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Dystonia is supposed to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted the established cerebellar dystonia mice model by injecting ouabain to examine the contribution of the cerebellum. Initially, we examined whether the entopeduncular nucleus (EPN), substantia nigra pars reticulata (SNr), globus pallidus externus (GPe), and striatal neurons were activated in the model. Next, we examined whether dopamine D1 receptor agonists (D1 agonist) and dopamine D2 receptor antagonists (D2 antagonist) or selective ablation of striatal parvalbumin (PV) interneurons could modulate their involuntary movements...

OBJECTIVES: Periodontal diseases are a rather complex problem of modern dentistry and do not have only medical but also social significance. The objective of this study is to weigh the effect of a mixture of Thiotriazoline and L-arginine (1:4) on the parameters of the system of endogenous cytoprotection of blood and periodontal illness in rats with experimental chronic generalized periodontitis and substantiate further study of this blend. MATERIALS AND METHODS: The study aimed to evaluate the impact of a combination of Thiotria-zoline and L-arginine (in a ratio of 1:4) on the parameters of the endogenous blood cytoprotection system and periodontium in rats with experimental chronic generalized periodontitis...

Understanding the mechanisms of drug action in the brain, from the genetic to the neural circuit level, is crucial for the development of new agents that act upon the central nervous system. Determining the brain regions and neurons affected by a drug is essential for revealing its mechanism of action in the brain. c-Fos, a marker of neuronal activation, has been widely used to detect neurons activated by stimuli with high spatial resolution. In this review, the use of c-Fos for the visualization and manipulation of activated neurons is introduced...

Itch is one of the most common clinical symptoms in patients with diseases of the skin, liver, or kidney, and it strongly triggers aversive emotion and scratching behavior. Previous studies have confirmed the role of the prelimbic cortex (Prl) and the nucleus accumbens core (NAcC), which are reward and motivation regulatory centers, in the regulation of itch. However, it is currently unclear whether the Prl-NAcC projection, an important pathway connecting these two brain regions, is involved in the regulation of itch and its associated negative emotions...

ETHNOPHARMACOLOGICAL RELEVANCE: Shentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms. AIM OF THE STUDY: To investigate the effect and potential mechanism of STZYD on neuropathic pain...

Multiple animal models of migraine have been used to develop new therapies. Understanding the transition from episodic (EM) to chronic migraine (CM) is crucial. We established models mimicking EM and CM pain and assessed neuropathological differences. EM and CM models were induced with single NTG or multiple injections over 9 days. Mechanical hypersensitivity was assessed. Immunofluorescence utilized c-Fos, NeuN, and Iba1. Proinflammatory and anti-inflammatory markers were analyzed. Neuropeptides (CGRP, VIP, PACAP, and substance P) were assessed...

Oxidative stress plays a crucial role in the pathogenesis of many diseases. Esculetin is a natural coumarin compound with good antioxidant and anti-inflammatory properties. However, whether esculetin can protect HepG2 cells through inhibiting H2 O2 -induced apoptosis and pyroptosis is still ambiguous. Therefore, this study aimed to investigate the protective effects and mechanisms of esculetin against oxidative stress-induced cell damage in HepG2 cells. The results of this study demonstrate that pretreatment with esculetin could significantly improve the decrease in cell viability induced by H2 O2 and reduce intracellular ROS levels...

Cessation of therapy with a selective serotonin (5-HT) reuptake inhibitor (SSRI) is often associated with an early onset and disabling discontinuation syndrome, the mechanism of which is surprisingly little investigated. Here we determined the effect on 5-HT neurochemistry of discontinuation from the SSRI paroxetine. Paroxetine was administered repeatedly to mice (once daily, 12 days versus saline controls) and then either continued or discontinued for up to 5 days. Whereas brain tissue levels of 5-HT and/or its metabolite 5-HIAA tended to decrease during continuous paroxetine, levels increased above controls after discontinuation, notably in hippocampus...

In recent times, there has been growing attention towards exploring the nutritional and functional aspects of potato protein, along with its diverse applications. In the present study, we examined the anti-osteoclast properties of potato protein hydrolysate (PP902) in vitro. Murine macrophages (RAW264.7) were differentiated into osteoclasts by receptor activator of nuclear factor-κB ligand (RANKL), and PP902 was examined for its inhibitory effect. Initially, treatment with PP902 was found to significantly prevent RANKL-induced morphological changes in macrophage cells, as determined by tartrate-resistant acid phosphatase (TRAP) staining analysis...

Nonunion resulting from early bone resorption is common after bone transplantation surgery. In these patients, instability or osteoporosis causes hyperactive catabolism relative to anabolism, leading to graft resorption instead of fusion. Systemic zoledronate administration inhibits osteoclastogenesis and is widely used to prevent osteoporosis; however, evidence on local zoledronate application is controversial due to osteoblast cytotoxicity, uncontrolled dosing regimens, and local release methods. We investigated the effects of zolendronate on osteoclastogenesis and osteogenesis and explored the corresponding signaling pathways...

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D -driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD...

OBJECTIVE: To investigate the effects and possible mechanisms of negative air ions(NAIs) on blood pressure, oxidative stress, and inflammatory status in spontaneous hypertension rats(SHR). METHODS: A total of 60 SHR(half male and half female) were randomly divided into one-month and three-month groups, 30 rats per groups, based on the duration of the intervention. Each group was further randomized into three groups based on the daily intervention time: SHR control group, 2 h NAIs-SHR group, and 6 h NAIs-SHR group, 10 rats per groups...

This study aims to explore the therapeutic effect and possible mechanisms of icariin in schizophrenia. SD rats were divided into five groups, a control group, a MK801-induced schizophrenia model group, and three icariin treatment groups, with twelve rats in each group. Morris water maze and open field were used to observe the spatial learning and memory ability of rats. Compared with the control group, rats in the MK801-induced model group showed an increase in stereotypic behavior score, distance of spontaneous activities, escape latency, malondialdehyde (MDA) content, and IL-6, IL-1β, TNF-α expression, but a decrease in platform crossing times and superoxide dismutase (SOD) activity (P < 0...

Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics...

Schizophyllan (SPG), a β-glucan from Schizophyllum commune, is recognized for its antioxidant, immunoregulatory, and anticancer activities. In this study, its effects on bone cells, particularly osteoclasts and osteoblasts, were examined. We demonstrated that SPG dose-dependently inhibited osteoclastogenesis and reduced gene expression associated with osteoclast differentiation. SPG also decreased bone resorption and F-actin ring formation. This inhibition could have been due to the downregulation of transcription factors c-Fos and nuclear factor of activated T cells 1 (NFATc1) via the MAPKs (JNK and p38), IκBα, and PGC1β/PPARγ pathways...

BACKGROUND: Electroacupuncture (EA) treatment is efficacious in patients with respiratory disorders, although the mechanisms of its action in lung-function protection are poorly understood. This study aimed to explore the neuroanatomical mechanisms of EA stimulation at the BL13 acupoint (Feishu, EA-BL13) improvement in asthma. METHODS: Allergic asthma was induced by intranasal 2.0% ovalbumin (OVA) instillation combined with intraperitoneal injection of the 10.0% OVA...

The neuronal cell adhesion molecule (NrCAM) is widely expressed and has important physiological functions in the nervous system across the lifespan, from axonal growth and guidance to spine and synaptic pruning, to organization of proteins at the nodes of Ranvier. NrCAM lies at the core of a functional protein network where multiple targets (including NrCAM itself) have been associated with schizophrenia. Here we investigated the effects of chronic unpredictable stress on latent inhibition, a measure of selective attention and learning which shows alterations in schizophrenia, in NrCAM knockout (KO) mice and their wild-type littermate controls (WT)...

Autophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we report a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and brain LC3-interactome reveals roles of neuronal autophagy in targeting proteins of multiple cellular organelles/pathways, including endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) for degradation...

INTRODUCTION: GLP-1 receptor agonists are the number one drug prescribed for the treatment of obesity and type 2 diabetes. These drugs are not, however, without side-effects and in an effort to maximize therapeutic effect while minimizing adverse effects, gut hormone co-agonists received considerable attention as new drug targets in the fight against obesity. Numerous previous reports identified the neuropeptide oxytocin (OXT) as a promising anti-obesity drug. The aim of this study is to evaluate OXT as a possible co-agonist for GLP-1 and examine the effects of its co-administration on food intake (FI) and body weight (BW) in mice...

OBJECTIVE: To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey (dmPAG) in regulating excessive defensive behaviors in mice with post-traumatic stress disorder (PTSD). METHODS: Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno- associated viral vectors (rAAV2/9-CaMKII-mCherry, rAAV2/9-CaMKII-hM3Dq-mCherry and rAAV2/9-CaMKII-hM4Di-mCherry) into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons, followed 2 weeks later by PTSD modeling by single prolonged stress...