Quanty-cFOS, a Novel ImageJ/Fiji Algorithm for Automated Counting of Immunoreactive Cells in Tissue Sections.

Analysis of neural encoding and plasticity processes frequently relies on studying spatial patterns of activity-induced immediate early genes' expression, such as . Quantitatively analyzing the numbers of cells expressing the Fos protein or mRNA is a major challenge owing to large human bias, subjectivity and variability in baseline and activity-induced expression. Here, we describe a novel open-source ImageJ/Fiji tool, called 'Quanty-cFOS', with an easy-to-use, streamlined pipeline for the automated or semi-automated counting of cells positive for the Fos protein and/or mRNA on images derived from tissue sections.

Lower sertraline plasma concentration in patients co-medicated with clozapine-Implications for pharmacological augmentation strategies in schizophrenia.

Augmentation of antipsychotic treatment with antidepressants represents a common and beneficial treatment strategy in patients suffering from schizophrenia. Combining clozapine and the selective serotonin reuptake inhibitor (SSRI) sertraline represents a clinically important strategy in patients with therapy-resistant schizophrenia, but there is limited knowledge about mutual pharmacokinetic interactions. In the present study, we assessed the impact of clozapine on sertraline plasma concentrations.

Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells.

Ethnopharmacological Relevance: Shengmai formula (SMF) is a well-known Chinese herbal compound preparation, which is utilized extensively for the treatment of myocardial ischemia, arrhythmia and other life-threatening conditions. Our previous researches have shown that some of the active ingredients in SMF can interact with organic anion transport polypeptide 1B1 (OATP1B1), breast cancer resistance protein (BCRP) and organic anion transporter 1 (OAT1), etc. Organic cation transporter 2 (OCT2) is a highly expressed uptake transporter in the kidney, and its interaction with the major active components in SMF remains unclear.

Environmental signals perceived by the brain abate pro-metastatic monocytes by dampening glucocorticoids receptor signaling.

While positive social-behavioral factors predict longer survival in cancer patients, the underlying mechanisms are unknown. Since tumor metastasis are the major cancer mortality factor, we investigated how an enriched environment (EE) conductive to enhanced sensory, cognitive and motor stimulation impact metastatic progression in lungs following intravasation in the circulation. We find that mice housed in EE exhibited reduced number of lung metastatic foci compared to control mice housed in a standard environment (SE).

Layer-specific pain relief pathways originating from primary motor cortex.

The primary motor cortex (M1) is involved in the control of voluntary movements and is extensively mapped in this capacity. Although the M1 is implicated in modulation of pain, the underlying circuitry and causal underpinnings remain elusive. We unexpectedly unraveled a connection from the M1 to the nucleus accumbens reward circuitry through a M1 layer 6-mediodorsal thalamus pathway, which specifically suppresses negative emotional valence and associated coping behaviors in neuropathic pain.

Nrf2 and its dependent autophagy activation cooperatively counteract ferroptosis to alleviate acute liver injury.

Ferroptosis has been implicated in the pathophysiological progression of a variety of diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant response and can counteract ferroptosis by inducing autophagy and targeting genes involved in iron metabolism and glutathione (GSH) synthesis/metabolism. This study investigated how Nrf2 and autophagy interact to prevent ferroptosis in acute liver injury under sulforaphane (SFN) intervention.

NRF2 and FXR dual signaling pathways cooperatively regulate the effects of oleanolic acid on cholestatic liver injury.

Background: Previous studies have shown that the anti-cholestatic effect of oleanolic acid (OA) is associated with FXR and NRF2. However, how the two signaling pathways cooperate to regulate the anti-cholestatic effect of OA remains unclear.

Purpose: This study aimed to further demonstrate the effect of OA on alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury and the interaction mechanism between NRF2 and FXR signaling pathways in maintaining bile acid homeostasis.

Prolonged Suppression of Neuropathic Hypersensitivity upon Neurostimulation of the Posterior Insula in Mice.

Neurostimulation-based therapeutic approaches are emerging as alternatives to pharmacological drugs, but need further development to optimize efficacy and reduce variability. Despite its key relevance to pain, the insular cortex has not been explored in cortical neurostimulation approaches. Here, we developed an approach to perform repetitive transcranial direct current stimulation of the posterior insula (PI tDCS) and studied its impact on sensory and aversive components of neuropathic pain and pain-related anxiety and the underlying neural circuitry in mice using behavioral methods, pharmacological interventions and the expression of the activity-induced gene product, Fos.

The likelihood approach for potential role of "GABRG2 (C588T, C315T) gene polymorphisms" on the poor response to carbamazepine therapy in Pakhtun population of Pakistan.

Background: Gamma-aminobutyric acid A receptor, gamma 2 gene (GABRG2) encode the GABAA receptor which is responsible for fast neuronal inhibition. Polymorphisms in GABGR2 gene affect the clinical response of anti-epileptic drugs (AEDs). Therefore, we carried out an updated study to find the association GABRG2 gene polymorphisms with carbamazepine (CBZ) non-responsive therapy in the Pakhtun population.

Resveratrol reverses TGF-β1-mediated invasion and metastasis of breast cancer cells via the SIRT3/AMPK/autophagy signal axis.

Resveratrol (Resv) has antitumorigenic and antimetastatic activities; however, the molecular mechanisms underlying the inhibitory effects of Resv on the invasion and metastasis of breast cancer cells are still a subject of debate. In our study, we demonstrated that Resv inhibited tumor cell proliferation and tumor growth. It also suppressed invasion and pulmonary metastasis of breast cancer by reversing the transforming growth factor beta 1 (TGF-β1)-mediated EMT process.

Genetic Mouse Models to Study Pancreatic Cancer-Induced Pain and Reduction in Well-Being.

In addition to the poor prognosis, excruciating abdominal pain is a major challenge in pancreatic cancer. Neurotropism appears to be the underlying mechanism leading to neuronal invasion. However, there is a lack of animal models suitable for translationally bridging in vitro findings with clinical trials.

Synthesis and cytotoxic activity of ethyl ferulate derivatives as potent anti-inflammatory agents.

While a range of pharmacological agents are currently used to alleviate inflammation, the clinical administration of many of these anti-inflammatory drugs is associated with high rates of adverse side effects that make them poorly suited to long-term use. Therefore, there is a critical need for the development of novel anti-inflammatory agents. Natural compounds and derivatives like ethyl ferulate have risen to prominence as a foundation for many drug discovery efforts owing to their structural diversity and wide-ranging biological activities.

Cholinergic basal forebrain nucleus of Meynert regulates chronic pain-like behavior via modulation of the prelimbic cortex.

The basal nucleus of Meynert (NBM) subserves critically important functions in attention, arousal and cognition via its profound modulation of neocortical activity and is emerging as a key target in Alzheimer's and Parkinson's dementias. Despite the crucial role of neocortical domains in pain perception, however, the NBM has not been studied in models of chronic pain. Here, using in vivo tetrode recordings in behaving mice, we report that beta and gamma oscillatory activity is evoked in the NBM by noxious stimuli and is facilitated at peak inflammatory pain-like behavior.

Protecting against summation of pain.

Temporal summation in the spinal cord is linked to pathological pain. In a translational genetic association study in this issue of Neuron, Trendafilova et al. (2022) identify the sodium-calcium exchanger 3 as a negative regulator of temporal summation and hypersensitivity via its modulation of calcium homeostasis.

A multiomics and network pharmacological study reveals the neuroprotective efficacy of Fu-Fang-Dan-Zhi tablets against glutamate-induced oxidative cell death.

Neuroprotective therapy after ischemic stroke remains a significant need, but current measures are still insufficient. The Fu-Fang-Dan-Zhi tablet (FFDZT) is a proprietary Chinese medicine clinically employed to treat ischemic stroke in the recovery period. This work aims to systematically investigate the neuroprotective mechanism of FFDZT.

Surgical treatment was desirable to improve neuromuscular function in patients with sustained 3 years fracture-dislocation of lower cervical spine: A case report.

To investigate the changes in neuromuscular function of anterior approach combined with subtotal vertebral body resection and titanium mesh cage (TMC) internal fixation for the old fracture-dislocated lower cervical spine. A 56-year-old female was admitted to the hospital with neck pain and numbness of the left upper extremity for 3 years due to a fall injury from a height, which worsened for 20 days. Although 3 years had passed, the patient still had significant left limb numbness and decreased muscle strength.

CircUBR5 acts as a ceRNA for miR-1179 to up-regulate UBR5 and to promote malignancy of triple-negative breast cancer.

UBR5 is an E3 ubiquitin ligase and an oncogene in a panel of human cancers. However, little is known on its impacts in triple-negative breast cancer (TNBC) and even less on its relationship to circUBR5 (hsa_circ_0001819), a circular RNA derived from exons 2, 3, 4, and 5 of UBR5 gene. In this study, we detected higher expressions of both circUBR5 and UBR5 in TNBC tissues, which were associated with worse prognosis, and also in a panel of breast cancer cells, particularly in TNBC cells.

Interaction of the main active components in Shengmai formula mediated by organic anion transporter 1 (OAT1).

Ethnopharmacological Relevance: Shengmai formula (SMF) is a classical traditional Chinese medicine prescription, which is widely used in the treatment of cardiovascular and cerebrovascular diseases. Our previous studies have demonstrated that some components in SMF can interact with each other through breast cancer resistance protein, sodium taurocholate co-transporting polypeptide, organic anion transporting polypeptide 1B1 and 1B3. Organic anion transporter 1 (OAT1) is highly expressed in kidney, mediating the elimination of many endogenous and exogenous substances.

A systematic analysis of prostaglandin E type 3 receptor isoform signaling reveals isoform- and species-dependent L798106 Gα-biased agonist responses.

Prostaglandins are bioactive lipids involved in many physiological and pathophysiological conditions, such as pain, atherosclerosis, type II diabetes, and parturition. Prostaglandin E (PGE) activates four G protein-coupled receptors (GPCRs), named the PGE types 1-4 receptors (EP1-4), to elicit the intracellular signaling responsible for their physiological actions. There are more than twelve EP3 isoforms in humans that differ only by the sequence of their C-termini.

Extracellular vesicles derived from human bone marrow mesenchymal stem cells protect rats against acute myocardial infarction-induced heart failure.

Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stem cells (BMSCs) are suggested to promote angiogenesis in a rat model of acute myocardial infarction (AMI). This study aimed to explore the underlying mechanism of BMSCs-EVs in AMI-induced heart failure (HF). BMSCs were isolated and verified, and EVs were purified and identified.

Impact of Pharmaceutical Compounds in the Bioremediation of Municipal Biosolids by the White-Rot-Fungi .

The potential of microorganisms for the treatment of municipal biosolids is continuously growing. The present studies evaluated the potency of for the reduction in biosolid mass, production of extracellular enzymes, and removal of pharmaceutical compounds (PhACs) in biosolid slurry in the presence and absence of spiked PhACs [5 non-steroidal anti-inflammatories (NSAIs) and 2 psychoactive compounds (PACs)]. Toxicity after 35 days of fungal treatment was also assessed.

Therapeutic drug level of tacrolimus causing intracranial hemorrhage in a patient with renal transplant.

Tacrolimus is used in solid organ transplant patients to prevent rejection, and no case of intracerebral hemorrhage (ICH) has been reported till date. We report a case of 31-year-old man with diabetes and hypertension for ten years who had a renal transplant four years back; diagnosed with tacrolimus-induced ICH.

Panaxytriol upregulates CYP3A4 expression based on the interaction of PXR, CAR, HSP90α, and RXRα.

Background: Cytochrome P450 3A4 (CYP3A4) is one of the most important drug-metabolizing enzymes in the human body, mainly existing in the liver, small intestine, and kidney. Panaxytriol is one of the key active components in red ginseng and Shenmai injection. Our previous study demonstrated that panaxytriol regulates CYP3A4 expression mainly by activating pregnancy X receptor (PXR).

Preclinical Evaluation of BMP-9-Treated Human Bone-like Substitutes for Alveolar Ridge Preservation following Tooth Extraction.

The success of dental implant treatment after tooth extraction is generally maximized by preserving the alveolar ridge using cell-free biomaterials. However, these treatments can be associated with inflammatory reactions, leading to additional bone volume loss hampering dental implant positioning. Our group developed a self-assembled bone-like substitute constituted of osteogenically induced human adipose-derived stromal/stem cells (hASCs).