Alpha stimulation

The molecular mechanism underlying the promotion of fracture healing by mechanical stimuli remains unclear. The present study aimed to investigate the role of zinc finger protein 36 like 2 (ZFP36L2)-histone deacetylase 1 (HDAC1) axis on the osteogenic responses to moderate mechanical stimulation. Appropriate stimulation of fluid shear stress (FSS) was performed on MC3T3-E1 cells transduced with ZFP36L2 and HDAC1 recombinant adenoviruses, aiming to validate the influence of mechanical stress on the expression of ZFP36L2-HDAC1 and the osteogenic differentiation and mineralization...

BACKGROUND: Mitochondrial dysregulation in skeletal myocytes is considered a major factor in aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target of rapamycin complex 1 (mTORC1) in aged skeletal muscles. METHODS: C2C12 myoblasts were stimulated by 50 μM 7β-hydroxycholesterol (7β-OHC) to observe the changes of DNA damage, mitochondrial membrane potential (Δψm), mitochondrial ROS and PGC-1α protein...

BACKGROUND: Dynamic changes in neuronal activity and in noradrenergic locus coeruleus (LC) projections have been proposed during the transition from acute to chronic pain. Thus, we explored the cellular cFos activity of the LC and its projections, in conjunction with spontaneous pain-like behavior in neuropathic rats. METHODS: Tyrosine hydroxylase:Cre and wild-type Long-Evans rats, males and females, were subjected to chronic constriction injury (CCI) for 2 (short-term, CCI-ST) or 30 days (long-term, CCI-LT), evaluating cFos and Fluoro-Gold expression in the LC, and its projections to the spinal cord (SC) and rostral anterior cingulate cortex (rACC)...

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10-hydroxyoctadecanoic acid ( h 18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h 18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264...

Phytosulfokine-α (PSK-α) is a disulfated pentapeptide (YIYTQ) acting as an intercellular signal peptide and growth factor. It was originally isolated from conditioned medium of asparagus mesophyll cell cultures in 1996 and later characterized as a hormone-like signal molecule with important roles in numerous processes of in vivo plant growth and development. It is currently becoming a valuable mitogenic factor in plant breeding and biotechnology due to its stimulatory effect on in vitro cell elongation, proliferation and differentiation...

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often though surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved two steps: i. four fetuses with indication of surgery were evaluated in three conditions perioperatively: acute pain, rest, and under loud sound stimulation...

Alpha 1 antitrypsin deficiency is a widely under recognized autosomal codominant condition caused by genetic mutations in the SERPINA 1 gene, which encodes for alpha 1 antitrypsin (AAT), a serine protease inhibitor. The SERPINA 1 gene contains 120 variants and mutations in the gene may decrease AAT protein levels or result in dysfunctional proteins. This deficiency leads to unopposed protease activity in tissues, thereby promoting pulmonary and hepatic disease. The most common genotype associated with pulmonary disease is the ZZ genotype, and the most frequent pulmonary manifestation is emphysema...

BACKGROUND: Ketogenic foods limit digestible carbohydrates but contain high fat, and have antioxidant and anti-inflammatory effects as well as improving mitochondrial function. β-Hydroxybutyrate (BHB), 1 of the ketone bodies, reduces the proinflammatory NLR family pyrin domain containing 3 inflammasomes, as well as chemokines in cultures. OBJECTIVES: We assessed the immune-modulating effects of 2 low-carbohydrate (LoCHO) foods varying in protein and fat and compared their effects with a food replete with high-carbohydrate (HiCHO) in healthy canines...

BACKGROUND: Microglial isolation and culturing methods continue to be explored to maximize cellular yield, purity, responsiveness to stimulation and similarity to in vivo microglia. This study aims to evaluate five different microglia isolation methods-three variants of microglia isolation from neonatal mice and two variants of microglia isolation from adult mice-on transcriptional profile and response to HMGB1. METHODS: Microglia from neonatal mice, age 0-3 days (P0-P3) were isolated from mixed glial cultures (MGC)...

Traumatic Brain Injury (TBI) patients frequently experience chronic pain that can enhance their suffering and significantly impair rehabilitative efforts. Clinical studies suggest that damage to the periaqueductal grey matter (PAG) following TBI, a principal center involved in endogenous pain control, may underlie the development of chronic pain. We hypothesized that TBI would diminish the usual pain control functions of the PAG, but that directly stimulating this center using a chemogenetic approach would restore descending pain modulation...

Atherosclerosis is an inflammatory disease of blood vessels involving the immune system. Natural killer T (NKT) cells, as crucial components of the innate and acquired immune systems, play critical roles in the development of atherosclerosis. However, the mechanism and clinical relevance of NKT cells in early atherosclerosis are largely unclear. Our findings demonstrated that there were higher populations of NKT cells and interferon gamma (IFN-γ)-producing NKT cells in the peripheral blood of patients with hyperlipidemia and in the aorta, blood, spleen, and bone marrow of early atherosclerotic mice compared to control groups...

Efferocytosis of apoptotic neutrophils (PMNs) by macrophages is helpful for inflammation resolution and injury repair, but the role of efferocytosis in intrinsic nature of macrophages during septic acute kidney injury (AKI) remains unknown. Here we report that CD47 and signal regulatory protein alpha (SIRPα)-the anti-efferocytotic 'don't eat me' signals-are highly expressed in peripheral blood mononuclear cells (PBMCs) from patients with septic AKI and kidney samples from mice with polymicrobial sepsis and endotoxin shock...

Paediatric functional bladder disorders especially those causing daytime symptoms are a common cause of significant psychosocial and/or physical morbidity and impaired quality of life. Despite the availability of many therapeutic modalities, a significant number of children appear to be refractory to treatment and continue to have symptoms. In this review, we aim to evaluate the current evidence in the use of existing and novel therapeutic options for the management of daytime lower urinary tract disorders in children...

Transcription factor EB (TFEB) is a master regulator of genes involved in the maintenance of autophagic and lysosomal homeostasis, processes which have been implicated in the pathogenesis of GBA-related and sporadic Parkinson's disease (PD), and dementia with Lewy bodies (DLB). TFEB activation results in its translocation from the cytosol to the nucleus. Here, we investigated TFEB subcellular localization and its relation to intracellular alpha-synuclein (aSyn) accumulation in post-mortem human brain of individuals with either incidental Lewy body disease (iLBD), GBA-related PD/DLB (GBA-PD/DLB) or sporadic PD/DLB (sPD/DLB), compared to control subjects...

BACKGROUND: Although macrophages are now recognized as an essential part of the HIV latent reservoir, whether and how viral latency is established and reactivated in these cell types is poorly understood. To understand the fundamental mechanisms of viral latency in macrophages, there is an urgent need to develop latency models amenable to genetic manipulations and screening for appropriate latency-reversing agents (LRAs). Given that differentiated THP-1 cells resemble monocyte-derived macrophages in HIV replication mechanisms, we set out to establish a macrophage cell model for HIV latency using THP-1 cells...

The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conformational states in the absence of ligands; an inactive R state and an active R* state that differ in their affinities for agonists, inverse agonists, and G-protein alpha subunits. The proportion of R* receptors that exist in the absence of agonists determines the level of constitutive receptor activity...

Alpha oscillations have been implicated in time perception, yet a consensus on their precise role remains elusive. This study directly investigates this relationship by examining the impact of alpha oscillations on time perception. Resting-state EEG recordings were used to extract peak alpha frequency (PAF) and peak alpha power (PAP) characteristics. Participants then performed a time generalization task under transcranial alternating current stimulation (tACS) at frequencies of PAF-2, PAF, and PAF+2, as well as a sham condition...

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 ​Hz ("gamma") and lesser power in frequency bands lower than 30 ​Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time...

BACKGROUND: Electroacupuncture (EA) is a promising rehabilitation treatment for upper-limb motor recovery in stroke patients. However, the neurophysiological mechanisms underlying its clinical efficacy remain unclear. This study aimed to explore the immediate modulatory effects of EA on brain network functional connectivity and topological properties. METHODS: The randomized, single-blinded, self-controlled two-period crossover trial was conducted among 52 patients with subacute subcortical stroke...

Human ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins and perform diverse functions. Many of them are associated with multidrug resistance that often results in cancer treatment with poor outcomes. Here, we present the structural bioinformatics study of six human ABC membrane transporters with experimentally determined cryo-electron microscopy (CryoEM) structures including ABCB7, ABCC8, ABCD1, ABCD4, ABCG1, ABCG5, and their AlphaFold2-predicted water-soluble QTY variants...