Neurobiological mechanisms of antiallodynic effect of transcranial direct current stimulation (tDCS) in a mice model of neuropathic pain.

Background: Neuropathic pain is relatively common and occurs in approximately 6-8% of the population. It is associated with allodynia and hyperalgesia. Thus, non-pharmacological treatments, such as transcranial direct current stimulation (tDCS) may be useful for relieving pain.

Characterization of alginate/chitosan-based nanoparticles and mathematical modeling of their SpBMP-9 release inducing neuronal differentiation of human SH-SY5Y cells.

The incidence of brain degenerative disease such as Alzheimer's disease (AD) will increase as the world population is ageing. While current AD treatments have only a transient effect, there are many evidences indicating that some growth factors, such as BMP-9, may be used to treat AD. However, growth factors cannot readily access the brain because of their size and the presence of the blood brain barrier.

miR-15b represses BACE1 expression in sporadic Alzheimer's disease.

Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1) is conceived as a potential target for therapies against Alzheimer disease (AD). MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in sporadic AD.

Limax extract ameliorates cigarette smoke-induced chronic obstructive pulmonary disease in mice.

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive and lethal lung disease with few treatments. Limax, a mollusk with lung, has been widely used to control phlegm and cough in China, yet whether Limax has a positive effect on COPD is unknown. This study investigated the effects of water-soluble extract from Limax on COPD development and the underlying mechanisms.

Targeting IL-5Rα with antibody-conjugates reveals a strategy for imaging and therapy for invasive bladder cancer.

Despite the high interest and concern due to an increasing incidence and death rate, patients who develop muscle invasive bladder cancer (MIBC) have few options available. However, the past decade has produced many candidate bladder tumor-specific markers but further development of these markers is still needed for creating effective targeted medications to solve this urgent need. Interleukin-5 receptor α-subunit (IL-5Rα) has recently been reported to be involved in MIBC progression.

Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB Receptors.

The mechanism of action of cannabidiol (CBD), the main non-psychotropic component of L., is not completely understood. First assumed that the compound was acting via cannabinoid CB receptors (CBRs) it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs); however, CBD does not bind with high affinity to the orthosteric site of any GPCR.

Artemisinin: A Panacea Eligible for Unrestrictive Use?

Although artemisinin has been used as anti-malarial drug, accumulating evidence on the extended therapeutic potential of artemisinin emerges. Apart from anti-malaria and anti-tumor, artemisinin can also exert beneficial effects on some metabolic disorders, such as obesity, diabetes, and aging-related diseases. However, whether artemisinin should be applied to treatment of the wide-spectrum diseases is debating.

CDK7 inhibition suppresses rheumatoid arthritis inflammation via blockage of NF-κB activation and IL-1β/IL-6 secretion.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability. Anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARDs) may improve RA process. However, in most patients the treatment effect is still not satisfactory.

Plasminogen kringle 5 suppresses gastric cancer via regulating HIF-1α and GRP78.

Inhibition of tumour angiogenesis has an important role in antitumour therapy. However, a recent study indicates that antiangiogenesis therapy may lead to glucose-related protein 78 (GRP78) associated antiapoptotic resistance. The present study aims to elucidate the dual effects of plasminogen kringle 5 (K5) on tumour angiogenesis and apoptosis induction by targeting hypoxia-inducible factor 1α (HIF-1α) and GRP78.

May Determine Chondroitin Sulfate Ameliorating or Aggravating Osteoarthritis.

Chondroitin sulfate (CS) has shown either ameliorating or aggravating effects on osteoarthritis (OA) in separately conducted clinical trials. Because CS is usually administered orally, it should be affected by or would impact on the individual gut microbiota. Evidence is accumulating that CS can nourish sulfatase-secreting bacteria (SSB) and sulfate-reducing bacteria (SRB).

Screening and identification of potential biomarkers in triple-negative breast cancer by integrated analysis.

Triple-negative breast cancer (TNBC) has attracted great attention due to its unique biology, poor prognosis, and aggressiveness. TNBC patients are more likely to suffer from metastasis. We screened and identified the TNBC-specific genes as potential biomarkers.

Sugemule-3 Protects against Isoprenaline-induced Cardiotoxicity .

Background: Sugemule-3 (SD) is a traditional Chinese medicine with protective effect of myocardium. However, the underlying mechanisms of the effect had not been elucidated.

Materials And Methods: In the present study, the serum of SD was prepared.

Therapeutic potential for leukocyte elastase in chronic pain states harboring a neuropathic component.

Neuropathic pain is an integral component of several chronic pain conditions and poses a major health problem worldwide. Despite emerging understanding of mechanisms behind neuropathic pain, the available treatment options are still limited in efficacy or associated with side effects, therefore making it necessary to find viable alternatives. In a genetic screen, we recently identified SerpinA3N, a serine protease inhibitor secreted in response to nerve damage by the dorsal root ganglion neurons and we showed that SerpinA3N acts against induction of neuropathic pain by inhibiting the T-cell- and neutrophil-derived protease, leucocyte elastase (LE).

A mouse model for pain and neuroplastic changes associated with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest human malignancies and is associated with excruciating pain, which is a serious complication and severely impacts the quality of life in patients. In human patients, poor survival prognosis is linked to remarkable remodeling of intrapancreatic nerves, which, in turn, is correlated to increased pain intensity. Understanding mechanisms underlying pain associated with PDAC has been hampered by the lack of animal models which replicate all germane aspects of the disease and importantly, enable analyses of pain associated with PDAC.

Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups.

miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels.

Pathophysiological mechanisms underlying pain associated with cancer are poorly understood. microRNAs (miRNAs) are a class of noncoding RNAs with emerging functional importance in chronic pain. In a genome-wide screen for miRNAs regulated in dorsal root ganglia (DRG) neurons in a mouse model of bone metastatic pain, we identified miR-34c-5p as a functionally important pronociceptive miRNA.

Optimizing drug development in oncology by clinical trial simulation: Why and how?

In therapeutic research, the safety and efficacy of pharmaceutical products are necessarily tested on humans via clinical trials after an extensive and expensive preclinical development period. Methodologies such as computer modeling and clinical trial simulation (CTS) might represent a valuable option to reduce animal and human assays. The relevance of these methods is well recognized in pharmacokinetics and pharmacodynamics from the preclinical phase to postmarketing.

Alzheimer's Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration of Neurodegeneration from Pro-inflammatory 'Wounding' to Anti-inflammatory 'Healing'.

Objective: The etiological initiators of neuroinflammation remain inconclusive, and effective interventions to block neurodegeneration are unavailable. Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)-like neurodegeneration in mice. CC not only upregulates the cerebral pro-inflammatory cytokines including tumor necrosis factor α (TNF-α) and interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10), an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine.

Ibutilide treatment protects against ER stress induced apoptosis by regulating calumenin expression in tunicamycin treated cardiomyocytes.

Background: Ibutilide, a class III antiarrhythmic agent has been shown to be cardioprotective in treating atrial fibrillation, promoting cardioconversion and recently this agent has been shown to protect against ER stress induced apoptosis in cardiomyocytes. In this study we begin to identify the mechanism by which ibutilide exerts its cardioprotection in tunicamycin treated cardiomyocytes. We examined ER stress markers including calumenin; a calcium binding ER chaperone protein that has recently been linked to ER stress in cardiomyocytes, in our treated cells.

[The correlation research on miRNA378 and calumenin,endoplasmic reticulum stress,apoptosis in suckling mouse myocardial cells infected with coxsackie virus B3].

Objective: To investigate the effects of silencing miRNA378 on apoptosis, endoplasmic reticulum stress and calumenin of cardiomyocyte with coxsackie virus B3 (CVB3) infection.

Methods: Primary cultured suckling mouse myocardium were divided into control group (normal cell), coxsackie virus infection group (normal cell and coxsackie virus B3), miRNA378 control group (normal cell +coxsackie virus B3+miRNA378 empty plasmid), miRNA378 silencing plasmid group(normal cells + coxsackie virus B3 + miRNA378 silencing plasmid). Four groups of cells were transfected, infected and treated in CO incubator at 37℃.

Effect of dyad training on medical students' cardiopulmonary resuscitation performance.

We investigated the effects of dyadic training on medical students' resuscitation performance during cardiopulmonary resuscitation (CPR) training.We provided students with a 2-hour training session on CPR for simulated cardiac arrest. Student teams were split into double groups (Dyad training groups: Groups A and B) or Single Groups.

Genome-Wide Sequencing Reveals MicroRNAs Downregulated in Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCM) are vascular lesions associated with loss-of-function mutations in one of the three genes encoding KRIT1 (CCM1), CCM2, and PDCD10. Recent understanding of the molecular mechanisms that lead to CCM development is limited. The role of microRNAs (miRNAs) has been demonstrated in vascular pathologies resulting in loss of tight junction proteins, increased vascular permeability and endothelial cell dysfunction.

Inhibitory Effect of Hesperetin and Naringenin on Human UDP-Glucuronosyltransferase Enzymes: Implications for Herb-Drug Interactions.

Hesperetin (HET) and naringenin (NGR) are flavanones found in citrus (oranges and grapefruit) and Aurantii Fructus Immaturus. The present study aims to investigate the inhibition potential of HET and NGR derivatives towards one of the most important phase II drug-metabolizing enzymes-uridine diphosphate (UDP)-glucuronosyltransferases (UGTs). We used trifluoperazine as a probe substrate to test UGT1A4 activity, and recombinant UGT-catalyzed 4-methylumbelliferone glucuronidation was used as a probe reaction for other UGT isoforms.