Cooperative Cu/azodiformate system-catalyzed allylic C-H amination of unactivated internal alkenes directed by aminoquinoline.

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

Bronchial oncocytic carcinoma in an adult: a case report and literature review.

BACKGROUND: Lung salivary-type tumors originating from bronchial submucosal glands are rare, only four types of salivary gland-type tumors are listed in 2015 WHO classification of lung tumors. Here, we report a rare case of oncocytic carcinoma (OC) in the right main bronchus. CASE PRESENTATION: A 34-year-old man presented to our hospital with a two-month history of recurrent hemoptysis and with one month of inspiratory dyspnea. Pulmonary function tests showed mild restrictive ventilatory dysfunction and severe diffusion dysfunction. Furthermore, the flow volume loop showed a variable extra-thoracic obstruction. Computed tomography (CT) of the chest revealed that a polypiform nodule of 13 mm in diameter was at the proximal right main bronchus. Testing for purified protein derivative was positive (category 2). The nodule was resected under bronchoscopy. The bronchial aspirate was negative for mycobacterium tuberculosis and tumor cells. The biopsy sample showed a solid and acinar predominant pattern with abundant eosinophilic cytoplasm. The bronchial mucosa was destroyed and replaced by tumor cells. The loose edematous stromal reaction could be seen in a local area. Immunohistochemically, tumor cells were positive for CK, EMA, Vimentin, CD117, CK7, S100, Mammaglobin and SOX10. Only scattered tumor cells were stained by basal cell markers, including CK5/6, P40 and P63. Electron microscopy revealed numerous swelling mitochondria with lacking mitochondrial cristae in tumor cells. Fluorescence in situ hybridization (FISH) testing for MAML2 and ETV6 rearrangement were negative. Next-generation sequencing analysis of 520 genes in the tissue biopsy specimen showed no somatic mutation. The diagnosis of OC was made. Subsequently, the patient underwent a right upper lobectomy with sleeve resection of the main bronchus and lymph dissection. No recurrent evidence was seen during two years of chest CT follow-up. CONCLUSIONS: To our knowledge, this is the first case of primary OC in the bronchus. This patient has no recurrence during two years of follow-up, indicating that primary OC in the bronchus has the same favorable prognosis as in salivary glands. Moreover, complete excision and thorough sampling to know the invasive growth pattern is important to reach the correct diagnosis.

Efficacy of cecal retroflexion observed on adenoma missing of ascending colon during colonoscopy: A prospective, randomized, pilot trial.

BACKGROUND: Although colonoscopic retroflexion has been proved effective in reducing missed adenomas, there is still a lack of comprehensive and in-depth research focused on the ascending colon. We aimed to conduct a randomized controlled trial and tandem colonoscopy to investigate whether cecal retroflexion observed during colonoscopy can reduce missed adenomas in the ascending colon. METHODS: Men and women required to be between 45 and 80 years of age were screened for enrollment in the trial. Patients were randomly assigned according to a 1:1 ratio to either the trial group or control group. Patients in the trial group underwent 2 forward examination and a cecal retroflexion observed in the ascending colon, while patients in the control group underwent only 2 forward examinations in the ascending colon. The primary outcome was adenoma miss rate. The secondary outcomes contained adenoma detection rate, polyp miss rate, polyp detection rate, insertion time and withdrawal time. Differences between groups in the primary outcome and in the other categorical indicators were tested using chi-squared test and Fisher exact test. For the comparison of continuous outcomes, the Student t test was applied. RESULTS: A total of 60 subjects were eligible for the study between April to June 2020, of which 55 were randomized and eligible for analysis (26 to the control group and 29 to the trial group). The characteristics of patients were no significant differences statistically between the trial group and the control group. Similarly, the characteristics of the colonoscopy procedures included cecal insertion distance, the length of cecum and ascending colon, insertion time, withdrawal time, quality of bowel preparation, numerical rating scale for pain, polyps detected, and adenomas detected, and there were no significant differences statistically between the 2 groups (P = .864, P = .754, P = .700, P = .974, P = .585, P = .835, P = .373, P = .489). The characteristics of the polyps were also no significant differences statistically between the 2 groups. CONCLUSION: This pilot trial failed to show benefit of cecal retroflexion observed on adenoma missing of ascending colon during colonoscopy; however, further conclusions require a prospective study with a higher level of evidence. (NCT03355443).

Comparison and fusion prediction model for lung adenocarcinoma with micropapillary and solid pattern using clinicoradiographic, radiomics and deep learning features.

To investigate whether the combination scheme of deep learning score (DL-score) and radiomics can improve preoperative diagnosis in the presence of micropapillary/solid (MPP/SOL) patterns in lung adenocarcinoma (ADC). A retrospective cohort of 514 confirmed pathologically lung ADC in 512 patients after surgery was enrolled. The clinicoradiographic model (model 1) and radiomics model (model 2) were developed with logistic regression. The deep learning model (model 3) was constructed based on the deep learning score (DL-score). The combine model (model 4) was based on DL-score and R-score and clinicoradiographic variables. The performance of these models was evaluated with area under the receiver operating characteristic curve (AUC) and compared using DeLong's test internally and externally. The prediction nomogram was plotted, and clinical utility depicted with decision curve. The performance of model 1, model 2, model 3 and model 4 was supported by AUCs of 0.848, 0.896, 0.906, 0.921 in the Internal validation set, that of 0.700, 0.801, 0.730, 0.827 in external validation set, respectively. These models existed statistical significance in internal validation (model 4 vs model 3, P = 0.016; model 4 vs model 1, P = 0.009, respectively) and external validation (model 4 vs model 2, P = 0.036; model 4 vs model 3, P = 0.047; model 4 vs model 1, P = 0.016, respectively). The decision curve analysis (DCA) demonstrated that model 4 predicting the lung ADC with MPP/SOL structure would be more beneficial than the model 1and model 3 but comparable with the model 2. The combined model can improve preoperative diagnosis in the presence of MPP/SOL pattern in lung ADC in clinical practice.

ZY-444 inhibits the growth and metastasis of prostate cancer by targeting TNFAIP3 through TNF signaling pathway.

Prostate cancer is one of the most lethal malignancies, and androgen deprivation therapy remains the mainstay of treatment for prostate cancer patients. Although androgen deprivation can initially come to remission, the disease often develops into castration-resistant prostate cancer (CRPC), which is still dependent on androgen receptor (AR) signaling and is related to a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance uninterrupted emerges, and new therapies are urgently needed. In this study, we identified a potent small molecule compound, ZY-444, that suppressed PCa cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous. Transcriptome sequencing analysis showed that TNFAIP3 was significantly elevated in prostate cancer cells after ZY-444 treatment. Further studies through overexpression of TNFAIP3 confirmed that TNFAIP3, as a direct target gene of ZY-444, contributes to the functions of ZY-444. In addition, we demonstrated the effects of TNFAIP3 on prostate cancer cell apoptosis, migration and proliferation to elucidate the mechanism of ZY-444. We found that TNFAIP3 inhibited the TNF signaling pathway, which could inhibit cell migration and proliferation and contribute to apoptosis. Overall, these findings highlighted TNFAIP3 as a tumor suppressor gene in the regulation of the progression and metastatic potential of prostate cancer and that targeting TNFAIP3 by ZY-444 might be a promising strategy for prostate cancer treatment.

Effects of elevated atmospheric ammonia concentration on photosynthetic characteristics and grain yield in wheat under different nitrogen rates.

To evaluate the effects of nitrogen (N) application rates on the growth, photosynthetic traits and yield of winter wheat under elevated atmospheric ammonia (NH3) concentrations could provide guidance for N management under high NH3 environment. We conducted a split-plot experiment for two consecutive years (2020-2021 and 2021-2022) with top-open chambers. The treatments included two NH3 concentrations [elevated ambient NH3 concentration at 0.30-0.60 mg·m-3 (EAM) and air NH3 concentration at 0.01-0.03 mg·m-3 (AM)] and two N application rates [recommended N dose (+N) and no N application (-N)]. We analyzed the effects of aforementioned treatments on net photosynthetic rate (Pn), stomatal conductance (gs), chlorophyll content (SPAD value), plant height, and grain yield. The results showed that averaged across the two years, EAM significantly increased Pn, gs, and SPAD values at the jointing and booting stages at the -N level by 24.6%, 16.3%, 21.9% and 20.9%, 37.1%, 5.7%, respectively, compared with AM. However, EAM significantly decreased Pn, gs, and SPAD values at jointing and booting stages at +N level by 10.8%, 5.9%, 3.6% and 6.8%, 18.9%, 9.3%, respectively, over AM treatment. There was a significant effect of NH3 treatment, N application rates and their interaction on plant height and grain yield. Compared with AM, EAM increased the average plant height and grain yield by 4.5% and 32.1% at -N level and decreased by 1.1% and 8.5% at +N level, respectively. In a nutshell, the eleva-ted ambient NH3 concentration had positive effect on photosynthetic characteristics, plant height, and grain yield under ambient N condition, but a inhibitory effect under N application.

Modeling Syphilis and HIV Coinfection: A Case Study in the USA.

Syphilis and HIV infections form a dangerous combination. In this paper, we propose an epidemic model of HIV-syphilis coinfection. The model always has a unique disease-free equilibrium, which is stable when both reproduction numbers of syphilis and HIV are less than 1. If the reproduction number of syphilis (HIV) is greater than 1, there exists a unique boundary equilibrium of syphilis (HIV), which is locally stable if the invasion number of HIV (syphilis) is less than 1. Coexistence equilibrium exists and is stable when all reproduction numbers and invasion numbers are greater than 1. Using data of syphilis cases and HIV cases from the US, we estimated that both reproduction numbers for syphilis and HIV are slightly greater than 1, and the boundary equilibrium of syphilis is stable. In addition, we observed competition between the two diseases. Treatment for primary syphilis is more important in mitigating the transmission of syphilis. However, it might lead to increase of HIV cases. The results derived here could be adapted to other multi-disease scenarios in other regions.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Changes in patient peripheral blood cell microRNAs after total body irradiation during hematopoietic stem cell transplantation.

Background: Ionizing radiation exposure is a great threat to human health. MicroRNAs (miRNAs) have been shown to play an important role in radiation-induced biological effects. Here, we investigated plasma miRNA expression changes and differentially expressed miRNAs in radiotherapy patients exposed to cobalt-60 (60Co) gamma rays to provide an experimental basis for human plasma miRNAs as an estimation indicator for ionizing radiation injury. Methods: Six patients with acute lymphoblastic leukemia (ALL) received continuous 5 gray (Gy) total body irradiation (TBI) twice. At 12 hours after irradiation, miRNA microarray was applied to screen for differentially expressed miRNAs, with some miRNAs confirmed by real-time polymerase chain reaction (RT-PCR) assay. Bioinformatic analysis was carried out to identify the relevant target genes and biological function of the differentially expressed miRNAs. Results: After radiotherapy patients were exposed to 5 Gy gamma radiation, the expression of 9 plasma miRNAs was significantly upregulated, and the expression of 2 miRNAs was downregulated. After irradiation with 10 Gy gamma radiation, the blood plasma of radiotherapy patients contained 18 differentially expressed miRNAs, of which 17 were upregulated and 1 was downregulated (P<0.05). The expression of miR-4532, miR-4634, miR-4655-5p, miR-4763-3p, miR-4785, miR-6087, miR-6850-5p, and miR-6869-5p were significantly upregulated in both the 5-Gy and 10-Gy dose groups, showing a certain dose-response relationship. The RT-PCR results were consistent with the findings of high-throughput sequencing. In addition, the target genes of the differentially expressed miRNAs were mainly involved in RNA transcription and DNA damage. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these miRNAs participated in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Ras, mitogen-activated protein kinase (MAPK), and other signaling pathways. Conclusions: The expression of differential plasma miRNAs of radiotherapy patients was associated with irradiation injury and showed a certain dose-effect relationship. These differentially coexpressed plasma miRNAs could be used as an early indicator for estimating radiation injury.

The Clinical Efficacy of High-Voltage Long-Duration Pulsed Radiofrequency Treatment in Pudendal Neuralgia: A Retrospective Study.

BACKGROUND: Patients with pudendal neuralgia (PN) experience long-lasting chronic pain, hyperalgesia, and comorbid emotional disorders, such as depression and anxiety. Treatment via conventional pulsed radiofrequency (PRF) current carries a significantly high rate of failure. OBJECTIVE: To determine the safety and clinical efficacy of high-voltage, long-duration PRF application to the pudendal nerve in patients with PN. STUDY DESIGN: Observational retrospective design, self before-after controlled clinical trial. MATERIALS AND METHODS: We analyzed the records of 70 patients of our hospital with diagnosed PN. Treatment consisted of PRF application to the pudendal nerve, using computed tomography guidance to target the pudendal nerve at the level of the ischial spine or ischial tuberosity of the affected side. PRF was applied with the following parameters: temperature 42 °C, frequency 2 Hz, pulse width 20 ms, field intensity ramped gradually from 40 to 90 V, duration 900 sec. The therapeutic effect was evaluated by collecting patient scores for the visual analog scale (VAS), SF-36 health survey questionnaire (SF-36), and patient health questionnaire (PHQ-9) before treatment and at 1-, 4-, and 12-week follow-ups after PRF treatment. Data were analyzed by paired t-test with p < 0.05 considered to be statistically significant. RESULTS: VAS, SF-36, and PHQ-9 scores at 1, 4, and 12 weeks after high-voltage long-duration PRF treatment were significantly improved relative to their respective pretreatment baseline scores (p < 0.05 for all). The effective rate at 12 weeks after high-voltage long-duration PRF was up to 88.6%. LIMITATIONS: A small sample size and lack of a control group. CONCLUSIONS: High-voltage long-duration PRF provided significant short-term (at least 12 weeks) pain relief to most patients with PN; it also improved subjective measures of depression and quality of life over the same duration of time.

Laminaria japonica hydrolysate promotes fucoxanthin accumulation in Phaeodactylum tricornutum.

Fucoxanthin (Fx) has gained a growing attention due to the remarkable biological activities. The limited biomass of was the restrictive factor for Fx production in Phaeodactylum tricornutum. In this study, Laminaria japonica hydrolysate (LPH) with a low addition proportion of 1.5 ml/L, was proved to promote fucoxanthin accumulation and cell growth simultaneously. Fx topped at 27.9 mg/L after 10-d cultivation in the LPH group, with a biomass of 1.59 g/L and a Fx content of 17.55 mg/g. Three key plant hormones in LPH were screened responsible for promoting fucoxanthin accumulation. Transcriptomic analysis and qRT-PCR results showed that genes related to Fx formation were generally up- regulated. The study demonstrated that LPH addition was a feasible and efficient strategy to enhance production of fucoxanthin, facilitating the scale-up production of Fx in autotrophic culture.

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model.

OBJECTIVE: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish. METHODS: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 µmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio. RESULTS: According to the Chinese Pharmacopoeia (2015), ß-ecdysone (ß-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of ß-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 µmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 µmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and ß-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1. CONCLUSION: RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Application Progress and Prospect of Herbal and Western Medicine Combined with Antiplatelet Therapy for Cardiovascular Events.

Antiplatelet therapy is the key point in the treatment of cardiovascular and cerebrovascular diseases. Effective and safe antiplatelet therapy can avoid the risk of thrombosis or bleeding again. Herbal and Western medicine combined with antiplatelet therapy for ischemic cardiovascular events is a common phenomenon in clinical application, and more and more animal experiments, in vitro cell experiments, and randomized controlled clinical studies have also clarified the efficacy and interaction mechanism of the combination and safety. Herbal and Western medicine combined with antiplatelet therapy has made some progress in improving aspirin resistance and clopidogrel resistance, enhancing antiplatelet and antithrombotic effect, and reducing gastrointestinal adverse reactions caused by antiplatelet drugs. Both of them play the role of antiplatelet and antithrombotic by reducing platelet adhesion, inhibiting platelet activation and aggregation, and inhibiting platelet release, and the combination of drugs is safe. This article elaborates and analyzes the application progress and prospect of Chinese and Western medicine combined with antiplatelet therapy, in order to provide more theoretical support for future research.

Optimization design of curved outrigger structure based on buckling analysis and multi-island genetic algorithm.

In the present work, the working state of the crane leg is analyzed and discussed, and its structure is optimized. SolidWorks software is used for modeling; ANSYS software is used for finite element analysis. First of all, the constrained finite element method (CFEM) is used to analyze the linear eigenvalue buckling and geometric nonlinear buckling of outriggers with different cross-section shapes. Prove that the curved leg has certain advantages in buckling. At the same time, analyzing the leg along a different path of buckling condition and stress changes provide the basis for the design of the subsequent reinforcement. After selecting the best cross-section shape of the outrigger, the agent-based multi-island genetic algorithm is used to optimize the structural parameters of the outrigger under the transverse stiffened plate reinforced structure and the longitudinally stiffened plate reinforced structure respectively. It is proved that the outrigger with the transverse stiffened plate has a significant effect in improving the bearing capacity and in the lightweight of the structure. Finally, the gap between the movable leg and the fixed leg was changed, the stress of different gaps was analyzed by using the finite element method, and the appropriate gap value was selected according to the high-order fitting curve.

Panax quinquefolium saponin Optimizes Energy Homeostasis by Modulating AMPK-Activated Metabolic Pathways in Hypoxia-Reperfusion Induced Cardiomyocytes.

OBJECTIVE: To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. METHODS: The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. RESULTS: PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05). CONCLUSION: PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.

Antidepressant-like effects of albiflorin involved the NO signaling pathway in rats model of chronic restraint stress.

The depressant-like effects of albiflorin (AF) were studied on stressed chronic restraint stress (CRS) rats. Experimental rats were subjected to immobilization stress for a daily 6 h-restraining in a plastic restrainer for continuous 21 d and were treated with 30 or 15 mg·kg-1 of AF for 21 d. Control rats were maintained in completely non stressed conditions. Behavioral tests and biochemical analysis were applied to investigating a regulatory mechanism of anti-stress of AF. Treatment with AF significantly restored the depressant-like behaviors. Besides, AF increased the levels of 5-hydroxytryptophan (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NE) and dopamine (DA) in the hippocampus and increased the level of brain-derived neurotrophic factor (BDNF) in serum and protein expression in hippocampus. In addition, AF decreased the levels of hypothalamo-pituitary-adrenal (HPA) cascade, reduced the level of NO and cGMP in serum and inhibited the overexpression of 5-HT2AR mRNA and protein expression. Taken together, AF can modulate the NO-mediated network pathway in the hippocampus against stress-induced depressive-like behaviors. These physiological and behavioral changes allow rats to avoid potential deleterious effects of stress that may result from chronically elevated levels of glucocorticosteroids over days.