synchronous and 3D fluorescence spectroscopy demonstrated that CS had minimal impact on the polarity and hydrophobicity of the microenvironment surrounding Tyr and Trp residues. UV-vis absorption and circular dichroism (CD) spectroscopy demonstrated the altered structure of BSA. The molecular docking analysis revealed that CS formed hydrogen bonds and salt bridges with BSA, predominantly binding to the IIA substructure domain of BSA. Investigating the interaction between CS and BSA holds the potential for enhancing its applications in drug delivery and tissue engineering endeavors.


Subject(s)
Serum Albumin, Bovine , Sharks , Animals , Molecular Docking Simulation , Serum Albumin, Bovine/chemistry , Chondroitin Sulfates/metabolism , Spectroscopy, Fourier Transform Infrared , Thermodynamics , Spectrometry, Fluorescence/methods , Binding Sites , Cartilage/metabolism , Protein Binding , Circular Dichroism
4.
Medicine (Baltimore) ; 101(40): e30941, 2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36221401

ABSTRACT

To investigate the predictive value of neuron-specific enolase (NSE) on intensive care unit (ICU) mortality in patients with septic shock. Seventy-five patients with septic shock hospitalized in the emergency intensive care unit (EICU) of Hebei General Hospital from March 2020 to September 2021 were included, and the patients' baseline characteristics and laboratory findings were collected. NSE levels on the first and fourth days after admission were retrieved. NSE% [(NSEday1 - NSEday4)/NSEday1 × 100%] and δNSE (NSEday1 - NSEday4) were calculated. The outcome indicator was ICU mortality. The patients were divided into the survivors group (n = 57) and the nonsurvivors group (n = 18). Multivariate analysis was performed to assess the relationship between NSE and ICU mortality. The predictive value of NSE was evaluated using receiver operating characteristic (ROC) curve. There were no significant differences in age, gender, systolic blood pressure (SBP), heart rate (HR), acute physiology and chronic health evaluation II score (APACHE II score), source of infection, and comorbidities between the 2 groups (all P > .05). Interleukin-6 (IL-6), NSE (day1), and NSE (day4) were significantly higher in patients in the nonsurvivors group (all P < .05), and there were no statistical differences in other laboratory tests between the 2 groups (all P > .05). APACHE II score, IL-6, lactate (Lac), total bilirubin (TBil), NSE (day1), and NSE (day4) showed a weak positive correlation with ICU mortality in patients with septic shock (all P < .05). Multivariate logistic regression analysis demonstrated that APACHE II score (odds ratio [OR] = 1.166, 95% confidence interval [95% confidence interval [CI]] 1.005-1.352, P = .042), IL-6 (OR = 1.001, 95% CI 1.000-1.001, P = .003) and NSE (day4) (OR = 1.099, 95% CI 1.027-1.176, P = .006) were independently associated with the ICU mortality of sepsis shock patients. The area under the curve (AUCs) of APACHE II score, IL-6, NSE (day1), and NSE (day4) for predicting prognosis were 0.650, 0.694, 0.758 and 0.770, respectively (all P < .05). NSE(day4) displayed good sensitivity and specificity (Sn = 61.11%, Sp = 91.23%) for predicting ICU mortality with a cutoff value of 25.94 ug/L. High-level NSE (day4) is an independent predictor of ICU mortality in sepsis shock patients, which may become a good alternate option for evaluating sepsis severity. More extensive studies are needed in the future to demonstrate the prognosis value of NSE.


Subject(s)
Sepsis , Shock, Septic , Bilirubin , Humans , Intensive Care Units , Interleukin-6 , Lactic Acid , Phosphopyruvate Hydratase , Prognosis , ROC Curve , Retrospective Studies
6.
J Pharm Biomed Anal ; 205: 114339, 2021 Oct 25.
Article in English | MEDLINE | ID: mdl-34464868

ABSTRACT

This study was designed to explore the sulfation patterns of chondroitin sulfate (CS)/dermatan sulfate (DS), and keratan sulfate (KS) and the expression of carbohydrate sulfotransferases (CHSTs) in 26 pancreatic tumor and normal tissues. CS/DS and KS profiles were simultaneously determined. Pancreatic tumor tissues exhibited increased ΔDi-0S, ΔDi-4S, and ΔDi-6S levels, with absolute ΔDi-4S content being highest, followed by ΔDi-6S. However, as for the contents of KS-6S and KS-6S,6'S, there were no significant regular change. The expression levels of CHST1 and CHST4 were 37 and 15 times higher than those in normal tissues. PCA and OPLS-DA revealed that ΔDi-4S and ΔDi-6S levels could be reliably used to differentiate between healthy and cancerous tissues. The up-regulation of CHST3, CHST12, CHST13, and CHST15 was directly correlated with C-4 and C-6 sulfation. These data provide a foundation for future studies of the role of ΔDi-4S and ΔDi-6S in the progression of pancreatic cancer.


Subject(s)
Keratan Sulfate , Pancreatic Neoplasms , Chondroitin Sulfates , Dermatan Sulfate , Humans , Membrane Glycoproteins , Sulfates , Sulfotransferases/genetics
8.
Rapid Commun Mass Spectrom ; 35(1): e8959, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33001505

ABSTRACT

RATIONALE: Iris tectorum Maxim. is a traditional medicinal herb that is commonly used to treat inflammatory conditions. The present study investigated the fragmentation patterns of isoflavone glycosides and their qualitative analysis. In addition, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used to evaluate the anti-inflammatory properties of I. tectorum Maxim. samples collected at different time points during the year. METHODS: High-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (HPLC/QTOF-MS/MS) and HPLC with diode-array detection were employed for qualitative and quantitative analysis. The fragmentation patterns of the isoflavones were observed in negative electrospray ionization mode with collision-induced dissociation (CID). Their anti-inflammatory activity was assessed via nitric oxide (NO) production in LPS-treated RAW264.7 macrophages. RESULTS: A total of 15 chemical components were observed and tentatively identified using HPLC/QTOF-MS/MS. At low collision energy, the relative abundances of the aglycone radical anions Y0 - , [Y0 - H]-• , [Y0 - CH3 ]-• and [Y0 - H- CH2 ]-• were used for the structural characterization of tectoridin and tectorigenin-4'-O-ß-D-glucoside. The radical ions [Y0 - CH3 ]-• and [Y0 - H - 2CH3 ]-• were also employed to differentiate between iristectorin A and iristectorin B based upon their high-energy CID spectra. Levels of 9.02 mg/g of tectoridin and 1.04 mg/g of tectorigenin were found in samples collected in June, which exhibited 69.7% NO inhibitory activity. CONCLUSIONS: The characteristic fragmentation patterns enabled us to reliably identify isoflavone glycosides. The results of the quantitative determination and NO inhibitory activity offer insight into the optimal I. tectorum Maxim. harvesting time.


Subject(s)
Glycosides/analysis , Iris Plant/chemistry , Isoflavones/analysis , Nitric Oxide/metabolism , Plants, Medicinal/chemistry , Animals , Anti-Inflammatory Agents/analysis , Chromatography, High Pressure Liquid/methods , Mice , Nitric Oxide/analysis , Plant Extracts/chemistry , RAW 264.7 Cells , Tandem Mass Spectrometry/methods
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 546-550, 2019 Jul.
Article in Chinese | MEDLINE | ID: mdl-31642233

ABSTRACT

OBJECTIVE: To investigate the expression of stearoyl-CoA desaturase-1 (SCD1) in breast cancer cell lines. To analyze the effect of inhibiting SCD1 activity on the proliferation and cell cycle of MCF-7 breast cancer cell and its mechanism. METHODS: The expression of SCD1 protein were detected by Western blot techniques in breast cancer cell lines and humanskin fibroblasts.Cell viability of MCF-7 cells treated with MF-438 was measured using MTS assay and IC50 value was calculated.The distribution of cell cycle was determined by PI staining using flow cytometry.The expression of Cyclin D1 was detected by Western blot. The expression of Akt, pAkt, pAMPK and pACC were also detected by Western blot. RESULTS: The expression level of SCD1 in MCF-7 and MDA-MB-231 cells was significantly higher than that in HSF cells (P < 0.05).MF-438 showed a significant dose-dependent proliferation inhibition effect on MCF-7 cells cultured in low serum at a concentration ranging from 100 nmol/L to 100 µmol/L with an IC50 value of (3.9±0.45) µmol/L. After intervention of 5 µmol/L MF-438 in MCF-7 cells, the proportion of cells in S phase and G2/M phase was significantly decreased (P < 0.01), the proportion of cells in G0/G1 phase increased (P < 0.01), and the expression of Cyclin D1 was significantly decreased (P < 0.05); Meanwhile, the expression of pAkt and pAkt/Akt value were significantly decreased (P < 0.05) and the expression of pAMPK and pACC levels were significantly increased (P < 0.05). CONCLUSIONS: SCD1 plays an important role in the occurrence and development of breast cancer. Inhibition of SCD1 activity can inhibit cell cycle progression and impair cell proliferation by down-regulating the Akt pathway and activating the AMPK pathway. Further research on SCD1 is expected to provide a new target for molecular targeted therapy of breast cancer.


Subject(s)
Breast Neoplasms/pathology , Cell Cycle , Cell Proliferation , Stearoyl-CoA Desaturase/genetics , AMP-Activated Protein Kinase Kinases , Cell Division , Cyclin D1/metabolism , Humans , MCF-7 Cells , Protein Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stearoyl-CoA Desaturase/antagonists & inhibitors
10.
Skin Res Technol ; 25(6): 835-838, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31215072

ABSTRACT

BACKGROUND: Clinically, depigmentation after local corticosteroid injection is not rare. But there are less articles about its reflectance confocal microscopy (RCM) and histological features. This study aimed to define the RCM features and histopathologic findings of hypopigmentation after local corticosteroid injection and to analyze the correlations between the above two methods. METHODS: Forty cases with hypopigmentation after local corticosteroid injection were used to analyze the clinical and RCM features. Subsequently, for 20 of 40, an excision biopsy of the same imaged areas for histopathologic examination was executed. RESULTS: Our results showed that all 40 cases had round or ellipse hypopigmented macules with obscure boundary and 26 of 40 lesions' long diameter went along limbs. The RCM features and the histological findings revealed all patients had variable degrees of epidermal thinning, flattening rete ridges, reduced melanin, and no inflammatory cell infiltration. MART-1 analysis revealed the number of melanocytes was normal but with no or less melanin by Fontana-Masson staining. CONCLUSIONS: Depigmentation after local corticosteroid injection was a kind of disease with intact melanocytes, whose function was impaired. RCM features offer a high consistency with histopathologic findings. It thus constitutes a promising adjuvant tool for its diagnosis and for therapeutic follow-up.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Hypopigmentation , Microscopy, Confocal/methods , Skin , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Female , Histocytochemistry , Humans , Hypopigmentation/chemically induced , Hypopigmentation/diagnostic imaging , Hypopigmentation/pathology , Injections, Intradermal/adverse effects , Male , Middle Aged , Skin/chemistry , Skin/diagnostic imaging , Skin/pathology
11.
Math Biosci Eng ; 16(2): 1021-1033, 2019 01 30.
Article in English | MEDLINE | ID: mdl-30861677

ABSTRACT

Recently, Chen and Ma [A generalized shift-splitting preconditioner for saddle point problems, Applied Mathematics Letters, 43 (2015) 49-55] introduced a generalized shift-splitting preconditioner for saddle point problems with symmetric positive definite (1,1)-block. In this paper, I establish a parameterized shift-splitting preconditioner for solving the large sparse augmented systems of linear equations. Furthermore, the preconditioner is based on the parameterized shift-splitting of the saddle point matrix, resulting in an unconditional convergent fixed-point iteration, which has the intersection with the generalized shift-splitting preconditioner. In final, one example is provided to confirm the effectiveness.


Subject(s)
Computational Biology/methods , Computer Simulation , Algorithms , Finite Element Analysis , Least-Squares Analysis , Linear Models , Models, Cardiovascular
12.
Physiol Genomics ; 51(5): 159-168, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30925122

ABSTRACT

Fish sex-determining mechanisms can be classified as genotypic (GSD), temperature (TSD), or genotypic plus temperature effects (GSD+TE). Previous studies have shown that culturing water temperature during thermosensitive periods (TSP) could affect the expression of many genes in the gonad in some fish. However, few studies have focused on gene expression changes in the brain after temperature treatment during TSP in fish species. In this study, three families were developed by crossing XX neomales with XX females and one of them was used for transcriptome analysis. The results showed that a total of 105, 3164 and 4666 DEGs were respectively obtained in FC (female control) vs. FT (high temperature-treated females at TSP), FC vs. MC (male control), and MC vs. FT comparison groups. By profiling analysis, we show that the mRNA expression levels of 16 differentially expressed genes (DEGs) exhibited significant downregulation or upregulation after high temperature treatment and reached a similar level as that in MC. Among the 16 DEGs, LOC100699848 (lysine specific demethylase 6A) and Jarid2 contained JmjC domain, showing the possible important role of JmjC domain in response to temperature treatment in Nile tilapia. Kdm6b (lysine demethylase 6B) and Jarid2 have been shown to play important roles in reptile TSD, showing the relative conservation of underlying regulation mechanisms between TSD in reptile and TSD or GSD+TE in fish species. Finally, the transcriptome profiling was validated by quantitative real-time PCR in nine selected genes. These results provide a direction for investigating the GSD+TE molecular mechanism in fish species.


Subject(s)
Gene Expression Profiling/methods , Animals , Cichlids/genetics , Cichlids/metabolism , Female , Genotype , Gonads/cytology , Gonads/metabolism , Male , Polymerase Chain Reaction , Sex Determination Processes/genetics , Sex Determination Processes/physiology , Temperature
14.
Pharm Biol ; 56(1): 94-103, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29316840

ABSTRACT

CONTEXT: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)]. OBJECTIVE: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model. MATERIALS AND METHODS: Sixty male rats were divided into five experimental groups: a normal control group (CTR + vehicle), a control group administered MOTILIPERM 200 mg/kg (CTR + M 200), a varicocele-induced control group (VC + vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC + M 100) or 200 (VC + M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG). RESULTS: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC + M 200 group compared with VC + vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio. DISCUSSION AND CONCLUSIONS: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.


Subject(s)
Antioxidants/therapeutic use , Endoribonucleases/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Multienzyme Complexes/metabolism , Plant Extracts/therapeutic use , Protein Serine-Threonine Kinases/metabolism , Varicocele/metabolism , Varicocele/prevention & control , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Male , Phosphorylation/drug effects , Phosphorylation/physiology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , Testis/drug effects , Testis/metabolism
16.
Oncol Rep ; 38(2): 1005-1012, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28656258

ABSTRACT

Laryngeal carcinoma is one of the most common malignant tumors in otorhinolaryngology. Moreover, experimental investigation showed that cancerous inhibitor of protein phosphatase 2A (CIP2A) expressed highly in various cancers. Therefore, we investigated whether CIP2A can regulate the proliferation, invasion and migration by RNA interference in Hep-2 cells and AMC-NH-8 cells and further affect the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Overexpression of CIP2A was evaluated in tumor tissue and laryngeal cancer cell lines (Hep-2 and AMC-NH-8 cells) by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. In a follow-up experiment, we confirmed that CIP2A siRNA effectively suppressed the cell proliferation at 48 and 72 h, and arrested cell cycle at G0/G1 in Hep-2 cells and AMC-NH-8 cells. The invasion and migration of cell in siRNA CIP2A group were markedly inhibited. Moreover, the experimental results showed that the expression levels of invasion- and migration-related genes, including E-cadherin, metastasis-associated gene 1 (MTA1) and matrix metalloproteinases-2/9 (MMP-2/9), were regulated by CIP2A siRNA. Phosphorylation levels of PI3K and AKT proteins were reduced by CIP2A siRNA. Importantly, it suggested signaling through PI3K/Akt as a critical mechanism by which CIP2A siRNA may suppress cell proliferation, invasion and migration in laryngeal carcinoma cells.


Subject(s)
Autoantigens/metabolism , Biomarkers, Tumor/metabolism , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/pathology , Membrane Proteins/metabolism , Apoptosis , Autoantigens/genetics , Biomarkers, Tumor/genetics , Female , Follow-Up Studies , Humans , Intracellular Signaling Peptides and Proteins , Laryngeal Neoplasms/metabolism , Male , Membrane Proteins/genetics , Middle Aged , Neoplasm Invasiveness , Phosphorylation , Prognosis , Survival Rate , Tumor Cells, Cultured
17.
Mol Plant ; 10(1): 131-142, 2017 01 09.
Article in English | MEDLINE | ID: mdl-27746301

ABSTRACT

The mechanism by which the mitochondrial alternative oxidase (AOX) pathway contributes to photosystem II (PSII) photoprotection is in dispute. It was generally thought that the AOX pathway protects photosystems by dissipating excess reducing equivalents exported from chloroplasts through the malate/oxaloacetate (Mal/OAA) shuttle and thus preventing the over-reduction of chloroplasts. In this study, using the aox1a Arabidopsis mutant and nine other C3 and C4 plant species, we revealed an additional action model of the AOX pathway in PSII photoprotection. Although the AOX pathway contributes to PSII photoprotection in C3 leaves treated with high light, this contribution was observed to disappear when photorespiration was suppressed. Disruption or inhibition of the AOX pathway significantly decreased the photorespiration in C3 leaves. Moreover, the AOX pathway did not respond to high light and contributed little to PSII photoprotection in C4 leaves possessing a highly active Mal/OAA shuttle but with little photorespiration. These results demonstrate that the AOX pathway contributes to PSII photoprotection in C3 plants by maintaining photorespiration to detoxify glycolate and via the indirect export of excess reducing equivalents from chloroplasts by the Mal/OAA shuttle. This new action model explains why the AOX pathway does not contribute to PSII photoprotection in C4 plants.


Subject(s)
Arabidopsis/metabolism , Mitochondrial Proteins/metabolism , Oxidoreductases/metabolism , Photosystem II Protein Complex/metabolism , Plant Proteins/metabolism , Arabidopsis/genetics , Arabidopsis/radiation effects , Electron Transport , Light , Metabolic Networks and Pathways , Mitochondrial Proteins/genetics , Models, Biological , Mutation , Oxidoreductases/genetics , Photosystem II Protein Complex/genetics , Plant Leaves/metabolism , Plant Leaves/radiation effects , Plant Proteins/genetics
18.
Clin Interv Aging ; 11: 1301-1307, 2016.
Article in English | MEDLINE | ID: mdl-27698559

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of tamsulosin hydrochloride 0.2 mg (TAM) and its combination with solifenacin succinate 5 mg (SOL) after transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The patients were randomized into three groups: TURP (group 1), TURP plus TAM (group 2), and TURP plus TAM + SOL (group 3). Patients in group 2 and group 3 received medication for 4 weeks. The primary efficacy end points were the mean change in total International Prostate Symptom Score (IPSS) and IPSS subscores. The secondary end points included quality-of-life score, Overactive Bladder Symptom Score, and short-form voiding and storage score of International Continence Society. RESULTS: In total, 37 men (31.8%) in group 1, 37 men (31.8%) in group 2, and 42 men (36.2%) in group 3 completed the study. In total IPSS, no significant improvement was seen from baseline to the end of treatment in groups 2 and 3 compared with group 1. However, in group 2, the decrement in the IPSS storage score was smaller than group 1 (P=0.02), and in group 3, the decrement in the IPSS voiding score was smaller than group 1 (P=0.05). In groups 2 and 3 compared with group 1, improvements in the quality of life score, total score of Overactive Bladder Symptom Score, and short-form voiding score and storage score of International Continence Society were not statistically significant. CONCLUSION: Treatment with TAM and combination of TAM and SOL did not have significant additional benefits for lower urinary tract symptoms during the early recovery period after TURP.


Subject(s)
Lower Urinary Tract Symptoms/drug therapy , Lower Urinary Tract Symptoms/etiology , Solifenacin Succinate/therapeutic use , Sulfonamides/therapeutic use , Transurethral Resection of Prostate/adverse effects , Urological Agents/therapeutic use , Aged , Aged, 80 and over , Drug Therapy, Combination , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Solifenacin Succinate/administration & dosage , Solifenacin Succinate/adverse effects , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Tamsulosin , Treatment Outcome , Urinary Bladder, Overactive/drug therapy , Urological Agents/administration & dosage , Urological Agents/adverse effects
19.
Int J Urol ; 23(3): 259-65, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26646436

ABSTRACT

OBJECTIVES: To investigate the effect of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid, a new benzofuroindole derivative, on the intraurethral pressure in a rat model of benign prostatic hyperplasia. METHODS: Benign prostatic hyperplasia was induced by testosterone and 17ß-estradiol, which were administered intramuscularly once a day for 12 weeks. The effects of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid and tamsulosin on the intraurethral pressure induced by the electrostimulation of hypogastric nerves after a single intravenous injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (10 mg/kg) or tamsulosin (10 µg/kg) were evaluated in a benign prostatic hyperplasia model. The electrostimulation-induced intraurethral pressure was measured just before and after the injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid. Bodyweight and genitourinary organ weights were recorded, and serums and tissues were subjected to hormone assays and histopathology. In addition, the expression of α1-adrenoceptors in the prostate was measured by western blotting. RESULTS: The benign prostatic hyperplasia groups showed increased prostatic index, increased concentrations of testosterone, free testosterone and estradiol in serum, and increased epithelial thickness of the prostate. An injection of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin significantly inhibited the elevation of electrostimulation-induced intraurethral pressure. In addition, 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid did not cause a significant change in the blood pressure compared with tamsulosin. While the benign prostatic hyperplasia group showed increased the expression of α1-adrenoceptors, the 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid or tamsulosin injection into a rat model of benign prostatic hyperplasia decreased the expression of α1-adrenoceptors. CONCLUSIONS: These findings show that 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid might be beneficial for lowering the intraurethral pressure associated with benign prostatic hyperplasia, and it could represent a therapeutic option for benign prostatic hyperplasia patients.


Subject(s)
Benzofurans/pharmacology , Indoles/pharmacology , Prostatic Hyperplasia/drug therapy , Sulfonamides/pharmacology , Urethra/drug effects , Animals , Benzofurans/administration & dosage , Disease Models, Animal , Electric Stimulation , Estradiol/blood , Estradiol/pharmacology , Humans , Indoles/administration & dosage , Male , Pressure , Prostatic Hyperplasia/physiopathology , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha-1/metabolism , Sulfonamides/administration & dosage , Tamsulosin
20.
J Urol ; 195(4 Pt 1): 1057-64, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26519655

ABSTRACT

PURPOSE: In this study we investigated if testosterone undecanoate attenuates anemia and the risk of cardiovascular disease in patients with hypogonadism. MATERIALS AND METHODS: A registry study consisted of 58 participants with a subnormal total testosterone level (less than 2.35 ng/ml) and at least mild symptoms of testosterone deficiency. All patients received an injection of 1,000 mg testosterone undecanoate at the initial visit, followed by injection at 6, 18, 30, 42 and 54 weeks. Serum hormones, hemoglobin, hematocrit, anemia risk factors, lipid profiles, whole blood viscosity and anthropometry were measured. RESULTS: Total testosterone (from mean ± SD 1.87 ± 1.09 to 5.52 ± 1.92 ng/ml, p <0.001) and free testosterone (from 3.04 ± 2.03 to 7.23 ± 2.90 pg/ml, p <0.001) were restored by testosterone undecanoate therapy. Hemoglobin and hematocrit significantly increased after testosterone undecanoate therapy by an average of 2.46 gm/dl (p <0.001) and 3.03% (p <0.001), respectively. The prevalence of anemia (from 29.6% to 10.0%) significantly decreased (p <0.001) and patients with anemia showed a significant increase in erythropoietin after testosterone undecanoate therapy (p = 0.047). A reduction in total cholesterol (from 165.89 ± 39.16 to 153.80 ± 154.27 mg/dl, p = 0.002), increased whole blood viscosity and increased hematocrit were observed until 54 weeks compared with baseline. However, whole blood viscosity and hematocrit stabilized after 18 weeks. CONCLUSIONS: After 54 weeks testosterone undecanoate decreased the prevalence of anemia and components of the metabolic syndrome. A longer duration of testosterone undecanoate therapy of more than 18 weeks may be effective and safe in reducing blood viscosity and improving anemia.


Subject(s)
Androgens/therapeutic use , Anemia/drug therapy , Hormone Replacement Therapy , Hypogonadism/etiology , Testosterone/analogs & derivatives , Adolescent , Adult , Aged , Aged, 80 and over , Anemia/etiology , Cardiovascular Diseases/epidemiology , Humans , Hypogonadism/complications , Male , Middle Aged , Registries , Risk Factors , Testosterone/therapeutic use , Time Factors , Young Adult
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