Involvement of ionomic metabolism of both the cerebrospinal fluid and the spinal cord in the analgesic efficacy of matrine in rats.

Context: Matrine has antinociceptive properties, and spinal cord ionomic changes are involved in bone cancer pain.

Objective: To investigate the relationship between ionomic metabolism in cerebrospinal fluid (CSF) and spinal cord and matrine's analgesic efficacy.

Materials And Methods: The antinociceptive effects of matrine were identified in rats intraperitoneal (i.

Contamination and source-specific health risk assessment of soil heavy metals in the middle and upper reaches of the Heihe River Basin of China.

Anthropogenic activities drive heavy metal contamination in soil, making source-specific apportionment essential for managing health risks in rapidly urbanizing areas. This study focuses on the novel task of quantifying health risks from specific sources of heavy metal contamination and visualizing the spatial patterns of human activities' impact on heavy metal contamination and health risks. It combined multiple analytical techniques, including pollution indices, health risk assessments, and bivariate local indicators of spatial association analysis.

Analysis of Ionomic Profiles of Spinal Cords in a Rat Model with Bone Cancer Pain.

Background: Ionomics is used to study levels of ionome in different states of organisms and their correlations. Bone cancer pain (BCP) severely reduces quality of life of patients or their lifespan. However, the relationship between BCP and ionome remains unclear.

Bckdk-Mediated Branch Chain Amino Acid Metabolism Reprogramming Contributes to Muscle Atrophy during Cancer Cachexia.

Scope: Branched chain amino acids (BCAAs) are essential amino acids and important nutrient signals for energy and protein supplementation. The study uses muscle-specific branched-chain α-keto acid dehydrogenase kinase (Bckdk) conditional knockout (cKO) mice to reveal the contribution of BCAA metabolic dysfunction to muscle wasting.

Method And Results: Muscle-specific Bckdk-cKO mice are generated through crossbreeding of Bckdk mice with Myf5 mice.

Store-operated calcium entry mediates hyperalgesic responses during neuropathy.

Neuropathic pain (NP), resulting from nerve injury, alters neural plasticity in spinal cord and brain via the release of inflammatory mediators. The remodeling of store-operated calcium entry (SOCE) involves the refilling of calcium in the endoplasmic reticulum via STIM1 and Orai1 proteins and is crucial for maintaining neural plasticity and neurotransmitter release. The mechanism underlying SOCE-mediated NP remains largely unknown.

D2HGDH-mediated D2HG catabolism enhances the anti-tumor activities of CAR-T cells in an immunosuppressive microenvironment.

The effect of immunotherapy is limited by oncometabolite D-2-hydroxyglutarate (D2HG). D2HGDH is an inducible enzyme that converts D2HG into the endogenous metabolite 2-oxoglutarate. We aimed to evaluate the impairment of CD8 T lymphocyte function in the high-D2HG environment and to explore the phenotypic features and anti-tumor effect of D2HGDH-modified CAR-T cells.

Association Between Peripheral Adiponectin and Lipids Levels and the Therapeutic Response to Donepezil Treatment in Han Chinese Patients With Alzheimer's Disease.

Acetylcholinesterase inhibitors (AChEIs) including donepezil (DNP) are considered to be the most promising therapeutic possibilities of Alzheimer's disease (AD). The response to DNP in AD patients varies and it is valuable to identify the potential markers that can predict the efficacy. Moreover, DNP has been found to affect bone function, but the exact mechanism is still unclear.

Matrine improves skeletal muscle atrophy by inhibiting E3 ubiquitin ligases and activating the Akt/mTOR/FoxO3α signaling pathway in C2C12 myotubes and mice.

Skeletal muscle wasting is a feature of cancer cachexia that increases patient morbidity and mortality. Matrine, the main bioactive component of Sophora flavescens, has been approved for the prevention and therapy of cancer cachexia in China. However, to the best of our knowledge, its mechanism in improving muscle wasting remains unknown.

Intrathecal administration of antioxidants attenuates mechanical pain hypersensitivity induced by REM sleep deprivation in the rat.

Background Sleep deprivation as well as peripheral neuropathy and cutaneous neurogenic inflammation has a facilitatory effect on pain perception. Here we studied whether oxidative stress-related mechanisms in the spinal cord that have been shown to contribute to pain facilitation in peripheral neuropathy and cutaneous neurogenic inflammation play a role in sleep deprivation-induced pain hypersensitivity Methods Flower pot method was used to induce rapid eye movement sleep deprivation (REMSD) of 48 h duration in the rat that had a chronic intrathecal (i.t.

Acetylcholinesterase Inhibitor Donepezil Effects on Plasma β-Hydroxybutyrate Levels in the Treatment of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by a multi-factorial etiology that is not completely understood. Donepezil is a first-line acetylcholinesterase inhibitor used for the treatment of AD that has been found, in addition to its potent acetylcholinesterase inhibitory effect, to act through other non-cholinergic mechanisms such as affecting mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma coactivator (PGC1α). Mitochondrial biogenesis and PGC-1α, at least in part, are associated with hepatic fatty acid oxidation and ketogenesis.

Association between ABCA1 gene polymorphisms and the therapeutic response to donepezil therapy in Han Chinese patients with Alzheimer's disease.

Aim: It is reported that ABCA1, which plays a key role in cholesterol transport and apolipoprotein E (APOE) metabolism in the brain, is related to Alzheimer's disease. However, few studies have focused on the relationship between the ABCA1 gene and the therapeutic response to donepezil (DNP), which has been shown to be related to reduced sAPP production.This study evaluated the association between the ABCA1 gene polymorphism and the clinical response to donepezil therapy in Han Chinese patients with Alzheimer's disease.

Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia.

Background: Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance-based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model.

Characterization of the subcellular localization of Epstein-Barr virus encoded proteins in live cells.

Epstein-Barr virus (EBV) is the pathogenic factor of numerous human tumors, yet certain of its encoded proteins have not been studied. As a first step for functional identification, we presented the construction of a library of expression constructs for most of the EBV encoded proteins and an explicit subcellular localization map of 81 proteins encoded by EBV in mammalian cells. Viral open reading frames were fused with enhanced yellow fluorescent protein (EYFP) tag in eukaryotic expression plasmid then expressed in COS-7 live cells, and protein localizations were observed by fluorescence microscopy.

Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study.

Cardioprotection of dexrazoxane (DZR) against doxorubicin (DOX)-induced cardiotoxicity is contentious and the indicator is controversial. A pairwise comparative metabolomics approach was used to delineate the potential metabolic processes in the present study. Ninety-six BALB/c mice were randomly divided into two supergroups: tumor and control groups.

Adenovirus-mediated expression of orphan nuclear receptor NR4A2 targeting hepatic stellate cell attenuates liver fibrosis in rats.

Liver fibrosis is a wound-healing response characterized with the accumulation of extracellular matrix (ECM). And hepatic stellate cells (HSCs) are the principal cell source of ECM. NR4A2 (Nurr1) is a member of orphan nuclear receptor NR4A family and acts as transcription factor.

Probing the nuclear import signal and nuclear transport molecular determinants of PRV ICP22.

Background: Herpes simplex virus 1 (HSV-1) ICP22 is a multifunctional protein and important for HSV-1 replication. Pseudorabies virus (PRV) ICP22 (P-ICP22) is a homologue of HSV-1 ICP22 and is reported to be able to selectively modify the transcription of different kinetic classes of PRV genes, however, the subcellular localization, localization signal and molecular determinants for its transport to execute this function is less well understood.

Results: In this study, by utilizing live cells fluorescent microscopy, P-ICP22 fused to enhanced yellow fluorescent protein (EYFP) gene was transient expressed in live cells and shown to exhibit a predominantly nucleus localization in the absence of other viral proteins.

Chinese Herbal Medicines as an Adjunctive Therapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Pancreatic cancer is a common malignancy with a high mortality. Most patients present clinically with advanced pancreatic cancer. Moreover, the effect of radiotherapy or chemotherapy is limited.

Identification of molecular determinants for the nuclear import of pseudorabies virus UL31.

Herpes simplex virus 1 (HSV-1) UL31 is a multifunctional protein and important for HSV-1 infection. Pseudorabies virus (PRV) UL31 is a late protein homologous to HSV-1 UL31. Previous studies showed that PRV UL31 is predominantly localized to nucleus, however, the molecular determinants for its nuclear import were unclear to date.

Characterization of the nuclear import and export signals of pseudorabies virus UL31.

The pseudorabies virus (PRV) UL31 protein (pUL31) is a homologue of the herpes simplex virus 1 pUL31, which is a multifunctional protein that is important for HSV-1 infection. However, little is known concerning the subcellular localization signal of PRV UL31. Here, by transfection with a series of PRV UL31 deletion mutants fused to an enhanced yellow fluorescent protein (EYFP) gene, a bipartite nuclear localization signal (NLS) and a PY motif NLS of UL31 were identified and mapped to amino acids (aa) 4 to 20 (RRRLLRRKSSAARRKTL) and aa 21 to 34 (TRAARDRYAPYFAY), respectively.

Cdk5 contributes to inflammation-induced thermal hyperalgesia mediated by the p38 MAPK pathway in microglia.

Background: The mechanisms underlying cyclin-dependent kinase 5 (Cdk5)-mediated thermal hyperalgesia induced by inflammation remain poorly understood. In the present study, we examined thermal hyperalgesia provoked by peripheral injection of complete Freund׳s adjuvant (CFA) to test for Cdk5 signaling in the spinal dorsal horns of rats through the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which is known to function in mediating inflammatory pain.

Methods: We induced the inflammatory pain model by plantar injection of CFA and compared the inhibitory effects of roscovitine and SB203580 on thermal hyperalgesia.