Becker muscular dystrophy: case report, review of the literature, and analysis of differentially expressed hub genes.

Introduction: Becker muscular dystrophy (BMD) is a genetic and progressive neuromuscular disease caused by mutations in the dystrophin gene with no available cure. A case report and comprehensive review of BMD cases aim to provide important clues for early diagnosis and implications for clinical practice. Genes and pathways identified from microarray data of muscle samples from patients with BMD help uncover the potential mechanism and provide novel therapeutic targets for dystrophin-deficient muscular dystrophies.

Protective effect of gastrodin on peripheral neuropathy induced by anti-tumor treatment with vincristine in rat models.

Cancer is a common disease threatening human health, chemotherapy is widely used in clinical treatment of cancer, but chemotherapy-induced peripheral neuropathy (CIPN) has a relevant impact on life quality of cancer patients. Administration of gastrodin can relieve chronic pain to cancer patients with CIPN and attenuated the inflammatory response by reducing the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, its exact molecular mechanisms remain unclear.

Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer.

Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease.

Clonidine preconditioning improved cerebral ischemia-induced learning and memory deficits in rats via ERK1/2-CREB/ NF-κB-NR2B pathway.

Clonidine, a classical α-2 adrenergic agonists, has been shown to antagonize brain damage caused by hypoxia, cerebral ischemia and excitotoxicity and reduce cerebral infarction volume in recent studies. We herein investigate the regulatory effect and possible underlying mechanism of clonidine on learning and memory in rats with cerebral ischemia. The cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2h and reperfusion for 28 days.

Chronic Rapamycin Treatment Improved Metabolic Phenotype but Inhibited Adipose Tissue Browning in High-Fat Diet-Fed C57BL/6J Mice.

Rapamycin (Rap) has been demonstrated to affect lipid metabolism through stimulating lipolysis, inhibiting de novo lipogenesis and reducing adiposity. In the present study, we investigated rapamycin exposure's influence on adipose tissue browning in high-fat diet-induced fatty mice. Four-week old C57BL/6J mice were fed normal chow or high-fat diet for a period of 6 weeks and then divided into three groups: (1) Nor group: mice fed with normal chow; (2) high fat diet (HFD) group: fatty mice fed with high-fat diet; (3) Rap group: high-fat diet-fed fatty mice treated intragastrically with rapamycin at a dose of 2.

Clonidine preconditioning alleviated focal cerebral ischemic insult in rats via up-regulating p-NMDAR1 and down-regulating NMDAR2A / p-NMDAR2B.

A brain ischemia rat model was established by middle cerebral artery occlusion (MCAO) for 2h and reperfusion for 4h to investigate the underlying mechanism of the neuroprotection action of clonidine, a classical alpha-2 adrenergic agonist, on cerebral ischemia. Clonidine and yohimbine were intraperitoneally given to the rats each day for a week before ischemia. Neurological deficits evaluations were carried out at 6h after operation.

Activation of GABAB2 subunits alleviates chronic cerebral hypoperfusion-induced anxiety-like behaviours: A role for BDNF signalling and Kir3 channels.

Anxiety is an affective disorder that is commonly observed after irreversible brain damage induced by cerebral ischemia and can delay the physical and cognitive recovery, which affects the quality of life of both the patient and family members. However, anxiety after ischemia has received less attention, and mechanisms underlying anxiety-like behaviours induced by chronic cerebral ischemia are under-investigated. In the present study, the chronic cerebral hypoperfusion model was established by the permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) in rats, and anxiety-related behaviours were evaluated.

Baclofen ameliorates spatial working memory impairments induced by chronic cerebral hypoperfusion via up-regulation of HCN2 expression in the PFC in rats.

Chronic cerebral hypoperfusion (CCH) causes memory deficits and increases the risk of vascular dementia (VD) through several biologically plausible pathways. However, whether CCH causes prefrontal cortex (PFC)-dependent spatial working memory impairments and Baclofen, a GABAB receptor agonist, could ameliorate the impairments is still not clear especially the mechanisms underlying the process. In this study, rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH.

Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region.

Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12weeks group, 2VO 4, 8 and 12weeks group.

Enrichment assessment of multiple virtual screening strategies for Toll-like receptor 8 agonists based on a maximal unbiased benchmarking data set.

Toll-like receptor 8 agonists, which activate adaptive immune responses by inducing robust production of T-helper 1-polarizing cytokines, are promising candidates for vaccine adjuvants. As the binding site of toll-like receptor 8 is large and highly flexible, virtual screening by individual method has inevitable limitations; thus, a comprehensive comparison of different methods may provide insights into seeking effective strategy for the discovery of novel toll-like receptor 8 agonists. In this study, the performance of knowledge-based pharmacophore, shape-based 3D screening, and combined strategies was assessed against a maximum unbiased benchmarking data set containing 13 actives and 1302 decoys specialized for toll-like receptor 8 agonists.

Clonidine ameliorates cognitive impairment induced by chronic cerebral hypoperfusion via up-regulation of the GABAR1 and GAD67 in hippocampal CA1 in rats.

Chronic cerebral hypoperfusion may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood. In this study, we investigated whether clonidine, an α-adrenergic receptor agonist, could play neuroprotective role against chronic ischemic brain injury and the potential mechanism. Rats were subjected to permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO).

Imbalance of HCN1 and HCN2 expression in hippocampal CA1 area impairs spatial learning and memory in rats with chronic morphine exposure.

The hyperpolarization-activated cyclic-nucleotide-gated non-selective cation (HCN) channels play a vital role in the neurological basis underlying nervous system diseases. However, the role of HCN channels in drug addiction is not fully understood. In the present study, we investigated the expression of HCN1 and HCN2 subunits in hippocampal CA1 and the potential molecular mechanisms underlying the modulation of HCN channels in rats with chronic morphine exposure with approaches of electrophysiology, water maze, and Western blotting.

Dopamine inhibits excitatory neurotransmission in basolateral amygdala during development via pre-synaptic mechanism.

Objectives: Dopaminergic signaling in the basolateral amygdala (BLA) is important for emotion-related activity. However, little is known about the influence of dopamine (DA) on excitatory synaptic transmission of pyramidal neurons in BLA at early developmental stage. Here in this study, we observed the effect of DA on excitatory neurotransmission in the pyramidal cells of BLA in acute slices.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments.

Cell-penetrating Peptide-mediated therapeutic molecule delivery into the central nervous system.

The blood-brain barrier (BBB), a dynamic and complex barrier formed by endothelial cells, can impede the entry of unwanted substances - pathogens and therapeutic molecules alike - into the central nervous system (CNS) from the blood circulation. Taking into account the fact that CNS-related diseases are the largest and fastest growing unmet medical concern, many potential protein- and nucleic acid-based medicines have been developed for therapeutic purposes. However, due to their poor ability to cross the BBB and the plasma membrane, the above-mentioned bio-macromolecules have limited use in treating neurological diseases.