Tumor Necrosis Factor-α Levels Research Articles

Qingzhuan dark tea polysaccharides-zinc alleviates dextran sodium sulfate-induced ulcerative colitis.

Qingzhuan dark tea polysaccharides (QDTP) have been complexed with Zinc (Zn) to form the Qingzhuan dark tea polysaccharides-Zinc (QDTP-Zn) complex. The present study investigated the protective effects of QDTP-Zn on ulcerative colitis (UC) in mice. The UC mouse model was induced using dextran sodium sulfate (DSS), followed by oral administration of QDTP-Zn (0.2 and 0.4 g kg-1 day-1). QDTP-Zn demonstrated alleviation of UC symptoms in mice, as evidenced by a decrease in disease activity index scores. QDTP-Zn also regulated colon tissue injury by upregulating ZO-1 and occludin protein expression, at the same time as downregulating tumor necrosis factor-α and interleukin-6β levels. Furthermore, QDTP-Zn induced significant alterations in the abundance of bacteroidetes and firmicutes and notably increased levels of short-chain fatty acids (SCFAs), particularly acetic acid, propionic acid, and butyric acid. In summary, QDTP-Zn exhibits therapeutic potential in alleviating enteritis by fortifying the colonic mucosal barrier, mitigating inflammation and modulating intestinal microbiota and SCFAs levels. Thus, QDTP-Zn holds promise as a functional food for both the prevention and treatment of UC. © 2024 Society of Chemical Industry.

Protective Effect of Shenfu Injection against Sepsis-induced Acute Lung Injury by Suppressing Inflammation and Apoptosis Through the Regulation of the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Pathway

Abstract Objective: Sepsis-induced acute lung injury (ALI) is a clinically critical condition with a high mortality rate. Shenfu injection (SFI) is a Chinese herbal medicine extracted from red ginseng and Aconite, Radix Aconiti, with various pharmacological activities. This study aimed to investigate the potential mechanism of action of SFI in preventing sepsis-induced ALI. Materials and Methods: We established a mouse model of sepsis-induced ALI by cecal ligation and puncture (CLP). The mice were randomly divided into three groups (n = 8): Sham, CLP, and SFI (10 mL/kg). Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for pathological analysis, enzyme-linked immunosorbent assay, immunohistochemistry (IHC), and protein detection. Results: Our results showed that SFI significantly ameliorated pathological damage caused by CLP-induced ALI. SFI treatment significantly decreased the lung wet-to-dry weight ratio. In addition, SFI treatment significantly reduced the protein levels and cell numbers in the BALF. SFI could significantly reduce the levels of tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1β in plasma and BALF. SFI significantly reduced the protein expression of Bax and cleaved caspase-3 and increased the protein levels of Bcl-2. Western blotting and IHC results showed that SFI reduced the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Conclusions: In a septic ALI mouse model, SFI inhibited apoptosis and inflammation through the JAK2/STAT3 pathway, providing a candidate drug for the treatment of septic ALI.

Cynaroside ameliorates methotrexate-induced enteritis in rats through inhibiting NLRP3 inflammasome activation

IntroductionCynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms.MethodsTo assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation.ResultsAdministration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats.DiscussionCollectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.

The role of the immune system in depersonalisation disorder

Objectives Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. Methods We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. Results We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. Conclusions The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD.

The Histological and Biochemical Assessment of Monoiodoacetate-Induced Knee Osteoarthritis in a Rat Model Treated with Salicylic Acid-Iron Oxide Nanoparticles.

Iron oxide nanoparticles (IONPs) represent an important advance in the field of medicine with application in both diagnostic and drug delivery domains, offering a therapeutic approach that effectively overcomes physical and biological barriers. The current study aimed to assess whether oral administration of salicylic acid-functionalized iron oxide nanoparticles (SaIONPs) may exhibit beneficial effects in alleviating histological lesions in a murine monoiodoacetate (MIA) induced knee osteoarthritis model. In order to conduct our study, 15 Wistar male rats were randomly distributed into 3 work groups: Sham (S), MIA, and NP. At the end of the experiments, all animals were sacrificed for blood, knee, and liver sampling. Our results have shown that SaIONPs reached the targeted sites and also had a chondroprotective effect represented by less severe histological lesions regarding cellularity, altered structure morphology, and proteoglycan depletion across different layers of the knee joint cartilage tissue. Moreover, SaIONPs induced a decrease in malondialdehyde (MDA) and circulating Tumor Necrosis Factor-α (TNF-α) levels. The findings of this study suggest the therapeutic potential of SaIONPs knee osteoarthritis treatment; further studies are needed to establish a correlation between the administrated dose of SaIONPs and the improvement of the morphological and biochemical parameters.

An exploratory metabolomic study reveals the Dipsacus asper-Achyranthes bidentate herb pair against osteoarthritis by modulating imbalance in polyunsaturated fatty acids and energy metabolism

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the cartilage. The therapeutic potential of the Dipsacus asper-Achyranthes bidentate herb pair for OA has been acknowledged, yet its precise mechanism remains elusive. In this study, we conducted a comprehensive analysis of metabolomic changes and therapeutic outcomes in osteoarthritic rats, employing a gas chromatography-mass spectrometry-based metabolomics approach in conjunction with histopathological and biochemical assessments. The rats were divided into six groups: control, model, positive control, Dipsacus asper treated, Achyranthes bidentata treated, and herb pair treated groups. Compared to the model group, significant reductions in levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and iNOS were observed in the treated groups. Multivariate statistical analyses were employed to investigate metabolite profile changes in serum samples and identify potential biomarkers, revealing 45 differential biomarkers, with eighteen validated using standard substances. These analytes exhibited excellent linearity across a wide concentration range (R2>0.9990), with intra- and inter-day precision RSD values below 4.69% and 4.83%, respectively. Recoveries of the eighteen analytes ranged from 93.97% to 106.59%, with RSD values under 5.72%, underscoring the method's reliability. Treatment with the herbal pair effectively restored levels of unsaturated fatty acids such as linoleic acid and arachidonic acid, along with glucogenic amino acids. Additionally, levels of phosphoric acid and citric acid were reversed, indicating restoration of energy metabolism. Collectively, these findings highlight the utility of metabolomic analysis in evaluating therapeutic efficacy and elucidating the underlying molecular mechanisms of herb pairs in OA treatment.

Logic-Based Strategy for Spatiotemporal Release of Dual Extracellular Vesicles in Osteoarthritis Treatment.

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1β levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.

Impact of intraoperative dexmedetomidine on postoperative delirium and pro-inflammatory cytokine levels in elderly patients undergoing thoracolumbar compression fracture surgery: A prospective, randomized, placebo-controlled clinical trial.

This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients undergoing thoracolumbar compression fracture surgery. In this randomized, double-blind, placebo-controlled trial conducted from October 2022 to January 2023 at Anting Hospital in Shanghai, 218 elderly patients were randomized into DEX (n = 110) and normal saline (NS, n = 108) groups. The DEX group received 0.5 µg/kg/h DEX, and delirium incidence was assessed using the Confusion Assessment Method (CAM) on days 1 to 3 post-surgery. Levels of interleukins IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured pre-operation (T0) and on postoperative days 1 (T1) and 3 (T3). Preoperative (T0) and postoperative day 1 (T1) cerebrospinal fluid (CSF) samples were treated with varying concentrations of olanzapine or DEX to observe their regulatory effects on the expression of Phospho-ERK1/2 and Phospho-JNK. Dexmedetomidine significantly lowered the incidence of POD to 18.2%, compared to 30.6% in the NS group (P = .033). While all patients showed an initial increase in cytokine levels after surgery, by T3, IL-6 and TNF-α levels notably decreased in the DEX group, with no significant change in IL-1β levels across groups. The adverse events rate was similar between groups, demonstrating the safety of DEX in this population. In postoperative CSF samples, treatment with 0.5 mM DEX significantly downregulated Phospho-JNK and upregulated Phospho-ERK1/2 expression, demonstrating a dose-dependent modulation of inflammatory responses. Dexmedetomidine is effective in reducing early POD in elderly patients post-thoracolumbar compression fracture surgery. It also decreases IL-6 and TNF-α levels, indicating its potential in managing postoperative inflammatory responses. Treatment with 0.5 mM DEX significantly modulated Phospho-ERK1/2 and Phospho-JNK expressions in postoperative CSF samples, indicating a dose-dependent effect on reducing inflammation. This study contributes to understanding DEX's role in improving postoperative outcomes in elderly patients.

Mechanism of Bacillus coagulans T242 in prevention of Salmonella infection in mice

Salmonella is recognized as an important foodborne pathogen, which seriously threatens human safety. Bacillus coagulans T242 (T242) could prevent the growth of Salmonella and alleviate Salmonella infection in Caco-2 cells in vitro. The main objective of this study was to investigate the mechanism of action of T242 in preventing Salmonella infection in mice. Both T242 vegetative cells and spore prevention groups could reduce the bacterial loads in the ileum, liver and spleen of Salmonella typhimurium (S. typhi) SL1344 infected mice, and reduce the levels of Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in serum and also increase the expression of Interleukin-1β (IL-1β) in serum, Monocyte chemoattractant protein-1 (MCP-1) and Inducible nitric oxide synthase (iNOS) in the liver, Interleukin-22 (IL-22) and Interleukin-23 (IL-23) in the ileum, and tight junction proteins (Claudin-1, Occludin and ZO-1) in the colon, and regulate intestinal flora. Pretreatment of T242 spores could downregulate the relative abundance of Desulfovibrionaceae in Salmonella infected mice. The relative abundance of Ruminococcus in Salmonella-infected mice was down-regulated by T242 vegetative cells preconditioning. The results showed that T242 prevented the systemic spread of Salmonella by regulating intestinal flora and enhancing intestinal barrier function against Salmonella invasion, inducing anti-inflammatory effects and regulating immune responses. T242 had great potential in controlling the epidemic of foodborne pathogens and was expected to be an effective alternative to antibiotic therapy, which is of great significance for the control and defense of Salmonella infection.

Granulocyte- Macrophage Colony-Stimulating Factor Reverses Immunosuppression Acutely Following a Traumatic Brain Injury and Hemorrhage Polytrauma in a Juvenile Male Rat Model.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.

Effects of three-duration Tai-Chi exercises on depression and sleep quality in older women.

This study aims to explore the effects of 24weeks of three-duration Tai-Chi (TC) practice on depression and sleep quality in older women. A total of 124 older women were randomly divided into four groups: short-time group (SG, n = 31, mean age: 65.3), medium-time group (MG, n = 30, mean age: 65.7), long-time group (LG, n = 32, mean age: 64.9) and control group (CG, n = 31, mean age: 66.2). The Beck Depression Inventory (BDI) and Pittsburgh Sleep Quality Index (PSQI), and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and 5-hydroxytryptamine (5-HT) were measured. 1) Within-group comparisons: Compared with the baseline, the 12th and 24th weeks showed reductions in TNF-α and IL-6 levels and increase in 5-HT level in the SG, MG and LG (p < 0.05). The LG at the 24th week had reduced BDI and PSQI scores (p < 0.05). Compared with the 12th week, the 24th week showed reductions in TNF-α and IL-6 levels (p < 0.01) and increase in 5-HT level (p < 0.05) in the SG, MG, and LG. 2) Between-group comparisons: The SG, MG, and LG had lower TNF-α and IL-6 levels and higher 5-HT level than the CG at 12th and 24th weeks (p < 0.05). At the 24th week, the LG had lower BDI and PSQI scores than the CG and lower TNF-α level than the SG and MG (p < 0.05). The MG had lower TNF-α levels than the SG in the 24th week (p < 0.01). These results indicate that older individuals may undertake at least 12weeks of TC exercise with a duration of 60min per session to significantly improve depressive mood and sleep quality.

Effect of hydroxyapatite coating thickness on inflammation and osseointegration of Ti–29Nb–13Ta-4.6Zr (TNTZ) implants

The study investigates the effect of Hydroxyapatite (HA) coating thickness on the inflammation and osseointegration properties of Ti–29Nb–13Ta-4.6Zr (TNTZ) implants for orthopedic implant applications. TNTZ screws were used as based samples, and the HA coating was deposited using an Electrophoretic Deposition (EPD) method to achieve various coating thickness. The thin (50–70 μm), medium (70–90 μm), and thick (90–110 μm) coating thicknesses were obtained by applying different voltage and time exposure during the EPD process, while the uncoated screw was used as the control sample. The screws were implanted into the right tibia of male Rattus norvegicus Wistar rats, and the animals were kept in cages and provide with ad libitum food for two weeks. After termination of the test animals, blood samples were collected to measure levels of Tumor Necrosis Factor-α (TNF-α) using an ELISA method, and a removal torque test was performed on the implanted screws. Additionally, tibial bone tissue around the implant area was collected for histopathology analysis. The result of the study indicate that HA coating thickness has an effect on TNF-α concentration, removal torque value, and new bone growth. The optimal thickness of the HA layer was found to be in the medium range (70–90 μm), resulting in low inflammation levels, relatively high osseointegration rates, and optimal new bone tissue growth. These finding are expected to be applicable in future orthopedic implant applications.

Comparative efficacy of sweated and non-sweated Salvia miltiorrhiza Bge. extracts on acute myocardial ischemia via regulating the PPARα/RXRα/NF-κB signaling pathway

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

Tectorigenin inhibits inflammatory responses in murineinflammatory bowel disease and LPS-stimulated macrophages via inactivating MAPK signaling pathway.

Considering the antihepatitis effects of Tectorigenin (TEC), and the same adenosine mitogen-activated protein kinase (MAPK) pathway in both hepatitis and inflammatory bowel disease (IBD) models, exploring the role of TEC in IBD is contributive to develop a new treatment strategy against IBD. The IBD mouse model was constructed by feeding with dextran sodium sulfate (DSS) and injection of TEC. Afterward, the mouse body weight, colon length, and disease activity index (DAI) were tested to assess the enteritis level. Mouse intestine lesions were detected by hematoxylin and eosin staining. Murine macrophages underwent lipopolysaccharide (LPS) induction to establish an inflammation model. Cell viability was determined by cell counting kit-8 assay. Enzyme-linked immunosorbent assay was performed to measure interleukin 6(IL-6) and tumor necrosis factor-α (TNF-α) levels. Cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS) expressions were quantified via quantitative reverse transcription polymerase chain reaction. Levels of MAPK pathway-related proteins (p-P38, P38, p-Jun N-terminal kinase(JNK), JNK, signal-regulated kinase(ERK), p-ERK), COX-2 and iNOS were quantitated by Western blot. TEC improved the inflammatory response through ameliorating weight loss, shortening colon, and increasing DAI score in IBD mouse. Expressions of intestinal inflammatory factors (IL-6, TNF-α, iNOS and COX-2) and MAPK pathway-related proteins (p-P38, p-JNK, and p-ERK) were increased both in DSS-induced mouse intestinal tissue, but TEC inhibited expressions of inflammatory factors. The same increased trend was identified in LPS-induced macrophages, but TEC improved macrophage inflammation, as evidenced by downregulation of inflammatory factors. TEC mitigates IBD and LPS-induced macrophage inflammation in mice via inhibiting MAPK signaling pathway.

A Formulation of Combined Poria cocos and Cordyceps militaris Rice Ameliorates Depressive-like Effects by Downregulating p38 MAPK Signaling Pathways

Background and aimPoria cocos (PC) is traditional Chinese medicine with sedative, diuretic, and tonic properties. Cordyceps militaris rice (CMR) is a matrix used for the solid-state culture of C. militaris, which has been used for anti-angiogenetic and anti-inflammation effects. To investigate a formulation of combined Poria cocos and Cordyceps militaris rice (PC-CMR) alleviates anxiety behaviours and depressive-like effects for the first time. Experimental procedureAfter five-week of stress, rats were induced by unpredictable chronic mild stress (UCMS) treated with PC-CMR formulation. Then, rats underwent various behavior tests, testing serum inflammatory mediators by enzyme-linked immunosorbent assays (ELISA), evaluated monoamines by high-performance liquid chromatography (HPLC) analysis, and protein expression by western blotting. ResultsTreatment with doses of formulated PC-CMR reversed sucrose preference and increased amount of time spent on the open arms in rat behavioral tests. The formulated PC-CMR significantly reduced glutamate content and turnover rates of serotonin and dopamine in the prefrontal cortex of rats. In the inflammation-related pathway, PC-CMR decreased interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in serum and downregulated the expression of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the prefrontal cortex and signal transducer and activator of transcription 3 (STAT3), and indoleamine 2,3-dioxygenase (IDO) in the amygdala. ConclusionOur findings suggest that the formulated PC-CMR could have antidepressive and anxiolytic effects by modulating neurotransmitter levels and reducing inflammation.

Antimicrobial and anti-inflammatory effects of BenTooth: A natural product blend of burdock root, persimmon leaf extracts, and quercetin on periodontal disease

Periodontal disease represents a condition that exhibits substantial global morbidity, and is characterized by the infection and inflammation of the periodontal tissue effectuated by bacterial pathogens. The present study aimed at evaluating the therapeutic efficacy of BenTooth, an edible natural product mixture comprising burdock root extract, persimmon leaf extract and quercetin, against periodontitis both in vitro and in vivo. BenTooth was examined for antimicrobial properties and its impact on cellular responses related to inflammation and bone resorption. Its effects were also assessed in a rat model of ligature-induced periodontitis. BenTooth demonstrated potent antimicrobial activity against P. gingivalis and S. mutans. In RAW264.7 cells, it notably diminished the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as reduced interleukin-6 and tumor necrosis factor-α levels triggered by P. gingivalis-derived lipopolysaccharide. Furthermore, BenTooth inhibited osteoclastogenesis mediated by the receptor activator of nuclear factor κB ligand. In the rat model, BenTooth consumption mitigated the ligature-induced expansion in distance between the cementoenamel junction and the alveolar bone crest and bolstered the bone volume fraction. These results present BenTooth as a potential therapeutic candidate for the prevention and remediation of periodontal diseases.

Unlocking renal Restoration: Mesaconine from Aconitum plants restore mitochondrial function to halt cell apoptosis in acute kidney injury

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor β1 (TGF-β1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1β (interleukin-1β) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.

The cGAS/STING signaling pathway is involved in sevoflurane induced neuronal necroptosis via regulating microglia M1 polarization

ObjectiveThe specific mechanisms of sevoflurane-induced neurotoxicity are still undetermined. The aim of the current study was to investigate the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in sevoflurane-induced neuronal necroptosis. MethodsBV2 microglial cells were divided into a control group and a 4% sevoflurane exposure group. Western blotting was used to detect expression of the M1 polarization marker inducible nitric oxide synthase (iNOS). RNA was collected for RNA sequencing analysis. After STING knockdown in microglia, western blotting was performed to examine expression of the pro-inflammatory markers CD16 and CD32. The tumor necrosis factor-α (TNF-α) level in media was detected using an enzyme-linked immunosorbent assay. BV2 microglia conditioned media was collected to incubate HT22 neuronal cells, and their cell activity was measured using a CCK8 assay. Calcium was observed by fluorescence. Western blotting was performed to evaluate receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) expression. Neuronal necroptosis rate were detected using flow cytometry. ResultsSevoflurane exposure promoted microglial M1 polarization. The cGAS/STING pathway was screened and identified by RNA sequencing analysis of sevoflurane-exposed microglia and the control group. Compared with the control group, STING knockdown in microglia rescued the amoeboid morphology, inhibited TNF-α release, and significantly decreased iNOS, CD16, and CD32 expression. Moreover, calcium ions and necroptosis within neurons were decreased, and RIPK1, RIPK3, and p-MLKL expression was markedly decreased in microglia media culture with STING knockdown. ConclusionThese results suggest that sevoflurane can regulate microglial M1 polarization by activating the cGAS/STING signaling pathway and increasing immune factor release, thus accelerating the neuronal necroptosis induced by calcium overload.

Chemical constituents from Notopterygium incisum and their anti-neuroinflammatory activity

Phytochemical research on an extract of Notopterygium incisum yielded fifteen compounds (1–15), including four previously undescribed compounds (10−13). The structures of the unreported compounds were elucidated by spectroscopic and spectrometric data analysis such as 1D and 2D NMR, IR and HR-ESI-MS. Compounds 1–5 and 10–14 were isolated from N. incisum for the first time. 7S⁎,8R⁎-Phenethyl-(7-methoxy-8-isoeugenol)-ferulate (10), 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) are the undescribed ferulic acid derivatives. Additionly, the anti-neuroinflammatory effects of compounds were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. The pharmacological results showed that 6β,10β-epoxy-4α-hydroxy-guaiane (6), teuclatriol (7) and 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) inhibited the production and expression of nitric oxide (NO) in the LPS-induced BV2 cells in a concentration-dependent manner. Acorusnol (4), teucladiol (9), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) only inhibited the release of NO at concentration of 20 μM. Moreover, 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) reduced the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated BV2 cells. The results demonstrated 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) could be a potential anti-neuroinflammatory agent and is worthy of further study.

The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway

ObjectiveThe present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochondrial dynamic via PI3K-AKT pathway.MethodsThirty-two female rats were randomly divided into four experimental groups: Sham, PCOS, PCOS + MSCs, and PCOS + MSCs + LY294002. The Sham group received 0.5% w/v carboxymethyl cellulose (CMC); the PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. Animals in the PCOS + MSCs group received 1 × 106 MSCs/rat (i.p,) on the 22th day of the study. In the PCOS + MSCs + LY294002 group, rats received LY294002 (PI3K-AKT inhibitor) 40 min before MSC transplantation. Mitochondrial dynamic gene expression, mitochondrial membrane potential (MMP), citrate synthase (CS) activity, oxidative stress, inflammation, ovarian histological parameters, serum hormone levels, homeostatic model assessment for insulin resistance (HOMA-IR), insulin and glucose concentrations, p-PI3K and p-AKT protein levels were evaluated at the end of the experiment.ResultsPCOS rats showed a significant disruption of mitochondrial dynamics and histological changes, lower MMP, CS, ovary super oxide dismutase (SOD) and estrogen level. They also had a notable rise in insulin and glucose concentrations, HOMA-IR, testosterone level, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, ovarian malondialdehyde (MDA) content as well as a notable decrease in p-PI3K and p-AKT protein levels compared to the Sham group. In the PCOS + MSCs group, the transplantation of MSCs could improve the above parameters. Administration of LY294002 (PI3K-AKT pathway inhibitor) deteriorated mitochondrial dynamic markers, oxidative stress status, inflammation markers, hormonal levels, glucose, and insulin levels and follicular development compared to the PCOS + MSCs group.ConclusionsThis study demonstrated that the protective effects of MSC transplantation in regulating mitochondrial dynamics, promoting mitochondrial biogenesis, competing with redox status and inflammation response were mainly mediated through the PI3K-AKT pathway in the PCOS model.