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1.
Neuromolecular Med ; 26(1): 15, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38653878

ABSTRACT

Lycium barbarum polysaccharide (LBP) have a certain curative effect on hypoglycemic and neuroprotective effects, but the specific mechanism is unclear and needs to be further explored. This study aimed to clarify the mechanisms of LBP in the treatment of ICV-STZ mice model of AD from the perspectives of insulin resistance, IRS1/PI3K/AKT signaling pathway, and synaptic protein expression. We used male C57BL/6J mice injected with STZ (3 mg/kg) in the lateral ventricle as an AD model. After treatment with LBP, the learning and memory abilities of ICV-STZ mice were enhanced, and the pathological changes in brain tissue were alleviated. LBP can regulate the expression of proteins related to the IRS1/PI3K/AKT signaling pathway and thereby reducing Aß deposition and tau protein phosphorylation in the brain of ICV-STZ mice. In addition, LBP also can up-regulate the expression of synaptic proteins. The results indicated that LBP played a neuroprotective role by regulating the IRS1/PI3K/AKT pathway, inhibiting tau protein hyperphosphorylation and improving the expression levels of synapse-related proteins.


Subject(s)
Alzheimer Disease , Drugs, Chinese Herbal , Insulin Receptor Substrate Proteins , Mice, Inbred C57BL , Neuronal Plasticity , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , tau Proteins , Animals , Male , Mice , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Brain/drug effects , Brain/metabolism , Brain/pathology , Cognition/drug effects , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Insulin Receptor Substrate Proteins/metabolism , Insulin Resistance , Neuronal Plasticity/drug effects , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Streptozocin , Synapses/drug effects , tau Proteins/metabolism
2.
Mol Neurobiol ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38311654

ABSTRACT

Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4 W) by utilizing a concentration of 0.5 mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side's forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI. This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries.

3.
J Neurol ; 270(2): 995-1003, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36329182

ABSTRACT

BACKGROUND AND PURPOSE: It has been proved that electrical vagus nerve stimulation can promote the recovery of motor function after stroke. There were no trials on the use of transcutaneous auricular electrical vagus nerve stimulation (ta-VNS) in patients with dysphagia after acute stroke. Our aim was to confirm whether ta-VNS can promote the recovery of swallowing function in these acute stroke patients with dysphagia. METHODS: We conducted a sham-controlled, double-blinded, parallel pilot study in 40 acute stroke patients randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training. The intensity of ta-VNS treatment was adjusted according to the patient's tolerance, 30 min each time, twice a day, five times a week, with a total course of 3 weeks. In the sham group, the parameters were the same except energy output. Swallowing function was assessed with Modified Mann assessment of swallowing ability (MASA), functional communication measure swallowing test (FCM), and the Rosenbek leakage/aspiration scale (RAS) according to swallowing video fluoroscopic (SVF) before the intervention (baseline, T0), immediately after the intervention (T1) and 4 weeks after the intervention (T2). RESULTS: After treatment, ta-VNS group statistically and clinically had larger change of MASA, FCM, and RAS scores compared with control group (P < 0.05) and this improvement continued at least 4 weeks after the end of treatment. There were no serious adverse events occurred during the whole intervention. CONCLUSION: The transcutaneous auricular electrical vagus nerve stimulation is effective as a novel and noninvasive treatment strategy for patients with dysphagia after acute stroke. TRIAL REGISTRATION: No: kelunshen No. 63 in 2020.


Subject(s)
Deglutition Disorders , Stroke , Vagus Nerve Stimulation , Humans , Vagus Nerve Stimulation/adverse effects , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Pilot Projects , Treatment Outcome , Stroke/complications , Stroke/therapy
4.
J Clin Pharm Ther ; 47(10): 1676-1683, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35765728

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: A previous randomized clinical trial concluded that an optimal concentration of 0.3% ropivacaine could provide satisfactory analgesia for breast cancer patients undergoing modified radical mastectomy. We wondered if a smaller volume (30 ml vs. 40 ml) of 0.3% ropivacaine could still provide adequate analgesia in an ultrasound-guided PECS II block in modified radical mastectomy. METHODS: We performed a prospective parallel randomized double-blind controlled clinical trial. Eligible patients were assigned to either the P30 or P40 group (30 or 40 ml of 0.3% ropivacaine, respectively). The skin area of hypoesthesia, anaesthetic plane determined with ultrasound, pain visual analogue scale (VAS), anaesthetic dosages, and complications were recorded. Serum levels of interleukin-1ß and interleukin-6 were measured postoperatively. RESULTS AND DISCUSSION: A total of 40 patients completed the trials, with 20 patients in each group. Although the skin area of hypoesthesia and the anaesthetic planes were significantly larger in the P40 group compared with the P30 group (p < 0.05), the VAS, analgesic and opioid doses, serum cytokine levels, anaesthetic toxicity, and complications had no significant differences between the two groups. WHAT IS NEW AND CONCLUSION: Compared with 40 ml, 30 ml of 0.3% ropivacaine could provide adequate analgesia and reduce surgical stress in patients undergoing modified radical mastectomy for breast cancer.


Subject(s)
Analgesia , Breast Neoplasms , Thoracic Nerves , Analgesics, Opioid , Breast Neoplasms/surgery , Double-Blind Method , Female , Humans , Hypesthesia/surgery , Interleukin-1beta , Interleukin-6 , Mastectomy , Mastectomy, Modified Radical/methods , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Prospective Studies , Ropivacaine , Ultrasonography, Interventional
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