Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome. / ç”µé’ˆå¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ è¡Œä¸ºå­¦åŠæµ·é©¬ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.

Rutaecarpine ameliorates imiquimod-induced psoriasis-like dermatitis in mice associated with alterations in the gut microbiota.

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice. The model mice are treated with 1% rutaecarpine (RUT) (external use) or the oral administration of RUT at different concentrations. Furthermore, high-throughput 16S rRNA gene sequencing is applied to analyze the changes in the diversity and composition of the gut microbiota. Based on the observation of mouse dorsal skin changes, RUT can protect against inflammation to improve psoriasis-like skin damage in mice. Additionally, RUT could suppress the expression levels of proinflammatory cytokines (IL-23, IL-17A, IL-22, IL-6, and IFN-α) within skin tissue samples. Concerning gut microbiota, we find obvious variations within the composition of gut microflora between IMQ-induced psoriasis mice and RUT-treated psoriasis mice. RUT effectively mediates the recovery of gut microbiota in mice induced by IMQ application. Psoriasis is linked to the production of several inflammatory cytokines and gut microbiome alterations. This research shows that RUT might restore gut microbiota homeostasis, reduce inflammatory cytokine production, and ameliorate psoriasis symptoms. In conclusion, the gut microbiota might be a therapeutic target or biomarker for psoriasis that aids in clinical diagnosis and therapy.

Ursolic acid alleviates cancer cachexia by inhibiting STAT3 signaling pathways in C2C12 myotube and CT26 tumor-bearing mouse model.

Cancer cachexia, a multi-organ disorder resulting from tumor and immune system interactions, prominently features muscle wasting and affects the survival of patients with cancer. Ursolic acid (UA) is known for its antioxidant, anti-inflammatory, and anticancer properties. However, its impact on cancer cachexia remains unexplored. This study aimed to assess the efficacy of UA in addressing muscle atrophy and organ dysfunction in cancer cachexia and reveal the mechanisms involved. UA dose-dependently ameliorated C2C12 myotube atrophy. Mechanistically, it inhibited the expression of muscle-specific RING finger containing protein 1 (MURF1) and the phosphorylation of signal transducer and activator of transcription 3 (STAT3), and upregulated the mRNA or protein levels of myogenic differentiation antigen and myogenin in cultured C2C12 myotubes treated with conditioned medium. In vivo, UA protected CT26 tumor-bearing mice against loss of body weight, as well as increased skeletal muscle and epididymal fat without affecting tumor growth. Additionally, UA increased food intake in CT26 tumor-bearing mice. The mRNA expression of tumor necrosis-α and interleukin 6 was significantly downregulated in the intestine, gastrocnemius, and heart tissues following 38 d UA administration. UA treatment reversed the levels of myocardial function indicators, including creatine kinase, creatine kinase-MB, lactate dehydrogenase, car-dial troponin T, and glutathione. Finally, UA treatment significantly inhibited the expression of MURF1, the phosphorylation of nuclear factor kappa-B p65, and STAT3 in the gastrocnemius muscle and heart tissues of cachexic mice. Our findings suggest that UA is a promising natural compound for developing dietary supplements for cancer cachexia therapy owing to its anti-catabolic effects.

Clinical and Animal Studies of Waist and Knee Scraping Therapy for Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a degenerative condition with knee pain as the main clinical manifestation. Scraping is one of the commonly used traditional Chinese medicine treatment methods, which activates blood circulation, removes blood stasis, reduces inflammation, and so on. Although scholars have proposed that the synergistic treatment of the waist and knee for KOA is superior to simple knee treatment, there is no relevant reference literature on the application of scraping therapy. Therefore, this study aims to explore the effectiveness and potential mechanisms of waist and knee scraping therapy for treating KOA through clinical and animal studies in order to promote its clinical application. OBJECTIVE: To explore the clinical efficacy of waist and knee scraping therapy in the treatment of KOA from clinical study and increase animal study on this basis to preliminarily explore its mechanism, providing an objective basis for better treatment of KOA. METHODS: The clinical study recruited 90 KOA patients and divided them into a control group, a knee scraping group, and a waist and knee scraping group using a random number table method. All patients were evaluated for clinical efficacy, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Score. The KOA rat model was established using the Hulth method. The rats were randomly divided into a control group, KOA group, waist scraping group, knee scraping group, and waist and knee scraping group. During the intervention process of rats, the pain sensitivity threshold was measured, and HE staining was performed on the synovium and cartilage. The protein and mRNA expression levels of TNF-α, IL- 1ß, IL-6, PGP9.5, SP and TRPA1, TRPV4, SP, and NGF were measured by Western blot and real-time PCR. RESULTS: In the clinical study, the clinical efficacy of the 2 scraping groups was significantly higher than that of the control group. The clinical efficacy of the waist and knee scraping group on the 60th day of treatment was significantly higher than that of the knee scraping group. In terms of improving WOMAC scores, all 3 groups had significance; The function and total score of the waist and knee scraping group on the 28th day of treatment, as well as the pain, function, and total score on the 60th day, were lower than those of the knee scraping group. In terms of improving pain while standing, pain when walking on flat ground, and total score, the scraping group had significant differences. The score of heavy limbs in the waist and knee scraping group was lower than that in the knee scraping group. In an animal study, during the 4th week after modeling, there were differences in the pain sensitivity threshold between the KOA group and the waist scraping group compared to the control group, while there were differences in the pain sensitivity threshold between the knee scraping group and the waist and knee scraping group compared to the KOA group. The expression levels of various proteins and genes in the KOA group and waist scraping group increased compared to the control group; The knee scraping group and the waist and knee scraping group were lower than those in the KOA group. CONCLUSION: Scraping therapy can significantly alleviate knee joint pain and stiffness, improve joint function, and improve clinical efficacy, and the short-term and long-term effects of waist and knee scraping therapy are more significant. The scraping therapy has a definite therapeutic effect on KOA rats, which can improve the threshold of cold hyperalgesia and mechanical hyperalgesia, and the waist and knee scraping therapy is more obvious. This may be related to reducing inflammatory reactions in synovial and ganglion tissues.

Study on the mechanism of puerarin against osteoarthritis from ferroptosis based on network pharmacology and bioinformatics.

Network pharmacology and bioinformatics were used to study puerarin's molecular mechanism in treating osteoarthritis from the perspective of ferroptosis, revealing a new treatment target. Ferroptosis-related targets were obtained from FerrDb. Puerarin action targets were retrieved from TCMSP, Pharmmappe, SwissTargetPrediction, and Targetnet databases, and supplemented with PubMed. The gene expression profiles of GSE12021, GSE55235, and GSE82107 were obtained using "Osteoarthritis" as the search term in the GEO database, and the differential expression gene screening analysis was performed for osteoarthritis. The intersection targets between puerarin, iron death, and osteoarthritis were obtained using Venn diagrams. GO and KEGG analyses were conducted with R software. Molecular docking and visualization of puerarin and core targets were performed using Autodock Vina and PyMol software. The effects of puerarin on the cell viability and the TNFα, IL6, and Ilß levels of human inflammation articular chondrocytes were tested in vitro experiments. Puerarin, ferroptosis, and osteoarthritis share four targets: PLIN2, PTGS2, VEGFA, and IL6. GO enrichment analysis showed that puerarin maintained the blood-brain barrier, regulated peptide serine phosphorylation, and had anti-inflammatory effects. KEGG analysis showed that puerarin's anti-inflammatory effects were mainly through VEGF, IL-17, C-type lectin receptor, HIF-1, TNF, and other signaling pathways. Puerarin closely bound PLIN2, PTGS2, VEGFA, and IL6 targets in molecular docking. In vitro, puerarin prevented osteoarthritis. Network pharmacology and bioinformatics explained puerarin's multi-target and multi-pathway treatment of OA, which may be related to ferroptosis, and confirmed its anti-inflammatory effect.

Effect of acupuncture on arthritic pathological injury in rats with type â ¡ collagen-induced rheumatoid arthritis. / é’ˆåˆºæ”¹å–„â ¡åž‹èƒ¶åŽŸè›‹ç™½è¯±å¯¼æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ååº”çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of acupuncture stimulation of "Yanglingquan"(GB34), "Zusanli"(ST36) and "Xuanzhong" (GB39) on arthritis index (AI), joint synovial membrane pathology, serum-related immunoinflammatory factors, and expressions of tumor suppressor gene mt-p53, nuclear factor kappa B (NF-κB) and peroxisome proliferator activated receptor gamma (PPARγ) in knee joint synovial tissue of rats with type Ⅱ collagen-induced arthritis (CIA), so as to explore its possible mechanisms underlying improvement of rheumatoid arthritis (RA). METHODS: Male SD rats were used in the present study. The CIA model was established by subcutaneous injection of collagen emulsion (200 µL/rat) in the tail root region on the first day and repeat (100 µL/rat) once on the 9th day. Eighteen successful CIA rats were randomized into model, medication and acupuncture groups, with 6 rats in each group. Other 6 normal rats were used as the normal control group. For rats of the medication group, leflunomide (1.9 mg/kg) was administrated by gavage, once a day, and for rats of the acupuncture group, manual acupuncture stimulation was applied to bilateral GB34, ST36, GB39 for 30 min, once a day, for 12 weeks. The arthritis index (AI) score (0-4 points) was evaluated once every week. The contents of IL-6, IL-17 and TNF-α in the serum were determined by ELISA. Histopathological changes of the ankle joint were observed by H.E. staining. The protein and mRNA expression levels of mt-p53, NF-κB p65, and PPARγ in the knee joint synovial tissue were determined by Western blot and quantitative real time PCR, separately. RESULTS: Compared with the normal control group, the AI scores at different time-points after modeling, contents of serum TNF-α, IL-6 and IL-17, expression levels of mt-p53, NF-κB p65, PPARγ proteins and mRNAs were significantly increased in the model group (P<0.01, P<0.05). In comparison with the model group, the AI scores at the 10th week in the medication group and at the 3rd, 9th and 10th week in the acupuncture group, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of mt-p53 and NF-κB p65 proteins in both medication and acupuncture groups, as well as mt-p53 and NF-κB p65 mRNAs in the medication group were apparently decreased (P<0.01, P<0.05), while the expression levels of PPARγ protein in both medication and acupuncture group and PPARγ mRNA in the medication group were significantly up-regulated (P<0.05, P<0.01). No significant differences were found between the acupuncture and medication groups in down-regulating the AI score and serum TNF-α, IL-6 and IL-17 contents. The effect of acupuncture was weaker than that of medication in down-regulating the expression of mt-p53 and NF-κB p65 proteins and mRNAs and in up-regulating PPARγ mRNA (P<0.01). H.E. results showed ankle cartilage hyperplasia, reduced joint cavity, mild fibroproliferation and inflammatory cell infiltration in the surrounding soft tissue of the ankle joint in rats of the model group, which was milder in both medication and acupuncture groups. CONCLUSIONS: Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.

Citropten alleviates acute and recurrent colitis via blockage of NF-κB and JAK/STAT3 pathways.

Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD.

Multi-effective characteristics and advantages of acupuncture in COVID-19 treatment.

Coronavirus disease 2019 (COVID-19) is a major disease that threatens human life and health. Its pathogenesis is complex and still not fully clarified. The clinical treatment is mainly supportive and lacks specific treatment methods. Acupuncture treatment can inhibit immune inflammatory reactions, neuroinflammatory reactions, oxidative stress levels, and hypothalamus-pituitary-adrenal (HPA) axis activity, improve lung function, and relieve migraine, fatigue, anxiety, and depression. However, whether acupuncture treatment is suitable for treating these symptoms in patients with COVID-19 still needs to be investigated. For this review, the literature was systematically searched for multiple databases to summarize the mechanisms of acupuncture treatment for COVID-19-related symptoms and complications. A complex network analysis of acupoints and symptoms was also performed to clarify acupoint selection in the acupuncture treatment of symptoms related to COVID-19. The evidence indicates that acupuncture can improve the respiratory, digestive, nervous, and mental and psychological symptoms related to COVID-19 by inhibiting immune inflammatory reactions, regulating intestinal flora, mitochondrial function, oxidative stress level, cardiomyocyte apoptosis, neurotransmitter release, and HPA axis activity, and alleviating basic diseases such as diseases of the vascular system. Acupuncture can improve various clinical and concomitant symptoms of COVID-19; however, its mechanism of action is complex and requires further study. Graphical abstract: http://links.lww.com/AHM/A54.

Antipyretic and Anti-Inflammatory Effects of Rectal Administration of Reduning Injection in Feverish Rats Induced by Lipopolysaccharide.

This study aimed to explore the antipyretic and anti-inflammatory effects of rectal administration of Reduning injection in feverish rats induced by lipopolysaccharide (LPS), and observe the temperature changes and inflammatory indexes. The selected rats were randomly divided into 6 groups, with 10 rats in each group, named as normal empty group, model group, intravenous group (2 mL/kg), low-dose enema group (1 mL/kg), middle-dose enema group (2 mL/kg), and high-dose enema group (4 mL/kg). The hourly temperature variations in rats injected with LPS in the abdomen were recorded. Five hours later, blood samples from the abdominal aorta were collected to monitor immunoglobulin M (IgM), immunoglobulin A (IgA), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. At 5 hours, the fever peak induced by LPS appeared, and obvious antipyretic effects were observed; the effect was optimal in the medium dose enema group at 4 hours (p < 0.05); the IgM value in the enema groups, the intravenous group, and normal empty group was significantly lower than that in the model group; the IgA value in each group was higher than that in the model group, but there was no statistical significance (p > 0.05); values of IL-6 and TNF-α in each group were lower than those in the model group, and the difference was statistically significant except for the high-dose enema group (p > 0.05). Low-dose and medium-dose rectal administration of Reduning injection have inhibitory effects on IL-6, TNF-α, and IgM in feverish rats induced by LPS, but there is no obvious difference compared to intravenous administration and it could achieve an anti-inflammatory effect. There is a possibility of enhancing IgA immunity with rectal administration, but there is no obvious difference compared to intravenous administration, and rectal administration has no significant effect on mucosal immunity.

Effects of repetitive transcranial magnetic stimulation combined with acupuncture on NLRP3 inflammasome and protease levels in patients with neuropathic pain.

PURPOSE: This study aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS) combined with acupuncture could alleviate pain in patients suffering from postherpetic neuralgia (PHN) by inhibiting NOD-like receptor 3 (NLRP3) inflammasome activation. METHODS: Data of 92 PHN patients were retrospectively collected. The patients were grouped as control (nerve block), rTMS, and rTMS + acupuncture groups according to treatment methods. The visual analogue scale (VAS) score, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, NLRP3, and Caspase-1 levels of patients in each group prior and post-treatment were analyzed. RESULTS: The rTMS + acupuncture group showed higher efficacy than the rTMS group and the control group, contributing to markedly lower VAS score, as well as TNF-α, IL-1ß, IL-6, NLRP3 and Caspase-1 levels than the other two groups (P < 0.05). CONCLUSION: rTMS plus acupuncture can reduce the inflammatory immune response and ease the pain in patients by inhibiting NLRP3 inflammasome and its resulting inflammatory factors, Caspase-1 and IL-1ß.

The Effects and Potential Mechanisms of Moxibustion for Rheumatoid Arthritis-Related Pain: A Randomized, Controlled Trial.

Purpose: To investigate the effects of moxibustion in relieving pain, and other clinical symptoms for patients with rheumatoid arthritis (RA), and explore the potential mechanism of moxibustion treatment for RA. Patients and Methods: Seventy qualified RA patients were randomly assigned in a 1:1 ratio to the moxibustion group or the routine group. The routine group only took oral methotrexate tablets and folic acid tablets. The moxibustion group was treated with moxibustion based on oral pharmaceutical. Moxibustion was performed two times weekly for 8 weeks, a total of 16 sessions. Patients scored their pain on a visual analog scale (VAS). The American College of Rheumatology improvement criteria of 20%, 50% and 70% (ACR20, ACR50 and ACR70) after treatment were investigated. Clinical symptoms, a disease activity score using 28 joint counts (DAS28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), health assessment questionnaire (HAQ), interleukin 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) of RA patients were analyzed before and after treatment. Results: After treatment, the VAS scores, tender and swollen joint counts, morning stiffness scores, disease activity scores (DAS28, SDAI, CDAI), HAQ scores in the two groups were both improved, and the effects of moxibustion group were more obvious (P < 0.05). The ACR20 and ACR50 of the moxibustion group were greater than that of the routine group (P < 0.05), no significant difference of the ACR70 existed between the two groups (P > 0.05). In addition, the decreases of IL-1ß, TNF-α, VEGF of the moxibustion group were better than that of the routine group (P < 0.05). Conclusion: Moxibustion could effectively relieve pain, ameliorate the clinical symptoms, and decrease the disease activity of RA. The potential mechanism may be the decrease in the level of serum inflammatory factors.

[Mechanisms of moxibustion preconditioning underlying improving learning-memory ability by regulating polarization of microglia via TLR4/NF-κB signaling pathway in AD rats].

OBJECTIVE: To observe the effect of moxibustion preconditioning on learning-memory ability, Toll like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signal pathway related proteins and microglia in rats with Alzheimer's disease (AD), so as to explore its possible mechanisms underlying improvement of AD. METHODS: Male SD rats were randomly divided into normal, sham operation, AD model and pre-moxibustion groups, with 9 rats in each group. Moxibustion was applied to "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) for 15 min, once daily, 6 days as a course of treatment for 3 courses. At the end of moxibustion, the AD model was established by injection of Aß25-35 aggregation solution into the bilateral hippocampus. The sham operation group was only injected with the same amount of 0.9% Nacl solution. The spatial learning-memory ability of rats was detected by Morris water maze test, the ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM). The histopathological changes of hippocampus tissue were observed by HE staining, and the protein expression levels of TLR4 and NF-κB p65 in the hippocampus detected by Western blot, and the positive expressions of Iba-1, CD80 and CD206 in the hippocampal CA1 region were detected by immunofluorescence labeling. The contents of inflammatory factors IL-1ß, TNF-α and IL-10 in the hippocampus were measured by ELISA. RESULTS: Compared with the sham operation group, the escape latency was significantly increased (P<0.01), and the number of platform quadrant crossing times was decreased (P<0.01) in the model group. In comparison with the model group, the increased escape latency and the decreased platform quadrant crossing times were reversed in the pre-moxibustion group (P<0.01). TEM and light microscope observation showed loose arrangement of cells, enlarged cell space, degeneration, swelling and deformation of hippocampal neurons, rupture of membranes of a large number of cells, reduction of mitochondria, dilation of endoplasmic reticulum, and matrix vacuoles, uneven distribution of organelles and cytoplasm, and being difficult in distinguishing the nuclear cytoplasm in the model group, which was relatively milder in the pre-moxibustion group. The expression levels of hippocampal NF-κB p65 and TLR4, the mean immunofluorescence density of Iba-1 and CD80, as well as the contents of IL-1ß and TNF-α in hippocampal CA1 region were significantly increased in the model group than those in the sham operation group (P<0.01), and obviously decreased in the pre-moxibustion group than those in the model group (P<0.05, P<0.01). Whereas the expression of CD206 and the content of IL-10 were evidently decreased in the model group than those in the sham operation group (P<0.01), and strikingly increased in the pre-moxibustion group than those in the model group (P<0.01). No significant differences were found between the sham operation group and the normal group in all the indexes mention above (P>0.05). CONCLUSION: Pre-moxibustion at GV20, BL23 and ST36 can improve learning-memory ability in AD rats, which may be associated with its functions in promoting the polarization of microglia from M1 to M2 and reducing the neuroinflammatory response by way of TLR4/NF-κB signaling pathway.

[Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke].

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION: Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.

Correlation between MRI features and CSF inflammatory factor levels in patients with infarction or TIA, assessed by contrast-enhanced high-resolution MRI.

OBJECTIVE: To explore the correlation between the time course of CE-T1WI plaque and the level of CSF inflammatory factors in patients with cerebral infarction or TIA assessed by contrast-enhanced high-resolution MRI. METHODS: From August 2019 to December 2021, 136 patients with ischemic stroke-related neurological symptoms or suspected ischemic stroke in Gong'an County Hospital of Traditional Chinese Medicine were retrospectively analyzed, including 69 men and 67 women aged 45-80 years old, with an average age of 65.98±8.29. The study was divided into two groups: infarction group (patients with high DWI signal in the middle cerebral artery supply area, n=68) and TIA group (patients with ischemic neurologic symptoms but no relevant imaging findings, n=68). Patients with grade 1 or grade 2 image quality were included in the study after imaging with a 3.0T MRI device. Unenhanced MRI (T1WI and T2WI) and contrast-enhanced T1WI (CE+T1WI) plaque signals were compared between the two groups. The expression levels of TNF-α, IL-6, and IL-1ß in CSF of the two groups were detected by ELISA. VAMLN, LAMLN, PA, stenosis rate, and reconstruction index were compared between the two groups. The SNR and CNR values on T1WI and CE+T1WI were compared. The expression levels of TNF-α, IL-6, and IL-1ß detected by ELISA in cerebrospinal fluid of patients with CE-T1WI plaque enhancement were compared. RESULTS: The expression levels of TNF-α, IL-6, and IL-1ß in the cerebral infarction group were higher than those in the TIA group (P<0.05). Comparing the VAMLN, LAMLN, PA, stenosis rate and remodeling index of the two groups, the VAMLN, PA, and remodeling index of the cerebral infarction group were higher than in the TIA group (P>0.05), and there was no significant difference in VAMLN and stenosis rate between groups (P<0.05). Comparing the plaque SNR and CNR values on T1WI and CE+T1WI, the signal intensity, adjacent signal intensity, SNR, and CNR of carotid plaque on CE+T1WI were higher than those on T1WI (P>0.05). The expression levels of TNF-α, IL-6, and IL-1ß in the moderate enhancement group were higher than those in the non-enhancement group, and the expression levels of TNF-α, IL-6 and IL-1ß in the high enhancement group were higher than those in the moderate enhancement group (P<0.05). CONCLUSION: The temporal variation of CE-T1WI plaque was positively correlated with the level of cerebrospinal fluid inflammatory factors. High levels of inflammatory factors, positive remodeling, and significant enhancement were closely related to unstable plaque, which may increase the risk of stroke in patients with atherosclerosis.

Effect of Electroacupuncture on the Treatment of Pneumonia in Patients with Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: Pneumonia is a serious postoperative complication of hypertensive intracerebral hemorrhage (HICH), and there is no specific treatment for pneumonia. In this study, we conducted randomized controlled trials to evaluate the effects of electroacupuncture (EA) on the treatment of pneumonia in patients with HICH. METHODS: An equal number of patients with HICH complicated with pneumonia (n = 80 in total) were randomly placed in either the EA group (EA treatment and routine basic treatment) or the control group (routine basic treatment). After 14 days of treatment, clinical symptoms and signs, blood oxygen saturation, the level of inflammatory factors, the effective rate, the scores of the Barthel Index, National Institutes of Health Stroke Scale and Glasgow Coma Scale, the hospitalization time, and expenses were compared between the groups. RESULTS: The general information of the patients in the control and EA groups were similar. After 14 days of intervention, the patients in the EA group showed better symptom and sign scores, blood oxygen saturation levels, Barthel Index scores, Glasgow Coma Scale scores, and National Institutes of Health Stroke Scale scores than the patients in the control group. Furthermore, the EA treatment also lowered the levels of inflammatory factors and white blood cell count. Additionally, the patients in the EA group showed higher effective rates than those in the control group. CONCLUSIONS: EA benefits the treatment of pneumonia in patients with HICH.

Sodium New Houttuyfonate Effectively Improves Phagocytosis and Inhibits the Excessive Release of Inflammatory Factors by Repressing TLR4/NF-Кb Pathway in Macrophages.

BACKGROUND: Sodium new houttuyfonate (SNH) is an adduct of houttuyfonate, which is the main component of the common Chinese medicinal plant Houttuynia cordata. SNH has been widely used in antibacterial and anti-inflammatory treatments in clinics. However, the exact antimicrobial mechanism of SNH is still unclear, despite its mild direct antimicrobial activity in vitro. Objectives: The aim of this study is to investigate the effect and possible mechanism of SNH on macrophages against bacteria in vitro. METHODS: In this study, we assessed the antibacterial and anti-inflammatory effects of SNH on the RAW264.7 macrophage cell line against Pseudomonas aeruginosa, a major opportunistic pathogen. RESULTS: Firstly, we found that SNH showed minimal toxicity on RAW264.7 macrophages. Secondly, our results indicated that SNH effectively inhibited the inflammatory reaction of macrophages stimulated by P. aeruginosa. We also found that SNH improved the phagocytosis and killing effect of RAW264.7 macrophages against P. aeruginosa in vitro. Furthermore, our results revealed that SNH effectively inhibited the expression of the TLR4/NF-кB pathway in macrophage RAW264.7 co-incubated with P. aeruginosa in vitro. CONCLUSION: Based on our findings, SNH can significantly improve the phagocytosis of macrophages and inhibit the excessive release of inflammatory factors by repressing the TLR4/NF-кB pathway.

[Effects of different acupuncture and moxibustion methods on articular cartilage morphology and NF-κB p65/NLRP3 pathway in rats with knee osteoarthritis].

OBJECTIVE: To compare the effects of filiform needling, electroacupuncture (EA) and moxibustion on articular cartilage morphology and nuclear transcription factor-κB (NF-κB) p65/ Nod-like receptor protein 3 (NLRP3) pathway in rats with knee osteoarthritis (KOA). METHODS: Wistar rats were randomly divided into blank control， model, filiform needling, EA and moxibustion groups, with 8 rats in each group. The KOA model was established by injecting sodium iodoacetate into the right knee cavity. Filiform needling, EA and moxibustion groups were treated with the right side of "Dubi" (ST35) and "Neixiyan" (EX-LE5), and were given filiform needling, EA and mild moxibustion therapies for 15 min respectively, once every other day, for a total of 4 weeks. The diameter of the right knee joint was observed. The ultrastructure of knee chondrocytes was observed by transmission electron microscope. The contents of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-18 were determined by ELISA. The expression levels of NF-κB p65, NLRP3, apoptosis-related speckle like protein (ASC) and TNF-α in knee cartilage were dectected by Western blot. RESULTS: Compared with the blank control group, the right knee joint cavity was narrowed, chondrocytes were constricted significantly, mitochondria were moderately swollen, the diameter of the right knee was increased, and the contents of serum TNF-α, IL-1ß and IL-18 were increased (P<0.01), the expressions of NF-κB p65, NLRP3 and TNF-α in knee cartilage were increased (P<0.01) while the expression of ASC was decreased (P<0.01) in the model group.Compared with model group, the narrowed knee joint cavity and chondrocyte injury were improved， knee diameter decreased (P<0.01, P<0.05), and the content of serum TNF-α and the expression of NLRP3 in knee cartilage were decreased (P<0.05, P<0.01) in 3 treatment groups; the contents of serum IL-1ß and IL-18, and the expression of TNF-α in knee cartilage were decreased (P<0.01, P<0.05), while the expression of ASC in knee cartilage was increased (P<0.01) in EA and moxibustion groups; the expression of NF-κB p65 in knee cartilage was decreased (P<0.01) in moxibustion group. Compared with EA group, the content of serum IL-18 was decreased (P<0.05) in moxibustion group. CONCLUSION: Filiform needling, EA and moxibustion can all reduce the formation of knee osteophytosis in KOA rats, alleviate joint cavity narrowing, improve the ultrastructure of articular cartilage, reduce the level of inflammatory factors, regulate the NF-κB p65/NLRP3 pathway. Moxibustion has the most obvious regulatory effect among the 3 treatment methods.

Anti-Inflammatory Activity of Panax notoginseng Flower Saponins Quantified Using LC/MS/MS.

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However, Panax notoginseng flower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX-2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL-37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography-tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX-2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.

The Effect and Mechanism of Sancao Lichang Decoction on Diarrhea- Predominant Irritable Bowel Syndrome by Regulating Tlr4/Myd88/Nf-Κb Pathway.

OBJECTIVE: To evaluate the effect of Sancao Lichang decoction as traditional Chinese medicine on diarrhea-predominant irritable bowel syndrome (IBS-D) and TLR4/MyD88/NF-κB pathway. BACKGROUND: Traditional Chinese medicine has made significant progress in preventing and treating irritable bowel syndrome, and its efficacy has been validated by clinical practice. Sancao Lichang decoction is an empirical prescription developed by professor Tang Decai that has been used for many years to treat chronic diarrhoea with good curative effec. Still, its mechanism of action on IBS-D is unknown. METHODS: The study sample of Fifty SD rats was randomly divided into a blank group, model group, low-dose group, medium-dose group, and high-dose group (n = 10). The IBS-D rat models were established by restraining stress method and acetic acid enema. After different treatments, defecation frequency, fecal water content (FWC), serum IL-6 and TNF-α contents, and protein level of TLR4/MyD88/NF-κB in colon tissues were detected separately. RESULTS: The indexes of rats in each group were significantly different. The increase in body weight in the medium-dose and high-dose groups was significantly higher than that in the model group (p < 0.05). Compared with the model group, the medium and high dose groups had lower diarrhea frequency, FWC, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) (p < 0.05). The expression levels of TLR4, MyD88, and NF-κB protein in the colon of the three groups treated with Sancao-Lichan decoction were significantly lower than those in the model group (p < 0.01). After different treatments, the colonic mucosa of rats in each group was stained with HE, which proved that the structural damage of colonic mucosa was improved after treatment with Sancao Lichang decoction, and the improvement effect was dose-dependent. CONCLUSION: Sancao Lichang decoction may reduce IBS-D by inhibiting TLR4/MyD88/NF-κB pathway, inhibiting the inflammatory response, and improving intestinal mucosal barrier function.

[Early electroacupuncture intervention delays progression of disease in mice with amyotrophic lateral sclerosis by down-regulating TLR4/NF-κB signaling].

OBJECTIVE: To observe the effect of early electroacupuncture (EA) intervention on Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in mice with amyotrophic lateral sclerosis (ALS), so as to explore its mechanisms underlying alleviation of ALS. METHODS: Fifty-four ALS (ALS-SOD1G93A) mice with SOD1G93A gene mutation identified by PCR were randomly divided into model group, 60 day(d) EA group and 90 d EA group(n=18 mice in each group), and other 18 ALS-SOD1G93A negative mice were used as the control group. At the age of 60 and 90 days, mice of the two EA groups received EA (2 Hz, 1 mA) stimulation of bilateral "Jiaji" (EX-B2) of L1-L2 and L5-L6 for 20 min, twice a week for 4 weeks,respectively. When being 60 days old, the mice in the model and control groups were subjected to the same binding as that in the two EA groups but without EA intervention. The tail suspension test was used to judge the onset time of disease and the survival period, and rotary rod fatigue test was used to evaluate the hind limb motor function. Nissl staining method was used to observe the content of Nissl bodies in the anterior horn of the lumbar spinal cord. Immunohistochemical staining was used to observe the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in the anterior horn of the lumbar spinal cord, and Western blot was used to detect the relative expression of TLR4, NF-κB and tumor necrosis factor-α (TNF-α) in the lumbar spinal cord. RESULTS: The disease onset time apparently delayed in the 60 d EA group than in the model group (P<0.01). The survival time was apparently shorter in the model group than in the control group (P<0.01), and obviously prolonged in the 60 d EA and 90 d EA groups than in the model group (P<0.01). The rotatory rod time was obviously shorter in the model group than in the control group (P<0.05), and apparently longer in the 60 d EA group than in the model group and 90 d EA group (P<0.05). Compared with the control group, the model group had a decrease in the number of Nissl bodies in the anterior horn of the lumbar spinal cord (P<0.01), and an increase in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.01). In contrast to the model group, both 60 d EA and 90 d EA groups had an apparent increase in the number of Nissl bodies and a marked decrease in the expression levels of Iba-1, TLR4, NF-κB and TNF-α in the lumbar spinal cord (P<0.05, P<0.01). The therapeutic effects of 60 d EA group were evidently superior to those of 90 d EA group in delaying the onset time of disease, prolonging the survival time and rotatory rod time, increasing the number of Nissl bodies, and in down-regulating the expression of Iba-1, TLR4, NF-κB and TNF-α (P<0.05, P<0.01). CONCLUSION: The early intervention of EX-B2 EA is more effective in delaying the progression of ALS than post-onset intervention in ALS-SOD1G93A mice, which may be related to its functions in inhibiting the excessive activation of microglia, and down-regulating TLR4/NF-κB signaling.