A5007031430- Pain Mechanisms and Treatments
- Tactile and Sensory Interactions
- Neuroscience and Neural Engineering
- Ion Channels and Receptors
- Muscle activation and electromyography studies
- Ion channel regulation and function
- Urinary Bladder and Prostate Research
- Phytochemicals and Antioxidant Activities
- Dermatology and Skin Diseases
- Nerve Injury and Rehabilitation
- Neurobiology and Insect Physiology Research
- Peripheral Nerve Disorders
- Nerve injury and regeneration
- Metabolism, Diabetes, and Cancer
- Thermoregulation and physiological responses
- Visual perception and processing mechanisms
- EEG and Brain-Computer Interfaces
- Neural dynamics and brain function
- Diabetes Treatment and Management
- Pain Management and Placebo Effect
- Neonatal and Maternal Infections
- Multisensory perception and integration
- Preterm Birth and Chorioamnionitis
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
Tianjin Medical University General Hospital
2024
Johns Hopkins Medicine
2001-2024
Johns Hopkins University
2001-2024
Northwest A&F University
2023
Bristol-Myers Squibb (United States)
2008-2021
The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
2020
Shanghai Stomatological Hospital
2019
China Pharmaceutical University
2015-2018
State Key Laboratory of Natural Medicine
2018
Simcere Pharmaceutical (China)
2009-2015
The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in dose-dependent manner by much 55% hyperglycemic streptozotocin (STZ) rats. These findings, combined with favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment type 2 diabetes.
Ligation and transection of the L5 spinal nerve in rat lead to behavioral signs pain hyperalgesia. Discharge injured nociceptors has been presumed play a role generating pain. However, A fibers, but not C have shown develop spontaneous activity. Moreover, an dorsal root rhizotomy does reverse this behavior, suggesting that signals from other uninjured nerves are involved. We asked if abnormal activity develops adjacent, root. Single fiber recordings were made L4 after ligation nerve. Within...
We demonstrated recently that uninjured C-fiber nociceptors in the L4 spinal nerve develop spontaneous activity after transection of L5 nerve. postulated Wallerian degeneration leads to an alteration properties neighboring, afferents from adjacent nerves. To explore role myelinated versus unmyelinated fibers, we investigated effects ventral rhizotomy rat. This lesion predominantly fibers. Mechanical paw-withdrawal thresholds were assessed with von Frey hairs, and teased-fiber techniques used...
Vanilloids such as capsaicin have algesic properties and seem to mediate their effects via activation of the vanilloid receptor 1 (VR1), a ligand-gated ion channel highly expressed on primary nociceptors. Although blockade capsaicin-induced VR1 has been demonstrated in vitro vivo with antagonist capsazepine, efficacy rat models chronic pain not observed this compound. Here, we describe pharmacology potent antagonist,...
The dried flower head of chrysanthemum is a Chinese medicine, and also used as functional food material. effects different drying processes on the bioactive chemical contents antioxidant activities ‘Xiaobaiju’ ‘Taiju’ were examined. Two kinds harvest materials handled with sun-dried, shade-dried or oven-dried at low, middle high levels. An HPLC (high performance liquid chromatography) method was to simultaneously quantify eight compounds. assayed in vitro. results showed that oven-drying had...
Recent studies have suggested that activity at different 5HT receptor subtypes in the spinal cord either inhibits or facilitates nociceptive processing cord. The present study has examined role of 5HT3 receptors dorsal horn rat Using both behavioural and electrophysiological studies, ligands been applied by a common route (i.e. intrathecal microinjection). In addition, only noxious heat used as form stimulation. Intrathecal injection mCPBG (0.02–0.2 nmol) increased responsiveness neurones to...
The recently cloned vanilloid receptor (VR1) is postulated to account for heat and capsaicin sensitivity in unmyelinated afferents. We sought determine whether also coexist myelinated nociceptive Action potential (AP) activity was recorded from single A-fiber nociceptors that innervated the hairy skin monkey. Before intradermal injection of (10 microg/10 microl) into receptive field, were classified as heat-sensitive (threshold, </=53 degrees C, 1 sec) or heat-insensitive afferents...
In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express receptors these pruritogens, MRGPRD MRGPRX1, respectively, cutaneous afferents pruritogens activate in primate. situ hybridization studies revealed that MRGPRX1 are co-expressed a subpopulation TRPV1+ DRG neurons. electrophysiological recordings nonhuman primates (Macaca...
New series of dipeptidyl boronate inhibitors 20S proteasome were designed and synthesized. The comprehensive understanding the SAR was obtained by utilizing variation four substituents. From screened compounds in enzyme, novel 49 50 identified to be highly potent druglike candidates with IC(50) values 1.2 1.6 nM, respectively, which showed better activities than drug bortezomib on market. Two hematologic human tumor cell lines, HL-60 U266, significantly sensitive both nearly same potency as...
Scutellaria baicalensis Georgi is a traditional Chinese herbal medicine mainly containing flavonoids that contribute to its bioactivities. In this study, the distributions and dynamic changes of flavonoid levels in various organs S. at different development stages were investigated by UHPLC-QTOF-MS/MS HPLC-DAD methods. The results indicated metabolic profiles changed with growth development. During initial germination stage, seeds contained flavonols. With growth, main kinds from flavonols...
An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed from β-amino acids is reported. SAR analysis revealed that bicyclic groups at the R¹ position, 3-F substituents R² and bulky aliphatic R³ position were favorable to activities. Enzymatic screening results showed compound 78, comprising all these features, was most active inhibitor against 20S human less than a 2 nM level, as marketed drug bortezomib. Cellular assays...
A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties previously described lead compounds from piperazinecarboxamide series. The for their ability block capsaicin acid-induced calcium influx CHO cells expressing human TRPV1. most potent these further characterized pharmacokinetic, efficacy, body temperature studies. On the basis its vivo safety, toxicological properties, compound 37 was selected evaluation clinical trials.
Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves.In anesthetized monkey, centrifugal or centripetal recordings were made from single the peroneal sural nerve, electrical stimuli applied either sciatic cutaneous endings, respectively. In recordings, stimulation at chain dorsal root was used...
Agonism of the 5-HT2C receptor represents one most well-studied and clinically proven mechanisms for pharmacological weight reduction. Selectivity over closely related 5-HT2A 5-HT2B receptors is critical as their activation has been shown to lead undesirable side effects major safety concerns. In this communication, we report development a new screening paradigm that utilizes an active site mutant D134A (D3.32) identify atypical agonist structures. We additionally discovery optimization...
Osteoporosis is a prevalent condition among postmenopausal women, and lacks satisfactory therapeutic options. Hydrogen (H2) has been shown to be effective in alleviating many diseases. This study aimed investigate the effects of H2 on inhibiting osteoclastogenesis bone loss ovariectomized mice.Osteoclast differentiation from Raw264.7 cells was induced with receptor activator NF-κB ligand (RANKL) or without 60% H2. The number resorption activity osteocalsts were assessed by tartrate-resistant...
Variations in baseline skin temperature can be encountered experimental and clinical pain states. Such variations have been shown to greatly alter the response radiant heat stimuli when of stimulus is not controlled. We carried out a psychophysical investigation examine influence on ratings temperature-controlled stimuli. A CO2 laser thermal stimulator was used deliver under radiometer feedback control volar forearm. Each consisted 30 s controlled interval (at 34 or 38°C) followed by stepped...