Studies of Release Activity in DRGs of Rats with Spared Nerve Injury (SNI) Using YO-PRO-1.

We report a new method for examining changes in membrane permeability in dorsal root ganglion (DRG) cells under peripheral nerve injury conditions. By intravenously injecting YO-PRO-1, a monomeric cyanine nucleic acid stain, into rats with spared nerve injury (SNI), we observed the uptake of YO-PRO-1 in injured neurons and surrounding non-neuronal cells. This approach provides a tool for detecting in vivo DRG cell release activity in intact animals.

Activation of bitter taste receptor TAS2R4 alleviates diabetic nephropathy in mice.

Activation of bitter taste receptor member 4 (TAS2R4) signaling alleviates podocyte injury caused by chronic high glucose; however, whether TAS2R4 activation in podocytes can improve diabetic nephropathy (DN) is to be verified. This study aims to confirm the beneficial effects of quinine, a dual human and rodent TAS2R4 agonist, and matrine with a potent anti-inflammatory activity and binding with TAS2R4 via online prediction and receptor docking on DN in vivo and in vitro. In this study, we found that quinine and matrine markedly ameliorated renal dysfunction, as evidenced by decreases in creatinine and urea nitrogen levels in plasma as well as protein excretion in urine, increased podocyte slit diaphragm and adaptor proteins including Nephrin, Podocin, and Zonula occluden 1, and suppressed activations of NF-κB and the NLRP3 inflammasome in the kidney of DN mice.

Lactate-triggered histone lactylation contributes to podocyte epithelial-mesenchymal transition in diabetic nephropathy in mice.

Diabetic nephropathy (DN) closely relates to morphological and functional changes of podocytes, and anaerobic glycolysis represents the predominant energy source of podocytes. However, it is unknown whether lactate accumulation in chronic high glucose causes epithelial-mesenchymal transition (EMT) of podocytes through lactate-derived histone lysine lactylation (HKla). Lactate levels increased in high glucose-stimulated mouse podocyte cell line MPC and blood and the kidney of diabetic mice.

Novel Compound HJC0416 Attenuates Hepatic Fibrosis via HSP90/NF-κB-Associated Mechanism.

Introduction: Chronic liver disease is driven by a prolonged wound healing response leading to fibrogenesis, potentially progressing to cirrhosis. Hepatic stellate cells (HSCs) are the primary cells driving hepatic fibrosis because they are major producers of extracellular matrix. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ΚB) pathway is a key regulator of inflammatory signaling, and survival of activated HSCs has been found to be NF-KB dependent.

Activation of TAS2R4 signaling attenuates podocyte injury induced by high glucose.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C β2 (PLCβ2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCβ2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells.

Novel Oridonin Analog CYD0682 Inhibits Hepatic Stellate Cell Activation via the Heat Shock Protein 90-Dependent STAT3 Pathway.

Introduction: Activated hepatic stellate cells (HSCs) are the primary effector cells in hepatic fibrosis, over depositing extracellular matrix (ECM) proteins. Our previous work found oridonin analog CYD0682 attenuates proliferation, Transforming Growth Factor β (TGFβ)-induced signaling, and ECM production in immortalized HSCs. The underlying mechanism behind these reductions is unclear.

Volatile Dimethyl Disulfide from Guava Plants Regulate Developmental Performance of Asian Citrus Psyllid through Activation of Defense Responses in Neighboring Orange Plants.

Intercropping with guava ( L.) can assist with the management of Asian citrus psyllid (ACP, Kuwayama), the insect vector of the huanglongbing pathogen, in citrus orchards. Sulfur volatiles have a repellent activity and physiological effects, as well as being important components of guava volatiles.

Volatile Signals From Guava Plants Prime Defense Signaling and Increase Jasmonate-Dependent Herbivore Resistance in Neighboring Citrus Plants.

Intercropping can reduce agricultural pest incidence and represents an important sustainable alternative to conventional pest control methods. Citrus intercropped with guava ( L.) has a lower incidence of Asian citrus psyllid (ACP, Kuwayama) and huanglongbing disease (HLB), but the mechanisms are still unknown.

Full recovery after prolonged resuscitation in a pediatric patient due to fulminant myocarditis: a case report with three-year follow-up.

Background: Fulminant myocarditis (FM) is a common life-threatening disease in pediatric patients, which can result in sudden cardiac arrest (CA). Whether prolonged cardiopulmonary resuscitation (CPR) is beneficial to FM induced CA is unknown.

Case Presentation: We reported the case of an 8-year-old child with FM.

HJC0416 Attenuates Fibrogenesis in Activated Hepatic Stellate Cells via STAT3 and NF-κB Pathways.

Background: Hepatic fibrosis is wound-healing response that is the result of hepatic stellate cell (HSC) activation and subsequent excess extracellular matrix deposition. HSCs can be activated by a variety of inflammatory stimuli as well as through the signal transducer and activator of transcription 3 (STAT3) pathway. HJC0416 is a novel, orally bioavailable small-molecule inhibitor of STAT3 that was developed by our team using a fragment-based drug design approach.

Burn-Induced Impairment of Ileal Muscle Contractility Is Associated with Increased Extracellular Matrix Components.

Introduction: Severe burns lead to marked impairment of gastrointestinal motility, such as delayed gastric emptying and small and large intestinal ileus. However, the cellular mechanism of these pathologic changes remains largely unknown.

Methods: Male Sprague Dawley rats approximately 3 months old and weighing 300-350 g were randomized to either a 60% total body surface area full-thickness scald burn or sham procedure and were sacrificed 24 h after the procedure.

Electroacupuncture downregulates P2X3 receptor expression in dorsal root ganglia of the spinal nerve-ligated rat.

Electroacupuncture has been shown to effectively reduce chronic pain in patients with nerve injury. The underlying mechanisms are not well understood. Accumulated evidence suggests that purinergic P2X3 receptors (P2X3Rs) in dorsal root ganglion neurons play a major role in mediating chronic pain associated with nerve injury.

Toxicity and biochemical effects of itol A on the brown planthopper, Nilaparvata lugens (Stål) (Hemiptera: Delphacidae).

Itol A, a novel isoryanodane diterpene derived from Itoa orientalis Hemsl., has potent activities against insect pests. This study was conducted to determine the contact toxicity and biochemical effects of itol A on the Nilaparvata lugens.

Inflammation induces Epac-protein kinase C alpha and epsilon signaling in TRPV1-mediated hyperalgesia.

The exchange proteins activated by cAMP (Epacs) have been shown to play important roles in producing inflammation-induced nociception. Transient receptor potential vanilloid type 1 (TRPV1) is a major receptor processing thermal and chemosensitive nociceptive information. The role of Epacs in modulating the activity of TRPV1 has yet to be determined.

Application of the combination index (CI)-isobologram equation to research the toxicological interactions of clothianidin, thiamethoxam, and dinotefuran in honeybee, Apis mellifera.

Due to complex pest control scenarios and the needs of agricultural production, different neonicotinoids may be used in certain agricultural applications. Consequently, honeybees may be exposed to these substances through distribution throughout plant tissues via the vascular system through several pathways, such as surface water, the exudates excreted from plants, and air pollution via drift of dust as well as contaminated pollen and nectar. In the current study, the single and combined toxicity of clothianidin, dinotefuran, and thiamethoxam to honeybees was examined after 48 h exposure by the acute oral method and combination index (CI)-isobologram equation.

Epac and Nociceptor Sensitization.

Primary sensory neurons are responsible for transmitting sensory information from the peripheral to the central nervous system. Their responses to incoming stimulation become greatly enhanced and prolonged following inflammation, giving rise to exaggerated nociceptive responses and chronic pain. The inflammatory mediator, prostaglandin E2 (PGE2), released from the inflamed tissue surrounding the terminals of sensory neurons contributes to the abnormal pain responses.

EXPRESS: F-actin links Epac-PKC signaling to purinergic P2X3 receptors sensitization in dorsal root ganglia following inflammation.

Sensitization of purinergic P2X3 receptors (P2X3Rs) contributes to the production of exaggerated nociceptive responses following inflammatory injury. We showed previously that prostaglandin E2 (PGE2) potentiates P2X3R-mediated ATP currents in dorsal root ganglion neurons isolated from both control and complete Freund’s adjuvant-induced inflamed rats. PGE2 potentiation of ATP currents depends only on PKA signaling in control neurons, but it depends on both PKA and PKC signaling in inflamed neurons.

Epac-protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation.

Sensitization of purinergic P2X3 receptors (P2X3Rs) is a major mechanism contributing to injury-induced exaggerated pain responses. We showed in a previous study that cyclic adenosine monophosphate (cAMP)-dependent guanine nucleotide exchange factor 1 (Epac1) in rat sensory dorsal root ganglia (DRGs) is upregulated after inflammatory injury, and it plays a critical role in P2X3R sensitization by activating protein kinase C epsilon (PKCε) inside the cells. protein kinase C epsilon has been established as the major PKC isoform mediating injury-induced hyperalgesic responses.

Identification of dysregulated pathways associated with pancreatic cancer by survival analysis.

In order to identify the dysregulated pathways associated with pancreatic cancer, the fourth leading cause of cancer mortality in the United States, tumor and non-tumor samples were systematically analyzed in the present study. Initially, dysregulated genes in pancreatic cancer were identified using paired t-test. Subsequently, dysregulated biological pathways involved in the development of pancreatic cancer were identified by enrichment analysis.

Analgesic tolerance of opioid agonists in mutant mu-opioid receptors expressed in sensory neurons following intrathecal plasmid gene delivery.

Background: Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mutation have not been fully explored due to the complexity in studies of mutant receptors in vivo.

Communication between neuronal somata and satellite glial cells in sensory ganglia.

Studies of the structural organization and functions of the cell body of a neuron (soma) and its surrounding satellite glial cells (SGCs) in sensory ganglia have led to the realization that SGCs actively participate in the information processing of sensory signals from afferent terminals to the spinal cord. SGCs use a variety ways to communicate with each other and with their enwrapped soma. Changes in this communication under injurious conditions often lead to abnormal pain conditions.

Evaluation of in vivo antioxidant and immunity enhancing activities of sodium aescinate injection liquid.

Oxidative stress is involved in the development and progression of disease. Because sodium aescinate has been reported to have immunity enhancing and antioxidative effects, we investigated its activity by employing a hepatocellular carcinoma (HCC) mouse model. Sixty BALB/c mice were randomly divided into four groups, including a 1.

[Determination of three sweeteners in vinegars by solid phase extraction-high performance liquid chromatography/tandem mass spectrometry].

A solid phase extraction-high performance liquid chromatography/electrospray ionization-tandem mass spectrometry (SPE-HPLC/ESI-MS/MS) method for the determination of 3 sweeteners (acesulfame (AK), sodium saccharin (SA), sodium cyclamate (SC)) in vinegars has been developed. The sample was diluted with acidic water, then purified and enriched with a weak anion exchange SPE column. The HPLC separation was performed on a Pursuit C18 column (150 mm x 2.

Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons.

Purinergic ionotropic P2X7 receptors (P2X7Rs) are closely associated with excitotoxicity and nociception. Inhibition of P2X7R activation has been considered as a potentially useful strategy to improve recovery from spinal cord injury and reduce inflammatory damage to trauma. The physiological functions of P2X7Rs, however, are poorly understood, even though such information is essential for making the P2X7R an effective therapeutic target.