TNF-αand IL-1β Research Articles

Association between neutrophil-to-lymphocyte ratio and motor subtypes in idiopathic Parkinson's disease: a prospective observational study.

Peripheral immunity and neuroinflammation interact with each other and they play important roles in the pathophysiology of idiopathic Parkinson's disease (IPD). There have been very few real-world reports on the relationship between peripheral immune inflammation and motor phenotypes of IPD. This study aimed to investigate the potential correlation between peripheral inflammatory indicators and motor subtypes in patients with IPD. This observational, prospective case-control study examined patients with IPD and healthy controls (HC) matched for age and sex between September 2021 and July 2023 at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University. The levels of peripheral inflammatory indicators were collected from each patient with IPD and HCs. Differences in the levels of peripheral inflammatory indicators among groups were compared. Binary logistic regression analysis was used to explore the inflammatory mechanism underlying the motor subtype of IPD. A total number of 94 patients with IPD were recruited at the Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University between September 2021 and July 2023, including 49 males and 45 females, and 37 healthy volunteers matched for age and sex were also enrolled as the control group. Of the 94 patients with IPD, 42.6% performed as the TD motor subtype and 57.4% performed as the AR motor subtype. NLR and the plasma levels of IL-1βand TNF-α in the IPD group were higher than those in the HC group (P < 0.05). The disease duration, Hoehn and Yahr (H-Y) stage, NLR, and the levels of IL-1β in the AR group were higher than those in the TD group (P < 0.05). Additionally, IL-1β plasma levels and NLR were positively correlated with disease duration, H-Y stage, movement disorder society-Unified Parkinson's Disease Rating Scale-III motor score, and AR subtype. The binary logistic regression model revealed that the plasma level of IL-1β was mildly associated with the AR motor subtype and NLR was strongly associated with the AR motor subtype. The combination of NLR and IL-1β showed better performance in identifying the AR motor subtype. NLR is strongly associated with the AR motor subtype in IPD, and peripheral immunity is probably involved in the pathogenesis of AR motor subtype in IPD.

Effects of Polyphenols and Lignans of Phyllanthus amarus Schumach. and Thonn. on IL-1β and TNF-α Secretions from LPS-induced THP-1-derived Macrophages

Background: Phyllanthus amarus exhibited immunosuppressive and anti-inflammatory effects in several in vitro and in vivo studies. However, there is no report on the inhibitory effects of its secondary metabolites on pro-inflammatory cytokines secretion from human THP-1-derived macrophages. background: Phyllanthus amarus exhibited immunosuppressive and anti-inflammatory effects in several in vitro and in vivo studies. However, there is no report on the inhibitory effects of its secondary metabolites on pro-inflammatory cytokines secretion from human THP-1-derived macrophages. Objective: The objective of this study was to correlate the polyphenols (ellagic acid (EA), gallic acid (GA), geraniin (GER), and corilagin (COR)) and lignans ((phyllanthin (PHY), hypophyllanthin (HYPO), niranthin (NIR), phyltetralin (PHYLT), and isolintetralin (ISO)) of 80% ethanol extract of P. amarus with their inhibitory effect against IL-1β and TNF-α secretions from LPS-induced THP-1- derived macrophages. Methods: Chemical profiling of P. amarus was carried out by LC-MS/MS analysis. Validated qualitative and quantitative reversed-phase HPLC analyses of the P. amarus extract were performed for the determination of lignan and polyphenol contents. Human THP-1-derived macrophages were prepared by treatment of THP-1 cells with phorbol 12-myristate 13-acetate (PMA). The inhibition of cytokines released by the extract, lignans and polyphenols in the cells was investigated using ELISA assay. method: Chemical profiling of P. amarus was carried out by LC-MS/MS analysis. Validated qualitative and quantitative reversed phase HPLC analyses of the P. amarus extract were performed for determination of lignan and polyphenol contents. Human THP-1 derived macrophages were prepared by treatment of THP-1 cells with phorbol 12-myristate 13-acetate (PMA). The inhibition of cytokines release by the extract, lignans and polyphenols in the cells were investigated using ELISA assay. Results: P. amarus extract and its chemical constituents significantly reduced the levels of IL-1β and TNF-α in a dose-dependent manner. At a dose of 50 μM, COR exhibited a maximum inhibition of 81.11% on TNF-α secretion, while GER showed 72.56% inhibition on IL-1β secretion. COR demonstrated the strongest inhibition of TNF-α secretion, exhibiting an IC50 value of 9.06 μM, which was comparable to that of dexamethasone (7.07 μM). Meanwhile, GER was the most potent against IL- 1β secretion, exhibiting an IC50 value of 20.09 μM. In the case of TNF-α secretion, the order of potency observed among the active compounds, with regard to IC50 value, was COR &gt; GER &gt; HYPO &gt; PHY &gt; NIR &gt; GA &gt; EA &gt;ISO &gt; PHYLT. For IL-1β secretion, the order of potency was GER &gt; NIR &gt; COR &gt; GA &gt; EA &gt; PHY &gt; HYPO &gt; PHYLT &gt; 1SO. Conclusion: The polyphenol contents of P. amarus, especially COR and GER, contributed significantly to the suppression of cytokines secretion, and they have the potential to be developed into agents for the treatment of pathologic inflammation.

Short-term immunotoxicity induced by florpyrauxifen-benzyl herbicide exposure in the spleen of male albino mice.

Florpyrauxifen-benzyl (FPB)is a new arylpicolinate systemic herbicide that has been used to control or suppress the majority of herbicide-resistant biotype weeds in rice. To our knowledge, the impact of FPB on the immune system remains undetected thus far. Hence, this work aimed to address the toxic effects of FPB and the possible related mechanisms on the spleen of exposed mice. Initially, an acute toxicological test was performed to ascertain the median lethal dose (LD50) of FPB for 24 h which was found to be 371.54 mg/kg b.wt. For mechanistic evaluation of FPB toxicity, three sublethal doses (1/20th, 1/10th, and 1/5thLD50) were orally administered to mice for 21 consecutive days. Changes in spleen relative weight, oxidative status, apoptotic and inflammatory markers, histopathological alterations were evaluated. Following the FPB exposure, significant (p < 0.05) decline in spleen index, apoptotic features, histolopathological changes were observed. Additionally, excessive oxidative stress in spleen tissues was monitored by downregulating antioxidant enzymes and upregulating the oxidant parameters. Furthermore, exposure to FPB resulted in notable activation of the NF-қB signaling pathway, accompanied by elevated levels of pro-inflammatory cytokines (namely, IL-1βand TNF-α)as well as CD3 and CD19 levels have decreased significantly in spleen tissues. Collectively, FPB exposure exhibited apoptosis, oxidative stress, immunosuppression, and inflammatory response in a dose-dependent manner, leading to spleen tissue damage and immunotoxicity. Further studies on FPB is recommended to outstand its hazards on ecosystems.

Dynamic m6 A profiles reveal the role of YTHDC2-TLR2 signaling axis in Talaromyces marneffei infection.

Talaromyces marneffei (TM) immune evasion is an important factor leading to the high mortality rate of Penicilliosis marneffei. N6 -methyladenosine (m6 A) plays important roles in host immune response to various pathogen infections, yet its role in TM and HIV/TM coinfection remains largely unexplored. Here we reported genome-wide transcriptional m6 A profiles of TM mono-infection and HIV/TM coinfection. Our finding revealed dynamic alterations in global m6 A levels and upregulation of the m6 A reader YTH N6 -methyladenosine RNA binding protein C2(YTHDC2) in TM-infected macrophages. Knockdown of YTHDC2 in TM-infected cells showed an elevated expression of TLR2 through m6 A-dependence, along with upregulation of TNF-αand IL1-β. Overall, we characterized the m6 A profiles of the host and fungus before and after TM infection, and demonstrated that YTHDC2 mediates the key m6 A site of TLR2 to exert its function. These findings provide new insights into the underlying mechanisms and novel therapeutic approaches for TM diseases.

Comparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence

Osteoarthritis (OA) is an age-related degenerative joint disease that causes progressive cartilage loss. Chondrocyte senescence is a fundamental mechanism that contributes to the imbalance of matrix homeostasis in OA by inducing senescence-associated secretory phenotype (SASP). Although OA chondrocytes are mainly exposed to oxidative and inflammatory stresses, the role of these individual stresses in chondrocyte senescence remains unclear. In this study, we compared the effects of these stresses on the senescence of rat chondrocytes. Rat chondrocytes were treated with H2O2 and a combination of IL-1β and TNF-α (IL/TNF) to compare their in vitro effect on senescent phenotypes. For in vivo evaluation, H2O2 and IL/TNF were injected into rat knee joints for 4 weeks. The in vitro results showed that H2O2 treatment increased reactive oxygen species, γ-H2AX, and p21 levels, stopped cell proliferation, and decreased glycosaminoglycan (GAG)-producing ability. In contrast, IL/TNF increased the expression of p16 and SASP factors, resulting in increased GAG degradation. Intraarticular injections of H2O2 did not cause any changes in senescent markers; however, IL/TNF injections reduced safranin O staining and increased the proportion of p16- and SASP factor-positive chondrocytes. Our results indicate that oxidative and inflammatory stresses have significantly different effects on the senescence of rat chondrocytes.

Safety Assessments of Electroacupuncture-Mediated Blood–Brain Barrier Opening: An Animal Study

The presence of the Blood–Brain barrier (BBB) makes it difficult for therapeutic agents to reach the brain to treat brain diseases. As an emerging treatment, electroacupuncture (EA)-mediated BBB opening can temporarily increase the permeability of the brain blood vessels to increase the concentration of the therapeutic agent in the brain parenchyma, which offers great clinical benefits. Recent studies have suggested that BBB opening with excessive exposure levels may cause tissue/cell damage and short-term behavioral changes. Here, we investigated whether the EA-mediated BBB opening cause serious adverse events in the normal rat brain tissue and motor behavior, such as brain tissue damage, histopathologic alteration, or aggravated behavioral changes. EA was performed on the accupoint GV26 and GV20. Evans Blue Assay (EBA) and fluorescein isothiocyanate (FITC)–dextran Assay were performed to assess the BBB permeability. Immunofluorescence of GFAP-positive cells was marked and Hematoxylin-eosin (HE) Staining was carried out for assessing brain cortex damage. Tunel Assay was conducted to assess cell apoptosis. ELISA was used to measure the contents of TNF-α and IL-1β in brain tissue to explore the inflammatory response. The open field test, balance beam test and Y-Maze test were carried out to assess and neural behaviour. EA can induce an increase in BBB permeability on rats, allowing the macromolecular tracer Evans blue (EB) and Fluorescein Isothiocyanate (FITC)–Dextran to enter the brain. Histological analysis indicated that there was no obvious red blood cell leakage and a cellular apoptotic response in the brain tissue of rats with EA treatment. In addition, EA stimulation at specific parameters did not impair the rats’ motor ability, balance and coordination, and short-term spatial learning and memory. Our results suggest that EA can safely and effectively open the BBB in rats without causing brain damage and behavioral memory impairment.

Effect Of Baduanjin On Serum Inflammatory Factorsin Female College Students With Primary Dysmenorrhea

PURPOSE: Dysmenorrhea is the most common gynecological disorder in young women. In China, the overall prevalence of dysmenorrhea was increased from 69.30%(2011) to 80.40%(2018) in female college students. There were no gold standards for the treatment of primary dysmenorrhea. This study aimed to examine the effects of Baduanjin on serum inflammatory factors changes in female college students with primary dysmenorrhea, and to explore its intervention effects. METHODS: 16 female college students with primary dysmenorrhea were recruited and randomly divided into the exercise group(EG:20 ± 2 yrs) and the control group(CG:20 ± 1 yrs). Buduanjin intervention lasted 3menstrual cycles with the frequency of 3 days per week and 3 times each day. The serum PGF2α, IL-1βand TNF-α, the visual analog scales(VAS) score and dysmenorhea symptom score were analyzed at baseline, 12 weeks after intervention. Comparisons from before to after the serum inflammatory factors, VAS score and the dysmenorhea symptom score of CG and EG were performed separetely by using T test. RESULTS: The total effective rate of dysmenorrhea improvement was 87.50% in EG, which is significant higher than CG(87.50% vs. 12.50%, P < 0.05). After the intervention, PGF2αwas significantly reduced in the EG(128.27 ± 23.24 vs.72.61 ± 17.43 pg/ml, P < 0.05), as well as the IL-1β in EG (60.88 ± 14.84 vs.33.88 ± 11.36 pg/ml, P < 0.05). The VAS score and dysmenorhea symptom score were significantly higher compared with the baseline (VAS score: 6 ± 2 vs.4 ± 1,P < 0.05; dysmenorhea symptom score: 11 ± 3 vs.5 ± 1, P < 0.05). Though the concentration of TNF-α in the EG had the decreased trend, there was no statistically significant difference when compared with baseline (32.33 ± 7.73 vs.26.78 ± 6.32 pg/ml, P > 0.05). As for CG, there were no significant decreased for all inflammatory factors and scores. All participants in the EG reported that they were aware of the benefits of Baduanjin and that this helped in the management of pain after exercise treatment. CONCLUSIONS: Baduanjin is a safe and effective intervention for women to reduce the severity of dysmenorrhea. 3 menstrual cycles of Baduanjin exercise intervention can reduce the serum inflammatory factors and relieve the pain of primary dysmenorrhea in female college students.Supported by Beijing Sport University X202110043024.

Effect of Thymosin β4 on Deep Second-Degree Scald Wound Healing in Rats via Wnt/β-Catenin Pathway

&lt;sec&gt; &lt;title&gt;Objective:&lt;/title&gt; The purpose of this research is to explore the influences of thymosin β4 (Tβ4) in deepsecond-degree scald wound healing of rat skin and its relationship with Wnt/β-catenin pathway. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Methods:&lt;/title&gt; Deep second-degree scalded model rats were prepared and divided into normal saline (NS) treatment group, Tβ4 treatment group and FH535 inhibitor group. Then, the concentrations of inflammatory factors in the rats were monitored via adopting the correlated TNF-α and IL-1β ELISA kits. In the meantime, the wound healing rate was analyzed via photography. Subsequently, the qRTPCR procedure was wielded to determine Wnt1 and β-catenin expression in wound tissues, and the degree of wound tissue injury was examined via hematoxylin and eosin (HE) staining. Finally, Western blotting (WB) was adopted to assess Wnt/β-catenin pathway-associated protein levels. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Results:&lt;/title&gt; Releasing amount of TNF-α and IL-1β were conspicuously up-regulated after scalding (p &lt;0.01), and Wnt1 and β-catenin expression at molecular transcription level was also significantly raised (p &lt; 0.01). Besides, treatment with 18 μg of Tβ4 significantly increased the wound healing rate of scalded rats (p &lt; 0.01). In addition, Tβ4 treatment significantly promoted wound healing (p &lt; 0.01) and increased the Wnt1 and β-catenin expression levels (p &lt; 0.01). Moreover, FH535 significantly restrained the Wnt/β-catenin pathway-correlated protein levels (p &lt; 0.01) and wound healing. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Conclusion:&lt;/title&gt; Tβ4 can promote scald wound healing in rats and may play a role via evoking Wnt/β-catenin pathway activation. &lt;/sec&gt;

유산균 복합배양 양배추 발효물의 항염증 효과

In this study, we investigated the anti-inflammation effect of cabbage (Brassica oleracea L var. capitata) fermented with a mixed culture of lactic acid bacteria (FCMC) and elucidated the underlying mechanism. The mixed culture included Lactobacillus plantarum and L. acidophilus. The cell viability of RAW264.7 macrophages were confirmed by MTT assay, and the results revealed no toxicity following treatment with FCMC at concentrations of up to 1,000 μg/mL. The anti-inflammatory effect of FCMC was evaluated by stimulating RAW264.7 macrophages with lipopolysaccharide (LPS) to induce the production of inflammation-related factors, which were measured by an nitric oxide (NO) assay, enzyme-linked immunosorbent, and Western blot. FCMC dose-dependently inhibited the production of NO, PGE2, and the pro-inflammatory cytokines IL-1β and TNF-α in LPS-stimulated RAW264.7 macrophages without any cytotoxicity. FCMC also reduced the protein expression levels of iNOS and COX-2 and inhibited the nuclear translocation of NF-κB and degradation of IκB in the LPS-stimulated cells. These results collectively suggest that FCMC may suppress the inflammatory reaction in LPS-stimulated RAW264.7 macrophages by regulating the NF-κB signaling pathway and function as an anti-inflammatory material.

Mechanism of Propofol-Lidocaine Hydrochloride Nano-Emulsion on Retinal Ganglion Cytopathic Effect in Diabetic Rats

The study drew attention to the influence mechanism of propofol and lidocaine hydrochloride nanoemulsion (NE) in the retinal ganglion cell pathology in diabetic rats. Specifically, the propofollidocaine hydrochloride NE was prepared using the emulsification method. The microscope and laser particle size analyser were used to observe the morphology and particle size of NE, respectively. Also, the viscosity of the NE and the recovery rate of the main ingredient were explored. 45 adult male Wistar rats were randomly divided into control group (PBS control), model group (diabetes model), and test group (diabetes model+propofol-lidocaine hydrochloride NE), with 15 rats in each group. The three groups were compared for the blood glucose, body weight, TNF-α and IL-1β mRNA levels in retinal tissue, and the number and apoptosis rate of ganglion cells. It was found that the average particle size of the NE was 89.76 nm, the maximum absorption wavelength was 280.0 nm, and the viscosity was 106.49 N/m/s. The average recovery rate of propofol in NE was 99.91%, and that of lidocaine hydrochloride was 99.80%. At 12th week after modeling, the blood glucose of the test group was lower versus the model group (P &lt; 0.05); the blood glucose and body weight of rats in the control group were lower than those in the other two groups (P &lt; 0.001). The test group exhibited lower mRNA levels of TNF-α and IL-1β and apoptosis index of retinal ganglion cells versus the model group (P &lt; 0.05). The model group showed a lower number of retinal ganglion cells versus the other two groups (P &lt; 0.05). It was inferred that propofol-lidocaine hydrochloride NE of a small particle size and good syringeability can notably reduce blood glucose, TNF-α and IL-1β mRNA levels, and retinal ganglion cell apoptosis index, and at the same time increase the number of retinal ganglion cells.

Evaluation the Role of IL-1βand TNFα with Asthma

Evaluation the Role of IL-1βand TNFα with Asthma

The effect of sinomenine eye drops on experimental dry eye in mice

Objective To investigate the effect of topical sinomenine (SIN) on ocular surface damage in experimental dry eye in mice. Material and methods Experimental dry eye was created using scopolamine hydrobromide in female C57BL/6 mice. Eye drops consisting of 0.05%, or 0.1% SIN or phosphate-buffered saline (PBS) were applied to the experimental dry eye in mice. Tear product and corneal staining scores were measured at 7 and 14 days after treatment. Interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels in the SIN groups at 14 days after treatment were compared with those of other groups. Results Mice treated with 0.05% or 0.1% SIN showed a significant improvement in tear product and corneal irregularity compared to the control and PBS-treated groups. A significant decrease in the levels of IL-1βand TNF-α was observed in the 0.05% and 0.01% SIN-treated groups. Conclusions Topical SIN eye drop application can effectively improve clinical signs and decrease inflammation in the ocular surface, and alleviate ocular surface damage in dry eye.

Effect of moxibustion on inflammatory factors and oxidative stress factors in patients with knee osteoarthritis: a randomized controlled trial

To compare the clinical efficacy between moxibustion and acupuncture for knee osteoarthritis (KOA), and to observe the effect on serum tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA). A total of 60 patients with KOA were randomized into a moxibustion group (30 cases, 2 cases dropped off) and an acupuncture group (30 cases, 2 cases dropped off). In the aucpuncture group, acupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Heding (EX-LE 2), Xuehai (SP 10), Liangqiu (ST 34), Zusanli (ST 36) and ashi point on the affected side for 30 min.In the moxibustion group, moxibustion was adopted at knee for 60 min. The treatment was given once every two days for 4 weeks, totally 14 times. Before and after treatment, the western ontario and McMaster universities osteoarthritis index (WOMAC) score was compared, and the therapeutic effect was evaluated in the two groups. The contents of serum TNF-αand IL-1β, the activity of serum SOD and the serum level of MDA were detected in the two groups. Compared before treatment, the WOMAC scores and the contents of serum TNF-α, IL-1β and MDA after treatment were reduced (P<0.05), the activity of serum SOD was increased (P<0.05) in the two groups. In the moxibustion group, the WOMAC score and the contents of serum TNF-α, IL-1β and MDA after treatment were lower than the acupuncture group (P<0.05), the activity of serum SOD was higher than the acupuncture group (P<0.05). The total effective rate was 89.3% (25/28) in the moxibustion group, which was superior to 42.9% (12/28) in the acupuncture group (P<0.05). Moxibustion and acupuncture can relieve KOA symptoms, and the therapeutic effect of moxibustion is superior to acupuncture. The mechanism may be related to the reduction of serum inflammatory factor and oxidative stress factor.

Berberine Inhibits the Gene Expression and Production of Proinflammatory Cytokines by Mononuclear Cells in Rheumatoid Arthritis and Healthy Individuals.

Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis. Berberine is an alkaloid isolated from Berberis vulgaris, and its anti-inflammatory effect has been identified. Twenty newly diagnosed RA patients and 20 healthy controls participated. Peripheral mononuclear cells were prepared and stimulated with bacterial lipopolysachharide (LPS,1 μg/ml), exposed to different concentrations of berberine (10 and 50μM) and dexamethasone (10-7 M) as a reference. The toxicity of compounds was evaluated by WST-1 assay. The expression of TNF-α and IL-1β was determined by quantitative real-time PCR. Protein level of secreted TNF-α and IL-1β was measured by using ELISA. Berberine did not have any toxic effect on cells, whereas Lipopolysaccharide (LPS) stimulation caused a noticeable rise in TNF-α and IL-1β production. Berberine markedly downregulated the expression of both TNF-α and IL-1β, and inhibited TNF-α and IL-1β secretion from LPS-stimulated PBMCs. This study provided a molecular basis for anti-inflammatory effect of berberine on human mononuclear cells through the suppression of TNF-a and IL-1secretion. Our findings highlighted the significant inhibitory effect of berberine on proinflammatory responses of mononuclear cells from rheumatoid arthritis individuals, which may be responsible for antiinflammatory property of Barberry. We observed that berberine at high concentration exhibited anti-inflammatory effect in PBMCs of both healthy and patient groups by suppression of TNF-a and IL-1cytokines at both mRNA and protein levels. Berberine may inhibit the gene expression and production of pro-inflammatory cytokines by mononuclear cells in rheumatoid arthritis and healthy individuals without affecting cell viability. Future studies with a larger sample size are needed to prove the idea.

Piperine protects LPS-induced mastitis by inhibiting inflammatory response

Mastitis, inflammation in the breast, affects breastfeedingwomenin the postpartumperiod. In the present study, we investigated the protective effects of piperine against mastitis using a mouse mastitis model. LPS-induced mastitis was established by injecting LPS into the canals of the mammary gland. Piperine was given intraperitoneally 1 h before and 12 h after LPS treatment. The results showed that the LPS-induced mammary histopathological changes and MPO activity were attenuated by piperine. LPS-induced inflammatory cytokines TNF-α andIL-1β were also inhibited by piperine. Furthermore, LPS-induced NF-κB activation was suppressed by the treatment with piperine. In addition, we found piperine dose-dependently increased the expression of PPARγ. All of these results suggested that piperine had protective effects against LPS-induced mastitis and that the mechanism may be mediated through the activation of PPARγ.

Formononetin Ameliorates Cognitive Disorder via PGC-1α Pathway in Neuroinflammation Conditions in High-Fat Diet-Induced Mice.

Alzheimer's disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer's disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-β generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer's disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer's disease with Formononetin. The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.

Comparison of intraperitoneal and intratesticular GYY4137 therapy for the treatment of testicular ischemia reperfusion injury in rats

Objective To investigate the efficacy of intraperitoneal GYY4137 therapy and intratesticular GYY4137 therapy to testicular ischemia reperfusion injury in an experimental rat model. Methods 4 groups were set up as the sham-operation group (group A), torsion/detorsion (T/D) group (group B), torsion/detorsion plus intraperitoneal GYY4137 (G-IP) group (group C), and torsion/detorsion plus intratesticular GYY4137 (G-IT) group (group D). Group A was the control group. In order to form a testicular T/D model, the left testis was operated and the rotation reached 720 degrees clockwise which lasted 1 hour before reperfusion in group B, group C and group D. Group C accepted 100 μmol/kg of GYY4137 intraperitoneally half an hour after testicular rotation, while group D was treated with the same dose by intratesticular injection. Four hours after detorsion, the testis was collected and subsequently assessed. The histopathological change of testis was observed with the help of hematoxylin and eosin (HE) staining; the expression of malondialdehyde (MDA) and superoxide dismutase (SOD) was measured; the apoptosis index was determined through TdT-mediated dUTP nick end labeling (TUNEL) methods; immunohistochemistry method was used to evaluate the expression of B cell lymphoma/leukemia-2 associated X protein (bax) and cysteinyl aspartate-specific protease (Caspase)-3; tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β expression was detected through Western blotting; real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to examine the expression of bax, Caspase-3, TNF-αand IL-1β. Results Group B showed significant changes in histology and an enhancement in the level of oxidative stress and apoptosis compared to the group A, which was relatively ameliorated in group C and group D. Compared with group A (1.21±0.20, 0.86±0.05), group B (5.13±0.26, 0.22±0.04) showed an increase in the MDA level and a decrease in SOD expression while the changes seemed to be eased in group C (3.26±0.23, 0.42±0.04) and group D (2.42±0.24, 0.58±0.04, t=37.790, 3.710, 17.040, 24.220, 11.450, 20.070, P<0.05). The expression of Caspase-3 and bax turned out to be strengthened by T/D in group B and relatively decreased with GYY4137 treatment in both group C and group D. Moreover, an enhancement of TNF-α and IL-1β expression was found in group B (0.774±0.042, 0.674±0.037) compared with group A (0.147±0.022, 0.136±0.018) while an inhabitation by GYY4137 in group C (0.425±0.029, 0.417±0.030) and group D (0.331±0.027, 0.308±0.025) was detected (t=21.620, 17.060, 28.060, 25.920, P<0.05). Compared with group B (5.35±0.43, 3.76±0.31, 4.35±0.31, 3.86±0.34), the expression of bax, Caspase-3, TNF-α and IL-1β was inhibited in group C (3.86±0.32, 2.56±0.21, 3.08±0.25, 2.92±0.28) and group D (3.78±0.36, 2.23±0.22, 2.96±0.26, 2.56±0.25). GYY4137, moderating these observed changes, displayed a more protective effect in group D compared to group C. The above results showed statistically significance (t=8.790, 10.130, 10.080, 6.750, 8.850, 12.730, 10.860, 9.740, P<0.05). Conclusion Our study indicated that GYY4137 treatment has obvious protective effect on testicular ischemia reperfusion injury in rats, and the efficacy of intratesticular therapy with GYY4137 is greater than that of intraperitoneal therapy, which may provide a more valuable approach for testicular torsion therapy. Key words: Testicular ischemia reperfusion; GYY4137; Apoptosis; Inflammation; Oxidative stress

Bmi1 Induces Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Under Inflammatory Environment

Bmi1 is a polycomb histone that regulates stem cells, but the role and mechanism of Bmi1 in bone marrow mesenchymal stem cells (BMSCs) differentiation has not been elucidated. Rat BMSCs were cultured in vitro and randomly divided into control group and inflammation group (treated with LPS). Bmi1 and Bmi1 siRNA were transfected into inflammatory BMSCs, followed by analysis of Bmi1 expression by Real time PCR, cell proliferation by MTT assay, Caspase3 activity, ALP activity, expression of Runx2, OP and PPARγ 2 by Real time PCR, as well as secretion of TNF-α and IL-1β by ELISA. In inflammatory environment, Bmi1 expression was significantly decreased, cell proliferation was significantly inhibited, along with increased Caspase3 activity, decreased ALP activity and the expression of Runx2 and OP, increased PPAR 2 expression and secretion of TNF-α and IL-1β (P &lt; 0 05). Transfection of Bmi1 siRNA into inflammatory BMSCs further significantly aggravated the above changes (P &lt; 0 05). Bmi1 plasmid transfected into inflammatory BMSCs significantly promoted Bmi1 expression and cell proliferation, decreased Caspase3 activity, increased ALP activity and expression of Runx2 and OP, decreased PPAR γ2 expression and TNF-α and IL-1β secretion (P &lt; 0 05). Bmi1 expression is reduced in BMSCs under inflammation. Up-regulation of Bmi1 can inhibit the secretion of inflammatory factors, regulate the proliferation and apoptosis of BMSCs, and promote the proliferation and osteogenic differentiation of BMSCs.

2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms.

2-Allylphenol (2-AP) is a synthetic phenylpropanoid, structurally related to cardanol, thymol, and ortho-eugenol. Phenylpropanoids are described in the literature as being capable of promoting biological activity. Due to the similarity between 2-AP and other bioactive phenylpropanoids, the present research aims at evaluating the antioxidant, antinociceptive, and anti-inflammatory potential of 2-AP in silico, in vitro, and in vivo. At 30 min prior to the start of in vivo pharmacological testing, administration of 2-AP (25, 50, 75, and 100 mg/kg i.p.), morphine (6 mg/kg i.p.), dexamethasone (2 mg/kg s.c.), or vehicle alone was performed. In the acetic acid-induced abdominal writhing tests, pretreatment with 2-AP significantly reduced the number of abdominal writhes, as well as decreased licking times in the glutamate and formalin tests. Investigation of the mechanism of action using the formalin model led to the conclusion that the opioid system does not participate in its activity. However, the adenosinergic system is involved. In the peritonitis tests, 2-AP inhibited leukocyte migration and reduced releases of proinflammatory mediators TNF-α and IL-1β. In vitro antioxidant assays demonstrated that 2-AP presents significant ability to sequester superoxide radicals. In silico docking studies confirmed interaction between 2-AP and the adenosine A2a receptor through hydrogen bonds with the critical asparagine 253 residues present in the active site. Investigation of 2-AP demonstrated its nociception inhibition and ability to reduce reactive oxygen species. Its interaction with A2a receptors may well be related to proinflammatory cytokines TNF-α and IL-1β reduction activity, corroborating its antinociceptive effect.

Protective effect of Yindan Pinggan Capsules on liver inflammatory injury and oxidative stress induced by acute alcoholic intake

To investigate the protective effect of Yindan Pinggan Capsules(YDPG)on acute alcoholic liver inflammatory injury and oxidative stress,sixty male Sprague-Dawley rats were divided into 6 groups randomly:normal group,model group,YDPG-L group,YD-PG-M group,YDPG-H group and Haiwang Jinzun(HWJZ)group.Except for the normal rats,while the remaining rats were administered orally with alcohol(50%,5 g·kg~(-1)).One hour after drinking,the rats in normal or model group were administered orally with PS,while the remaining rats were separately given YDPG(0.15,0.3,0.6 g·kg~(-1))or HWJZ(0.3 g·kg~(-1))for 10 days.After the last intragastric administration and fasting for 8 h,the HE staining was used to observe the pathological changes.The serum was used to determine the content of ALT,AST,ALP,TB,TP,LDH.The expressions of IL-1β,TNF-α,IL-10 and IL-4 in serum were detected by enzyme-linked immuno sorbent assay(ELISA).The content of SOD,MDA,GSH,GSP-Px in liver were determined.The results showed that both YDPGand HWJZ alleviated the liver injury induced by alcohol,decreased the activities of ALT,AST,ALP and LDH,down-regulated the expressions of TNF-αand IL-1β,up-regulated the expressions of IL-4 and IL-10;increased the activities of SOD,GSH,GSH-Px,but decreased the content of MDA.Therefore,the above results indicated that YDPG could protect the liver from alcoholic injury.