Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development.

Background: Excitation-contraction (E-C) coupling processes become disrupted in heart failure (HF), resulting in abnormal Ca homeostasis, maladaptive structural and transcriptional remodeling, and cardiac dysfunction. Junctophilin-2 (JP2) is an essential component of the E-C coupling apparatus but becomes site-specifically cleaved by calpain, leading to disruption of E-C coupling, plasmalemmal transverse tubule degeneration, abnormal Ca homeostasis, and HF. However, it is not clear whether preventing site-specific calpain cleavage of JP2 is sufficient to protect the heart against stress-induced pathological cardiac remodeling in vivo.

Honokiol alleviates monosodium urate-induced gouty pain by inhibiting voltage-gated proton channels in mice.

Objective: To investigate whether honokiol (HNK) acted as an analgesic in connection with inhibiting the voltage-gated proton channel (Hv1).

Methods: The model of gouty arthritis was induced by injecting monosodium urate (MSU) crystals into the hind ankle joint of mice. HNK was given by intragastric administration.

The role of acid-sensing ion channels in monosodium urate-induced gouty pain in mice.

Acid-sensing ion channels (ASICs) in dorsal root ganglion (DRG) neurons play an important role in inflammatory pain. The objective of this study is to observe the regulatory role of ASICs in monosodium urate (MSU) crystal-induced gout pain and explore the basis for ASICs in DRG neurons as a target for gout pain treatment. The gout arthritis model was induced by injecting MSU crystals into the ankle joint of mice.

Gene Therapy With the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice.

Background: Transcriptional remodeling is known to contribute to heart failure (HF). Targeting stress-dependent gene expression mechanisms may represent a clinically relevant gene therapy option. We recently uncovered a salutary mechanism in the heart whereby JP2 (junctophilin-2), an essential component of the excitation-contraction coupling apparatus, is site-specifically cleaved and releases an N-terminal fragment (JP2NT [N-terminal fragment of JP2]) that translocates into the nucleus and functions as a transcriptional repressor of HF-related genes.

Regulation of TRPV1 channel in monosodium urate-induced gouty arthritis in mice.

Objective: The transient receptor potential vanilloid subtype 1 (TRPV1) channel is considered to play an important regulatory role in the process of pain. The purpose of this study is to observe the change characteristics of TRPV1 channel in MSU-induced gouty arthritis and to find a new target for clinical treatment of gout pain.

Methods: Acute gouty arthritis was induced by injection of monosodium urate (MSU) crystals into the ankle joint of mice.

Aprepitant Inhibits JNK and p38/MAPK to Attenuate Inflammation and Suppresses Inflammatory Pain.

Substance P contributes to the pathogenesis of pain by acting on NK-1R, specialized sensory neurons that detect noxious stimuli. Aprepitant, an antagonist of NK-1R, is widely used to treat chemotherapy-induced nausea and vomiting. In this study, we used LPS-stimulated BV-2 microglia cell line and animal models of inflammatory pain to explore the analgesic effect of aprepitant on inflammatory pain and its underlying mechanism.

Magnolol attenuates inflammatory pain by inhibiting sodium currents in mouse dorsal root ganglion neurons.

Voltage-gated sodium channels are currently recognized as one of the targets of analgesics. Magnolol (Mag), an active component isolated from Magnolia officinalis, has been reported to exhibit analgesic effects. The objective of this study was to investigate whether the analgesic effect of Mag was associated with blocking Na channels.

Epigallocatechin Gallate During Dietary Restriction - Potential Mechanisms of Enhanced Liver Injury.

Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported.

Modulations of Na1.8 and Na1.9 Channels in Monosodium Urate-Induced Gouty Arthritis in Mice.

The aim of the present study was to observe the changes of TTX-R, Na1.8, and Na1.9 Na currents in MSU-induced gouty arthritis mice, and to explore the possibility of Na1.

Small extracellular vesicles deliver TGF-β1 and promote adriamycin resistance in breast cancer cells.

Chemotherapeutic resistance is a major obstacle in the control of advanced breast cancer (BCa). We have previously shown that small extracellular vesicles (sEVs) can transmit adriamycin resistance between BCa cells. Here, we describe that sEV-mediated TGF-β1 intercellular transfer is involved in the drug-resistant transmission.

Small extracellular vesicle-mediated Hsp70 intercellular delivery enhances breast cancer adriamycin resistance.

Adriamycin (ADR) resistance poses a significant challenge for successfully treating breast cancer (BCa). The mechanism underlying intrinsically acquisition of the resistance remains to be fully elucidated. Here, we describe that small extracellular vesicles (sEVs) mediated Hsp70 transfer is implicated in ADR resistance.

Magnolol inhibits sodium currents in freshly isolated mouse dorsal root ganglion neurons.

The voltage-gated sodium channel (VGSC) currents in dorsal root ganglion (DRG) neurons contain mainly TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na currents. Magnolol (Mag), a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, has been well documented to exhibit analgesic effects, but its mechanism is not yet fully understood. The aim of the present study was to investigate whether the antinociceptive effects of Mag is through inhibition of Na currents.

Characteristics of voltage-gated potassium currents in monosodium urate induced gouty arthritis in mice.

Objective: To evaluate the role of K channels in pain following gouty arthritis.

Methods: The model of acute gouty arthritis was induced by monosodium urate (MSU) in mice. The swelling degree was determined by measuring the circumference of the ankle joint.

Inhibition of apoptosis signal-regulating kinase by paeoniflorin attenuates neuroinflammation and ameliorates neuropathic pain.

Background: Neuropathic pain is a serious clinical problem that needs to be solved urgently. ASK1 is an upstream protein of p38 and JNK which plays important roles in neuroinflammation during the induction and maintenance of chronic pain. Therefore, inhibition of ASK1 may be a novel therapeutic approach for neuropathic pain.

Cytokine-mediated therapeutic resistance in breast cancer.

Therapeutic resistance leading to tumor relapse is a major challenge in breast cancer (BCa) treatment. Numerous factors involved in multiple mechanisms promote the development of tumor chemo/radio-resistance. Cytokines/chemokines are important inflammatory factors and highly related to tumorigenesis, metastasis and tumors responses to treatment.

The Distributions of Voltage-Gated K current Subtypes in Different Cell Sizes from Adult Mouse Dorsal Root Ganglia.

Voltage-gated K (K) currents play a crucial role in regulating pain by controlling neuronal excitability, and are divided into transient A-type currents (I) and delayed rectifier currents (I). The dorsal root ganglion (DRG) neurons are heterogeneous and the subtypes of K currents display different levels in distinct cell sizes. To observe correlations of the subtypes of K currents with DRG cell sizes, K currents were recorded by whole-cell patch clamp in freshly isolated mouse DRG neurons.

Functional miRNAs in breast cancer drug resistance.

Owing to improved early surveillance and advanced therapy strategies, the current death rate due to breast cancer has decreased; nevertheless, drug resistance and relapse remain obstacles on the path to successful systematic treatment. Multiple mechanisms responsible for drug resistance have been elucidated, and miRNAs seem to play a major part in almost every aspect of cancer progression, including tumorigenesis, metastasis, and drug resistance. In recent years, exosomes have emerged as novel modes of intercellular signaling vehicles, initiating cell-cell communication through their fusion with target cell membranes, delivering functional molecules including miRNAs and proteins.

Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

Voltage-gated potassium (K) currents, subdivided into rapidly inactivating A-type currents (I ) and slowly inactivating delayed rectifier currents (I ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I and I in concentration-dependent manner.

Lidocaine alleviates morphine tolerance via AMPK-SOCS3-dependent neuroinflammation suppression in the spinal cord.

Background: Morphine tolerance is a clinical challenge, and its pathogenesis is closely related to the neuroinflammation mediated by Toll-like receptor 4 (TLR4). In Chinese pain clinic, lidocaine is combined with morphine to treat chronic pain. We found that lidocaine sufficiently inhibited neuroinflammation induced by morphine and improved analgesic tolerance on the basis of non-affecting pain threshold.

Induction of suppressor of cytokine signaling 3 via HSF-1-HSP70-TLR4 axis attenuates neuroinflammation and ameliorates postoperative pain.

Postoperative pain is a common form of acute pain that, if not managed effectively, can become chronic pain. Evidence has shown that glia, especially microglia, mediate neuroinflammation, which plays a vital role in pain sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6 receptor (IL-6R) have been considered key components in central pain sensitization and neuroinflammation.

ZNF692 promotes proliferation and cell mobility in lung adenocarcinoma.

By analyzing The Cancer Genome Atlas (TCGA) datasets, we discovered that the zinc finger protein 692 (ZNF692) were over-expressed in Lung adenocarcinoma (LUAD) tissues compared to adjacent non-tumor tissues (P < 0.0001). In this study, we investigated the function of ZNF692 in the progression of LUAD.

Exclusion of alternative exon 33 of Ca1.2 calcium channels in heart is proarrhythmogenic.

Alternative splicing changes the Ca1.2 calcium channel electrophysiological property, but the in vivo significance of such altered channel function is lacking. Structure-function studies of heterologously expressed Ca1.

N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases.

The treatment of neuropathic pain remains a clinical challenge because of its unclear mechanisms and broad clinical morbidity. Matrix metalloproteinase (MMP)-9 and MMP-2 have previously been described as key components in neuropathic pain because of their facilitation of inflammatory cytokine maturation and induction of neural inflammation. Therefore, the inhibition of MMPs may represent a novel therapeutic approach to the treatment of neuropathic pain.

Therapeutic effects of traditional Chinese medicine in patients with symptomatic cervical ectopy.

Purpose: The aim of this study is to evaluate the treatment and efficacy of Badushengjigao, a traditional Chinese medicine (TCM) formula, for symptomatic cervical ectopy.

Method: A patient self-selected two group comparison study was performed. One hundred patients with symptomatic cervical ectopy admitted to the Central Hospital of E-Zhou (Hubei, China) between July 2013 and July 2014 were enrolled in the study.

Activation of Adenosine Monophosphate-activated Protein Kinase Suppresses Neuroinflammation and Ameliorates Bone Cancer Pain: Involvement of Inhibition on Mitogen-activated Protein Kinase.

Background: Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception and the attenuation of morphine antinociceptive tolerance. In this study, the authors investigated the impact of AMPK activation through resveratrol treatment on bone cancer pain.

Methods: The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in rats (n = 8).