Baicalin reduces chronic stress-induced breast cancer metastasis via directly targeting b2-adrenergic receptor

Recent studies have shown that stress can substantially facilitate breast cancer metastasis,which can be reduced by nonselective β1/β2-adrenergic receptor(β1/β2-AR)blocker.However,several side effects were identified.Thus,it is extremely warranted to explore more effective and better-tolerated β2-AR blocker.Currently,we demonstrated that baicalin(BA),a major bioactive component of Scutellaria baicalensis Georgi,could significantly attenuate stress hormones especially epinephrine(Epi)-induced breast cancer cell migration and invasion in vitro.Mechanistically,we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability(DARTS)combined with mass spectrum assay,and BA photoaffinity probe with pull-down assay,which was further confirmed by a couple of biophysical and biochemical assays.Furthermore,we demonstrated that BA could directly bind to the Phe193 and Phe-289 of β2-AR,subsequently inhibit cyclic adenosine monophosphate-protein kinase A-focal adhesion kinase(cAMP-PKA-FAK)pathway,and thus impede epithelial-mesenchymal transition(EMT),thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model.These findings firstly identify BA as a potential b2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

Hippocampal HMGB1/TLR4 Pathway Mediates Cognitive Dysfunction in Chronic Stress Mice

Objective Chronic stress can induce cognitive dysfunction,but the underlying mechanisms remain unknown.Studies have confirmed that the high mobility group box 1/Toll-like receptor 4(HMGB1/TLR4)pathway is closely associated with cognitive impairment.Therefore,this research aimed to explore whether the HMGB1/TLR4 pathway involves in chronic stress-induced cognitive dysfunction.Methods The chronic unpredictable mild stress(CUMS)mouse model was established by randomly giving different types of stress every day for four consecutive weeks.Cognitive function was detected by novel object recognition test,Y-maze test,and Morris water maze test.The protein expressions of HMGB1,TLR4,B-cell lymphoma 2(BCL2),and BCL2 associated X(BAX)were determined by Western blot.The damage of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin(HE)staining.Results The protein expressions of HMGB1 and TLR4 were significantly increased in the hippocampus of chronic stress mice.Furthermore,inhibition of the HMGB1/TLR4 pathway induced by ethyl pyruvate(EP,a specific inhibitor of HMGB1)and TAK242(a selective inhibitor of TLR4)treatment attenuated cognitive impairment in chronic stress mice,according to the novel object recognition test,Y-maze test,and Morris water maze test.In addition,administration of EP and TAK242 also mitigated the increase of apoptosis in the hippocampus of chronic stress mice.Conclusion These results indicate that the hippocampal HMGB1/TLR4 pathway contributes to chronic stress-induced apoptosis and cognitive dysfunction.

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Periodontitis and chronic kidney disease:A bidirectional relationship based on inflammation and oxidative stress

Chronic kidney disease(CKD)and chronic periodontitis(CP)are prevalent conditions which significantly impact public health worldwide.Both diseases share inflammatory and oxidative stress mechanisms,an indication of a likely bidirectional relationship.This editorial explored the association between CKD and CP by highlighting common inflammatory mechanisms and recent research findings that address this interrelationship.Through reviews of recent studies,we discussed how periodontal bacteria may activate systemic immune responses that affect both periodontal and renal tissues.Additionally,meta-analysis data indicated an increased risk of CKD development in patients with CP,and vice versa.The results suggest the need for more rigorous research in the future in order to address the confounding factors and evaluate specific periodontal health interventions and their direct effects on kidney function.We emphasized the importance of comprehensive and multidisciplinary care for the improvement of the overall health of patients affected by CP and CKD.

Effects of Intermittent Hypoxia Exposure on Symptoms of Chronic Fatigue Syndrome in Repeated Restraint Stress and Forced Swimming Induced-Mouse Model

Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermittent hypoxia, consisting of alternating exposure to hypoxia and normoxia, plays a very important role in improving CFS. However, the essential components for improving learning and memory in CFS patients as well as their mechanism are largely unknown. Objectives: This study aims to analyze the effects of 12% and 15% hypoxia on the expression of alpha tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB) in CFS induced-mouse model for clarifying the effects on the learning and memory function. Methods: A total of 48 type IC mice were used. The CFS mouse model was established using restrained stress and repeated forced swimming. Treatment of CFS was done by exposing CFS mice to intermittent hypoxia at 12% and 15%. The effects of intermittent hypoxia on learning and memory as well as its mechanism of action on inflammation were tested respectively with the Morris test, the SDS page, the immunohistochemistry technique and the Nissl staining. Results: We found that 12% and 15% intermittent hypoxia exposure improved learning capacity and memory of CFS induced-mice. SDS page showed that CFS caused higher TNF-α expression. By exposing CFS mice to 12% and 15% intermittent hypoxia, TNF-α expression decreased significantly, with a much better effect at 15%. Both TNF-α and NF-κB increased in CFS state and decreased after treatment with intermittent hypoxia. Conclusion: Intermittent hypoxia improves learning capacity and memory. It acted by decreasing NF-κB come to down-regulating TNF-α and ameliorates learning capacity and memory impairment in CFS mice.

Antidepressant effects of Yuanzhi (Polygalae Radix) extract on chronic unpredictable mild stress-induced depression in rats: modulation of the NLRP3 inflammasome and NF-κB pathway

Objective To investigate the antidepressant effects of Yuanzhi(Polygalae Radix;PR)aqueous extract on chronic unpredictable mild stress(CUMS)-induced depression rat models and the underlying mechanisms.Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control;model;low dose of PR(PR-L;0.5 g/kg);high dose of PR(PR-H;1 g/kg);and fluoxetine(10 mg/kg)groups;with 8 rats in each group.Except for the rats in control group;those in the other four groups underwent CUMS-induced depression modeling.PR and fluoxetine were administered intragastrically once daily;30 min prior to the CUMS procedure;for 14 consecu-tive days until the behavioral tests were performed.After CUMS modeling;the sucrose prefer-ence test(SPT);open field test(OFT);novelty-suppressed feeding test(NSFT);forced swim test(FST);and tail suspension test(TST)were employed to assess the pharmacological ef-fects of PR on the mitigation of depressive-like behaviors in rat models.Additionally;the en-zyme-linked immunosorbent assay(ELISA)was utilized to quantify the serum levels of tumor necrosis factor(TNF)-α;interleukin(IL)-6;and IL-1βin the rats.Western blot analysis was al-so conducted to evaluate the protein expression levels of nuclear factor kappa-B(NF-κB);in-ducible nitric oxide synthase(iNOS);cyclooxygenase-2(COX-2);nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain containing 3(NLRP3);apoptosis-associated speck-like protein containing caspase recruitment domain(ASC);and caspase-1 in the hippocampal tissues of the rats.Immunofluorescence staining was per-formed to observe the morphological changes in ionized calcium-binding adapter molecule 1 positive(Iba-1+)cells in the dentate gyrus(DG)of rats with CUMS-induced depression.Results(i)Treatment with PR-H and fluoxetine resulted in significant enhancements in both the total distance and time the rats moved during tests(P<0.01 and P<0.05;respectively).Post-administration of PR-H and fluoxetine also led to statistically significant increase in su-crose preference among rats(P<0.05).Besides;PR-L;PR-H;and fluoxetine treatment markedly decreased the latency of ingestion(P<0.05;P<0.05;and P<0.01;respectively).As observed from the FST;PR-L;PR-H;and fluoxetine presented antidepressant effects on rats with CUMS-induced depression;leading to the reduction in time of their immobility(P<0.05;P<0.01;and P<0.01;respectively).The results of TST indicated reduced immobility time in rats receiving PR-H and fluoxetine treatment as well(P<0.01).(ii)Rats in model group showed an increase in the levels of Iba-1+microglia in their left and right brains in compari-son with control group(P<0.01).However;such increase was negated post PR treatment(P<0.01).Treatment with PR-L;PR-H;and fluoxetine considerably reduced the levels of inflam-matory factors(TNF-α;IL-1β;and IL-6;P<0.01).In addition;treatment of PR-L and PR-H ef-fectively counteracted the elevated levels of NLRP3;ASC;and caspase-1;and markedly down-regulated the expression levels of phosphorylated p65(p-p65);COX-2;and iNOS in rats’hip-pocampus(P<0.01).Conclusion Collectively;these findings indicate that PR exerts an antidepressant effect on rats with CUMS-induced depression partially through the modulation of the NLRP3 and NF-κB signaling pathways.

Depression and anxiety,peripheral blood inflammatory factors,and stress levels on therapeutic outcomes in patients with chronic wounds

BACKGROUND The incidence of chronic wounds is rising due to an aging population and lifestyle changes in our country.In addition,as the disease spectrum evolves,chronic wounds have become common clinical issues that seriously threaten health and impose significant social and economic burdens.AIM To investigate how depression,anxiety,peripheral blood inflammatory factors,and stress levels affect therapeutic outcomes in patients with chronic wounds.METHODS Retrospectively collected clinical data from 110 patients with chronic wounds treated at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)between January 2021 and December 2023,categorizing them into effective and ineffective groups based on treatment effects.Differences between both groups were analyzed using univariate analysis,independent risk factors identified via logistic regression,and their predictive value assessed through receiver operating characteristic analysis.RESULTS Following treatment,95 cases were classified as the effective group(cured or improved),while 15 cases with improvement formed the ineffective group.Significant differences between both groups were noted in wound area,infection status,daily bed time,Hamilton Anxiety Rating Scale(HAMA)scores,Hamilton Depression Rating Scale(HAMD)scores,and levels of interleukin-6,tumor necrosis factor-alpha,and superoxide dismutase(P<0.05).Logistic regression analysis identified a wound area≥7 cm^(2),HAMA≥9 scores,and HAMD≥8 scores were independent risk factors for ineffective treatment in patients with chronic wounds(P<0.05).The receiver operating characteristic curve analysis revealed that the area under the curve for ineffective treatment based on wound area,HAMA,and HAMD was 0.767,0.805,and 0.768 respectively.CONCLUSION Wound size,anxiety,and depression are significant factors influencing the therapeutic outcomes in patients with chronic wounds that require careful attention,alongside the development of appropriate strategies.

Pilot study on the effect of flavonoids on arterial stiffness and oxidative stress in chronic kidney disease

BACKGROUND Flavonoids,the main class of polyphenols,exhibit antioxidant and antihypertensive properties.AIM To prospectively investigate the impact of flavonoids on arterial stiffness in patients with chronic kidney disease(CKD)stagesⅠ-Ⅳ.METHODS In this prospective,single-arm study,CKD patients with arterial hypertension and diabetes mellitus were enrolled.Baseline demographic,clinical,and laboratory variables were recorded.Patients received daily treatment with a phenol-rich dietary supplement for 3 months.Blood pressure,arterial stiffness(carotidfemoral pulse wave velocity,central pulse pressure),and oxidative stress markers(protein carbonyls,total phenolic compound,total antioxidant capacity)were measured at baseline and at study end.RESULTS Sixteen patients(mean age:62.5 years,87.5%male)completed the study.Following intervention,peripheral systolic blood pressure decreased significantly by 14 mmHg(P<0.001).Carotid-femoral pulse wave velocity decreased from 8.9 m/s(baseline)to 8.2 m/s(study end)(P<0.001),and central pulse pressure improved from 59 mmHg to 48 mmHg(P=0.003).Flavonoids also reduced oxidative stress markers including protein carbonyls(P<0.001),total phenolic compound(P=0.001),and total antioxidant capacity(P=0.013).CONCLUSION Flavonoid supplementation in CKD patients shows promise in improving blood pressure,arterial stiffness,and oxidative stress markers.

Jobelyn^(■), a Sorghum-Based Nutritional Supplement Attenuates Unpredictable Chronic Mild Stress-Induced Memory Deficits in Mice

The ability of an organism to adapt to aversive stressful situations or life challenging circumstances is very crucial to its state of health and survival. However, breakdown in adaptation due to persistent uncontrollable stress, leads to impairment of bodily functions and onset of a variety of pathological disorders especially memory decline. This study was designed to evaluate the effect of Jobelyn&reg;(JB), a potent antioxidant sorghum-based food supplement on unpredictable chronic mild stress (UCMS)-induced memory impairment in mice. Male Swiss mice were given JB (5 - 50 mg/kg, p.o) 30 min prior to exposure to UCMS for 14 consecutive days before testing for memory. Thereafter, the serum corticosterone level was estimated by using ELISA kits. The levels of malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase activity were estimated in the brain homogenate using spectrophotometer. Histology of the brain tissues and estimation of the populations of viable neurons in the hippocampal region were done after staining with hematoxyline and eosin. Our results showed that JB reversed memory impairment and suppressed corticosterone concentrations induced by UCMS. Moreover, JB reduced oxidative stress in the brain of UCMS-mice as shown by decreased MDA levels and elevated GSH concentrations. It also decreased brain acetylcholinesterase activity when compared with chronic stress group (p < 0.05). Furthermore, JB (5 - 10 mg/kg, p.o) offered significant protection against UCMS-induced degeneration and death of neuronal cells of the cornu ammonis 3 (CA3) of the hippocampal region of the brain indicating neuroprotection. Taken together, these findings suggest that JB attenuates memory deficits induced by UCMS in mice and may be useful therapeutically for stress-related cognitive dysfunctions. The reduction in the levels of serum corticosterone, antioxidation, neuroprotection and inhibition of cholinesterase enzyme might be contributing significantly to the positive effect of JB on memory in mice exposed to unpredictable chronic mild stress.

Octreotide ameliorates gastric lesions in chronically mild stressed rats

AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for CMS.Octreotide was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress procedure.Macro-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed histopathologically.Moreover,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,P<0.001),prostaglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose levels.These beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.

Alterations in intestinal microbiota composition coincide with impaired intestinal morphology and dysfunctional ileal immune response in growing-finishing pigs under constant chronic heat stress

Background:Previous studies had shown that short-term acute heat stress(HS)affected the host’s metabolism and intestinal microbiota independent of feed intake(FI)reduction,and long-term calorie restriction caused intestinal morphological injuries and gut microbial alterations.However,research on the effects of constant chronic HS on intestinal microbial composition and the roles of FI reduction played in is limited.This study aimed to investigate the effects of 7-day constant chronic HS on the composition of intestinal microbes in growing-finishing pigs,and its relationship with pigs’performance,intestinal morphology,and ileal immune response.Twenty-four growingfinishing pigs(Duroc×Large White×Landrace,30±1 kg body weight)were randomly assigned to three treatments(n=8),1)thermal neutral(TN)conditions(25±1℃)with ad libitum FI,2)HS conditions(35±1℃)with ad libitum FI,3)pair-fed(PF)with HS under TN conditions to discriminate the confounding effects of dissimilar FI,and the FI was the previous day’s average FI of HS.The small intestinal segments(duodenum,jejunum,and ileum)and feces were collected on d 8.Results:Results indicated that HS drastically declined(P<0.05)average daily gain(ADG)and average daily feed intake(ADFI)(about 61%)in comparison with TN,and caused hyperpyrexia,meanwhile PF caused hypothermia.Morphological observation by light and electron microscopes showed that both HS and PF treatment decreased(P<0.05)the villus and microvillus height compared with TN.Additionally,HS increased(P<0.05)protein expression of heat shock protein 70 in the duodenum,jejunum,and ileum.Furthermore,the expression of tight junction protein zonula occluden-1(ZO-1)in the duodenum and ileum,and Occludin in the ileum were enhanced(P<0.05)compared with TN and PF.Moreover,HS significantly enhanced(P<0.05)the mRNA relative expression of inflammatory cytokines(TLR-2,TLR-4,and tumor necrosis factor-α(TNF-α),IL-6,IL-8,PG1–5,β-defensin 2(pBD-2)),mucins(mucin-1 and mucin-2)and P65 protein level in the ileal mucosa tissue.Intestinal microbiota analysis by 16S rRNA sequencing showed lower(P<0.10)αdiversity in both HS and PF,and a separated cluster ofβdiversity among groups.Compared with TN,HS but not PF mainly reduced(FDR<0.05)Bacteroidetes(phylum),Bacteroidia(class)and elevated the proportions of Proteobacteria(phylum,FDR<0.05),Bacillales(order,FDR<0.05),Planococcaceae(family,FDR<0.05),Kurthia(genus,FDR<0.05),Streptococcaceae(family,FDR<0.10)and Streptococcus(genus,FDR<0.10).Notably,Lactobacillales(order)was decreased(FDR<0.05)by PF alone.Furthermore,the Spearman correlation analysis indicated that the microbes prevalent in HS were positively(P<0.05)associated with intestinal morphological injuries indicators and ileal immune response parameters,and the microbes reduced in HS were negatively(P<0.05)with the performance data.Conclusions:Intestinal morphological injuries and ileal immune response caused by constant chronic HS independent of FI showed close connections with alterations in intestinal microbiota in growing-finishing pigs.

Oxidative Stress before and after Operation in Patients with Chronic Cholecystitis Containing Gallstone

To study the relationship of oxidative, antioxidative constituents and antioxidases in blood with chronic cholecystitis containing gallstone, levels of lipoperoxides (LPO), nitric oxide (NO), vitamin C(VC), vitamin E (VE) and β carotene (β CAR) in plasma as well as level of LPO, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH Px) in erythrocytes were investigated by spectrophotometric assay in 107 patients with this condition (PCg) and 100 healthy volunteers (HVs). Compared with HVs group, the average value of LPO and NO in plasma and that of LPO in erythrocytes of PCg group were significantly increased ( P <0.0001), while that of VC, VE and β CAR in plasma and the average activities of SOD, CAT and GSH Px in erythrocytes were significantly decreased ( P <0.0001). Linear regression and correlation analysis for 107 preoperative PCg showed that the value of LPO and NO in plasma and that of LPO in erythrocytes of PCg gradually increased ( P <0.0001), representing a significant linear positive correlation. The value of VC, VE and β CAR in plasma and that of SOD, CAT and GSH Px in erythrocytes of PCg gradually decreased ( P <0.0001), representing a significant linear negative correlation. Stepwise regression and correlation analysis for 107 preoperative PCg suggested that the closest correlation was observed between the course of disease and the value of NO and VC in plasma and that of SOD, GSH Px and LPO in erythrocytes, r =0.7306, F =32.1408, P <0.0001. Compared with the preoperative PCg group, the average value of LPO and NO in plasma and that of LPO in erythrocytes of the postoperative PCg group were significantly decreased ( P <0.0001). Furthermore, the average value of VC in plasma and that of SOD, CAT and GSH Px in erythrocytes of the postoperative PCg group were significantly increased ( P <0.0001), whereas no significant difference was found between their average value of VE and β CAR in plasma. These findings suggested that oxidative stress was an aggravating pathological condition in PCg group. Therefore, we recommend that in treating PCg, antioxidants such as VC, VE, β CAR should be given in order to alleviate their potential oxidative damages.

Hippocampal activation of c-Jun N-terminal kinase,protein kinase B,and p38 mitogen-activated protein kinase in a chronic stress rat model of depression

Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase （JNK）, protein kinase B （Akt）, and p38 mitogen-activated protein kinase （p38） signal transduction pathway, and also regulate various apoptotic cascades. JNK and p38 promote apoptosis, but Akt protects against apoptosis, in hippocampal neurons. However, changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood. Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group （P 〈 0.05）. No significant difference in JNK phosphorylation levels was detected in the rat cerebral cortex between stress and control groups, and no significant difference in Akt and p38 phosphorylation levels was detected in the rat hippocampus and cerebral cortex between stress and control groups （P 〉 0.05）. These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.

Electroacupuncture pretreatment exhibits antidepressive effects by regulating hippocampal proteomics in rats with chronic restraint stress

The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui（GV20） and Yintang（GV29） acupoints was performed daily（1 m A, 2 Hz, discontinuous wave, 20 minutes） prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins（COG） database. Twenty-seven differential proteins（uncharacteristic proteins expected） were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins exist in nerve cells.

Antidepressant-like Effects of Ginsenoside Rg1 in the Chronic Restraint Stress-induced Rat Model

Objective To investigate the ameliorating effect of ginsenoside Rg1 on the depression-like behaviors induced by chronic restraint stress(CRS)in rats and the underlying mechanisms.Methods Forty male Wistar rats were divided into 4 groups according to their baseline sucrose preference:control group,model group,and Rg1-treated groups(5 and 10 mg/kg).Except for control group,the groups were exposed to CRS(6 h/day)for 28 days.All drugs were intraperitoneally administered once daily to CRS rats after restraint stress for 14 days.The behavioral tests were carried out via the open field test(OFT),sucrose preference test(SPT),forced swim test(FST),and the Morris water maze(MWM)4 weeks following CRS induction.The levels of serum corticosterone(CORT)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the prefrontal cortex(PFC)were analyzed using commercial ELISA kits.The levels of the neurotransmitter(5-HT,5-HIAA,Ach,NE,GABA and Glu)in the PFC were measured by ultra-performance liquid chromatography tandem mass spectrometry.The protein expression of BDNF,Trkb,Bax and Bcl-2 in the PFC was detected by western blotting.Results Owing to increased sucrose consumption in the SPT,decreased immobility time in the FST,and the improved cognitive performance in MWM,chronic treatment with Ginsenoside Rg1 was found to significantly attenuate depressionlike behaviors(anhedonia,behavioral despair and poor spatial memory)in rats.Moreover,CRS exposure caused evident alterations in the levels of the neurotransmitters(5-HT,5-HIAA,Ach,GABA and Glu)and the activities of the antioxidant defense biomarkers(SOD,MDA and GSH-x)in the PFC and the levels of corticosterone in serum.However,Ginsenoside Rg1 treatment could restore these levels to normal values.Additionally,Ginsenoside Rg1 treatment significantly reverted the decreased expression of BDNF,Trkb and Bcl-2 and the increased expression of Bax in the PFC of CRS rats.Conclusions Ginsenoside Rg1 could attenuate the CRS-induced depression-like behaviors,in part,by regulating neurotransmitter levels and HPA function,antagonizing oxidative stress and apoptosis,and restoring BDNF-TrkB signaling in PFC.Altogether,our results provide a novel basis regarding the potential therapeutic effects of Rg1 on depression.

Antidepressant Effect of Shenwei Ningyu Tablets on Rat Chronic Stress Model and Mouse Tail Suspension Model

[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.

Comparative proteomic analysis of hippocampal proteins from chronic stressed rats

Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic

Increased oxidative stress and oxidative damage associated with chronic bacterial prostatitis

Aim： To investigate whether chronic bacterial prostatitis might increase oxidative stress and oxidative damage in chronic bacterial prostatitis patients （CBPP）, and to explore its possible mechanism. Methods： Enrolled in a casecontrol study were 70 randomly sampled CBPP and 70 randomly sampled healthy adult volunteers （HAV）, on whom plasma nitric oxide （NO）, vitamin C （VC）, vitamin E （VE） and β-carotene （β-CAR） level, erythrocyte malondialdehyde （MDA） level, as well as erythrocyte superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX） activities were determined by spectrophotometry. Results： Compared with the HAV group, values of plasma NO and erythrocyte MDA in the CBPP group were significantly increased （P 〈 0.001）; those of plasma VC, VE and β-CAR as well as erythrocyte SOD, CAT and GPX activities in the CBPP group were significantly decreased （P 〈 0.001）. Findings from partial correlation for the 70 CBPP showed that with prolonged course of disease, values of NO and MDA were gradually increased （P 〈 0.001）, and those of VC, VE, β-CAR, SOD, CAT and GPX were gradually decreased （P 〈 0.05- 0.001）. The findings from stepwise regression for the 70 CBPP suggested that the model was Y= -13.2077 ＋ 0.1894MDA ＋ 0.0415NO - 0.1999GPX, F = 18.2047, P 〈 0.001, r = 0.6729, P 〈 0.001. Conclusion： The findings suggest that there exist increased oxidative stress and oxidative damage induced by chronic bacterial prostatitis in the patients, and such phenomenon was closely related to the course of disease.

Dynamic changes of behaviors, dentate gyrus neurogenesis and hippocampal miR-124 expression in rats with depression induced by chronic unpredictable mild stress

The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.

Toxic stress,inflammation and symptomatology of chronic complications in diabetes

Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035.The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009.The effects of toxic stress,the culmination of biological and environmental interactions,on the development of diabetes complications is gaining attention.Stress impacts the hypothalamus-pituitaryadrenal axis and contributes to inflammation,a keybiological contributor to the pathogenesis of diabetes and its associated complications.This review provides an overview of common diabetic complications such as neuropathy,cognitive decline,depression,nephropathy and cardiovascular disease.The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes,associated symptomatology and importance of early identification of symptoms of depression,fatigue,exercise intolerance and pain.