Protective effect of Huanglianjiedu Decoction on microcystin-LR induced nerve injury.

Microcystin-LR (MC-LR) presented in eutrophic water has been identified as having the capacity to induce damage to the mammalian nervous system by crossing the blood-brain barrier through organic anion transporting polypeptides. However, the lack of effective preventive and protective strategies remains a concern. Huanglianjiedu Decoction (HLJD), a classical Chinese traditional formula originating from the Tang Dynasty and comprising Rhizoma Coptidis, Radix Scutellariae, Cortex Phellodendri, and Fructus Gardeniae, has exhibited neuroprotective effects attributed to its antioxidant properties. In this study, we investigated the potential of HLJD in counteracting the neurotoxic effects induced by MC-LR. Our findings revealed that MC-LR dose-dependently inhibited the activity of the PP2A enzyme in PC 12 cells and significantly elevated the phosphorylation levels of JNK, ERK1/2, and p38. Moreover, MC-LR administration resulted in synaptic damage in mouse neurons, hyperphosphorylation of the microtubule-related protein Tau, cognitive impairment, and deficits in learning and memory in C57BL/6J mice. Notably, HLJD effectively reversed the cytotoxicity caused by MC-LR in PC 12 cells, and attenuated MC-LR-induced neuronal damage while improving learning ability in mice. These results highlight the potential of HLJD as a promising protective strategy against MC-LR-induced neurological injury.

Acupuncture and moxibustion therapy for cognitive impairment: the microbiome-gut-brain axis and its role.

Cognitive impairment poses a significant burden on individuals, families, and society worldwide. Despite the lack of effective treatment strategies, emerging evidence suggests that the microbiome-gut-brain (MGB) axis may play a critical role in the pathogenesis of cognitive impairment. While targeted treatment is not yet comprehensive, recently, acupuncture and moxibustion therapy has participated increasingly in the treatment of degenerative diseases and has achieved a certain therapeutic effect. In this review, the possible mechanisms by which acupuncture and moxibustion therapy may improve cognitive impairment through the MGB axis are reviewed, including regulating gut microbial homeostasis, improving intestinal inflammation mediated by the neuroendocrine-immune system, and enhancing intestinal barrier function. We also discuss common acupoints and corresponding mechanism analysis to provide insights into further exploration of mechanisms that target the MGB axis and thereby intervene in cognitive impairment.

Phosphodiesterase 4B is required for NLRP3 inflammasome activation by positive feedback with Nrf2 in the early phase of LPS- induced acute lung injury.

Acute lung injury (ALI) is associated with overproduction of inflammatory mediators in lung tissue. Previous studies have revealed that inflammation induces activation of phosphodiesterase 4B (PDE4B) accompanied by the production of inflammatory mediators, but the detailed mechanism remains unclear. Here, we focused on the NOD-, LRR- and pyrin domain-containing protein 3(NLRP3) inflammasome complexes to study the crosstalk between PDE4B and NF-E2-related factor 2 (Nrf2). We used global knockout PDE4B or Nrf2 mice to prepare LPS induced acute lung injury model by intratracheally administration, and LPS primed bone marrow-derived macrophages (BMDMs), following overexpression of PDE4B or Nrf2, luciferase activity analysis, and chIP-qPCR analyses. We found that deficiency of PDE4B could potently attenuate the lung histopathological changes, suppress the secretion of pro-inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, IL-18, and cleaved caspase-1, 8, and GSDMD accompanied with defective activation of the ROS/Nrf2/NLRP3. Meanwhile deficiency of Nrf2 showed the similar results. Furtherly, overexpression by PDE4B or Nrf2 plasmid transfection in MH-S cells could enhance the Nrf2 or PDE4B expression. Luciferase analysis suggested that Nrf2 activated PDE4B promoter activity, while PDE4B could increase Nrf2 substrate ARE activity in MH-S cells in dose dependent manners. ChIP-qPCR analyses showed that Nrf2 bound to the PDE4B promoter region at Ì´ 1532 to Ì´1199 position in macrophages. Altogether, deficiency of PDE4B inhibit the inflammasome activation and pyroptosis in LPS stimulated lung injury model and macrophages by regulating ROS/Nrf2/NLRP3 activation. The study provides new insight that PDE4B is required for NLRP3 inflammasome activation by positive feedback with Nrf2.

Cardioprotective effect of electroacupuncture in cardiopulmonary bypass through apelin/APJ signaling.

Aim Acupuncture, particularly electroacupuncture (EA), can improve the clinical outcomes of cardiopulmonary bypass (CPB) patients; however, the mechanisms remain unclear. This study aimed to examine the effects of EA pre-treatment on myocardial injury after CPB and investigate its potential mechanisms. MAIN METHODS: Male Sprague-Dawley rats were subjected to CPB and divided into Control (sham-operated), CPB, and EA (CPB + EA) groups. In the EA group, rats were treated with EA at the "PC6" acupoint for 30 min before being subjected to CPB. At 0.5, 1, and 2 h after CPB, the expression levels of plasma cardiac troponin I (cTnI) and lactate dehydrogenase (LDH), and myeloperoxidase (MPO) activity, TNFα, IL-1ß, reduced glutathione (GSH), oxidized glutathione (GSSH), and the ratio of GSH/GSSH in the myocardial tissue were measured. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining. The expression of cleaved caspase-3 was detected by immunofluorescence. The expression of apelin, APJ, AKT, p-Akt, ERK1/2, and p-ERK1/2 was determined using western blotting. KEY FINDINGS: Decreased myocardial injury marker levels, myocardial apoptosis, oxidative stress, and the inflammatory response were found in the EA group compared with the CPB group. The expression levels of apelin, APJ, and p-Akt/AKT were increased in the EA group, and the p-ERK1/2/ERK1/2 level was decreased. SIGNIFICANCE: This study showed that EA pre-treatment can protect the heart from damage following CPB, which might be mainly mediated by restoring the apelin/APJ signaling pathway.

Electroacupuncture ameliorates cardiopulmonary bypass induced apoptosis in lung via ROS/Nrf2/NLRP3 inflammasome pathway.

AIMS: Electroacupuncture (EAc) has a pulmonary protective effect during cardiopulmonary bypass (CPB), but its molecular mechanisms including inflammasome activation signaling pathways remains unclear. MATERIALS AND METHODS: Male Sprague Dawley rats were divided into control, CPB + EAc and CPB groups. Lung injury model was developed by CPB treatment and EAc (2/100 Hz) was carried out before CPB in the CPB + EAc group. Lung tissues were collected at two time points (0.5 h; 2 h) to determine cytokines release by ELISA kits, and protein expressions by Western blot. Serum collected at two time points (0.5 h; 2 h) from CPB and CPB + EAc treated groups were used in NR8383 cells to confirm the effect of EAc. KEY FINDINGS: CPB significantly increased the inflammatory mediators, histological damage and expression of inflammasome related protein and apoptosis, when compared with control group. The level of tumor necrosis factor-α(TNF-α), interleukin (IL)-18 and IL-1ß in the CPB + EAc treated group was significantly decreased along with histological changes compared to CPB. Moreover, EAc inhibited the activation of Nod like receptor protein-3 (NLRP3) inflammasome complex, caspase-8 and activated NF-E2-related factor 2 (p-Nrf2). In addition, serum from the CPB + EAc group prevented CPB induced activation of inflammasome and related mediators, reducing ROS generation and apoptosis in NR8383 macrophages. SIGNIFICANCE: These findings indicate that EAc had a critical anti-apoptotic role by suppression of ROS/Nrf2/NLRP3 inflammasome pathway. EAc might be a possible therapeutic treatment for CPB-induced acute lung injury.

Protective Effects of Acupuncture in Cardiopulmonary Bypass-Induced Lung Injury in Rats.

Acute lung injury caused by cardiopulmonary bypass (CPB) increases the mortality after cardiac surgery. Our previous clinical study suggested that electroacupuncture (EAc) has a protective effect during CPB, but the mechanism was unclear. So, we design this study to investigate the effects of EAc on CPB-induced lung injury and the underlying mechanism. Male Sprague Dawley rats were randomly divided into control, CPB, and CPB + EAc groups. A lung injury model was created by CPB surgery to serve as the CPB group, and EAc (2/100 Hz) was used before CPB in the CPB + EAc group. Lung tissue was collected at 0.5, 1, and 2 h after CPB. Pulmonary malondialdehyde (MDA) concentrations as well as superoxide dismutase (SOD), myeloperoxidase (MPO), and caspase-3 activity were determined. c-Jun N-terminal kinase (JNK), ERK, p38 and cleaved caspase 3 in the lung were analyzed by western blotting. A549 cells were treated by rat serum from the CPB and CPB + EAc groups, and cleaved caspase-3 activity was detected by fluorescent immunohistochemistry. CPB significantly increased the MPO activity, MDA content, apoptosis, caspase-3 activity, and phosphorylated p38 but decreased SOD activity compared with the control group. EAc significantly increased SOD activity at 0.5 and 2 h (p < 0.01 vs CPB) and reduced CPB-induced histological changes, MPO activity at 1 and 2 h (p < 0.05 vs CPB), MDA content at 2 h (p < 0.05 vs CPB), caspase-3 activity at 1 h (p < 0.05 vs CPB), and phosphorylated p38 and JNK at 0.5 h after CPB. The serum from the CPB group increased more positive staining cells of cleaved caspase-3 than that from the CPB + EAc group. EAc reversed the CPB-induced lung inflammation, oxidative damage, and apoptosis; the mechanism may involve decreased phosphorylation of p38 along with caspase-3 activity and activation.

Electroacupuncture with different current intensities to treat knee osteoarthritis: a single-blinded controlled study.

BACKGROUND: To assess the efficacy of Electroacupuncture (EA) stimulation with high-intensity compared with low-intensity on knee osteoarthritis (KOA). METHODS: Participants with KOA were randomized to either high-intensity EA group or low-intensity EA group. EA was applied unilaterally on the affected leg with the local points GB34, ST34, EX-LE4, EX-LE5, ST36, and SP9. The visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured before and after participation. Plasma TNFα, IL-1ß, IL-6, and apelin levels were also assessed by enzyme immunoassay (ELA) before and after treatment. RESULTS: Of 80 participants who consented to study participation, 77 completed the program. The patients showed a significant improvement in their pain, stiffness, and physical function on the VAS and WOMAC, accompanying with a significantly reduction in plasma levels of apelin and TNFα. Furthermore, high-intensity group exhibited statistically significant improvements in stiffness and physical function symptoms compared with low-intensity group. Plasma level of IL-6 was significantly decreased only after high-intensity EA treatment. Furthermore, apelin level was significantly inhibited in high-intensity EA group than in low-intensity EA group. CONCLUSIONS: Both high- and low-intensity EA treatments alleviate the clinical symptoms of KOA patients. High-intensity EA is more effective than low-intensity EA. Changes in plasma levels of TNFα, apelin and IL-6 may be involved in the therapeutic effect of EA on KOA.

[Clinical experience of Qin's eight scalp needles for treatment of Parkinson's disease].

The eight scalp needles, founded by Professor QIN Liang-fu, and its clinical experience for treatment of Parkinson's disease (PD) are introduced. Based on his years of clinical experience, it is proposed by Professor QIN that the Governor Vessel is mainly for miscellaneous disease and disease of limbs. Combined with distribution of cephalic motor region and meridian, an acupuncture treatment plan that is full of innovativeness is proposed, which is called Qin's eight scalp needles. It includes bilateral Fengchi (GB 20), Shuaigu (GB 8), Toulinqi (GB 15) as well as Yintang (GV 29) and Baihui (GV 20), mainly for treatment of nervous system diseases, such as PD and multiple sclerosis and so on. Besides, some outpatient cases are introduced to explain that eight scalp needle could alleviate the progression of PD, improve patients' motor, cognitive and affective disorders, reduce the suffering of patients, and improve the patient's quality of life.

Combination of transcranial direct current stimulation and methylphenidate in subacute stroke.

Noninvasive transcranial direct current stimulation (tDCS) and methylphenidate (MP) are associated with motor recovery after stroke. Based on the potentially complementary mechanisms of these interventions, we examined whether there is an interactive effect between MP and tDCS. In this preliminary study, we randomized subacute stroke subjects to receive tDCS alone, MP alone or combination of tDCS and MP. A blinded rater measured safety, hand function, and cortical excitability before and after treatment. None of the treatments caused any major or severe adverse effects or induced significant differences in cortical excitability. Analysis of variance of gain score, as measured by Purdue pegboard test, showed a significant between-group difference (F(2,6)=12.167, p=0.008). Post hoc analysis showed that the combination treatment effected greater Purdue pegboard gain scores than tDCS alone (p=0.017) or MP alone (p=0.01). Our preliminary data with nine subjects shows an interesting dissociation between motor function improvement and lack of motor corticospinal plasticity changes as indexed by transcranial magnetic stimulation in subacute stroke subjects.

Molecular mechanisms underlying the effects of acupuncture on neuropathic pain.

Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity following chronic constriction injury, es-pecially electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function.

Dissociation of motor task-induced cortical excitability and pain perception changes in healthy volunteers.

BACKGROUND: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. CONCLUSIONS/SIGNIFICANCE: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training.