Carneyfrancis3822

Chemotherapy-induced neuropathic pain (CINP) is among the most common clinical complications associated with the use of anti-cancer drugs. CINP occurs in nearly 68.1% of the cancer patients receiving chemotherapeutic drugs. Most of the clinically available analgesics are ineffective in the case of CINP patients as the pathological mechanisms involved with different chemotherapeutic drugs are distinct from each other. CINP triggers the somatosensory nervous system, increases the neuronal firing and activation of nociceptive mediators including transient receptor protein vanilloid 1 (TRPV1). TRPV1 is widely present in the peripheral nociceptive nerve cells and it has been reported that the higher expression of TRPV1 in DRGs serves a critical role in the potentiation of CINP. The therapeutic glory of TRPV1 is well recognized in clinics which gives a promising insight into the treatment of pain. But the adverse effects associated with some of the antagonists directed the scientists towards RNA interference (RNAi), a tool to silence gene expression. Thus, ongoing research is focused on developing small interfering RNA (siRNA)-based therapeutics targeting TRPV1. GSK-3 activation In this review, we have discussed the involvement of TRPV1 in the nociceptive signaling associated with CINP and targeting this nociceptor, using siRNA will potentially arm us with effective therapeutic interventions for the clinical management of CINP.Vascular inflammation is one of the main activating stimuli of cardiovascular disease and its uncontrolled development may worsen the progression and prognosis of these pathologies. Therefore, the search for new therapeutic options to treat this condition is undoubtedly needed. In this regard, it may be better to repurpose endogenous anti-inflammatory compounds already known, in addition to synthesizing new compounds for therapeutic purposes. It is well known that vitamin D, anandamide, and melatonin are promising endogenous substances with powerful and wide-spread anti-inflammatory properties. Currently, the epigenetic mechanisms underlying these effects are often unknown. This review summarizes the potential epigenetic mechanisms by which vitamin D, anandamide, and melatonin attenuate vascular inflammation. This information could contribute to the improvement in the therapeutic management of multiple pathologies associated with blood vessel inflammation, through the pharmacological manipulation of new target sites that until now have not been addressed.Our goal was to explore the detrimental impacts of ciprofloxacin (CPFX) and tetracycline (TETRA) on human retinal Müller (MIO-M1) cells in vitro. Cells were exposed to 30, 60 and 120 μg/ml of CPFX and TETRA. The cellular metabolism was measured with the MTT assay. The JC-1 and CM-H2DCFDA assays were used to evaluate the levels of mitochondrial membrane potential (MMP) and ROS (reactive oxygen species), respectively. Mitochondrial DNA (mtDNA) copy number, along with gene expression levels associated with apoptotic (BAX, BCL2-L13, BCL2, CASP-3 and CASP-9), inflammatory (IL-6, IL-1β, TGF-α, TGF-β1 and TGF-β2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4) were analyzed via Quantitative Real-Time PCR (qRT-PCR). Bioenergetic profiles were measured using the Seahorse® XF Flux Analyzer. Cells exposed 24 h to 120 μg/ml TETRA demonstrated higher cellular metabolism compared to vehicle-treated cells. At each time points, (i) all TETRA concentrations reduced MMP levels and (ii) ROS levels were reduced by TETRA 120oroquinolones and tetracyclines on mitochondrial behavior of human retinal MIO-M1 cells.The gut microbiota is a complex ecosystem that inhabits the gastrointestinal tract and consists of archaea, fungi, viruses, and bacteria, with bacteria being dominant. From birth onwards, it coevolves dynamically together with the host. The composition of the gut microbiota is under the influence of a complex interplay between both host and environmental factors. Scientific advances in the past few decades have shown that it is essential in maintaining homeostasis and tipping the balance between health and disease. In addition to its role in food digestion, the gut microbiota is implicated in regulating multiple physiological processes in the host gut mucosa and in distant organs such as the brain. Persistent imbalance between gut microbial communities, termed "dysbiosis," has been associated with several inflammatory and metabolic diseases as well as with central nervous system disorders. In this review, we present the state of the art of current knowledge on an emerging concept, the microbiota-retina axis, and the potential role of its disturbance in the development of retinopathies. We also describe several microbiota-targeting strategies that could constitute preventive and therapeutic tools for retinopathies.The parasubthalamic nucleus (PSTN), a small nucleus located on the lateral edge of the posterior hypothalamus, has emerged in recent years as a highly interconnected node within the network of brain regions sensing and regulating autonomic function and homeostatic needs. Furthermore, the strong integration of the PSTN with extended amygdala circuits makes it ideally positioned to serve as an interface between interoception and emotions. While PSTN neurons are mostly glutamatergic, some of them also express neuropeptides that have been associated with stress-related affective and motivational dysfunction, including substance P, corticotropin-releasing factor, and pituitary adenylate-cyclase activating polypeptide. PSTN neurons respond to food ingestion and anorectic signals, as well as to arousing and distressing stimuli. Functional manipulation of defined pathways demonstrated that the PSTN serves as a central hub in multiple physiologically relevant networks and is notably implicated in appetite suppression, conditioned taste aversion, place avoidance, impulsive action, and fear-induced thermoregulation. We also discuss the putative role of the PSTN in interoceptive dysfunction and negative urgency. This review aims to synthesize the burgeoning preclinical literature dedicated to the PSTN and to stimulate interest in further investigating its influence on physiology and behavior.Pioglitazone, an agonist at peroxisome proliferator-activated receptor gamma, is FDA-approved for the treatment of insulin resistance in type 2 diabetes. Numerous studies in male rodents suggest that pioglitazone inhibits inflammatory and neuropathic pain, but few included female subjects. To address this gap, we compared the effects of pioglitazone in both sexes in the intraplantar methylglyoxal model (MG) model of chemical pain and painful diabetic neuropathy (PDN), the plantar incision model (PIM) of postoperative pain, the spared nerve injury (SNI) model of traumatic nerve injury, and the ZDF rat and db/db mouse models of PDN. We administered pioglitazone by one-time intrathecal or intraperitoneal injection or by adding it to chow for 6 weeks, followed by measurement of hypersensitivity to non-noxious mechanical, noxious mechanical, heat, and/or cold stimuli. In all mouse models, injection of pioglitazone decreased pain-like behaviors with greater potency and/or efficacy in females as compared to males heat and mechanical hypersensitivity in the MG model (0.1-10 mg/kg); mechanical hypersensitivity in the PIM model (10 μg); mechanical and cold hypersensitivity in the SNI model (100 mg/kg); and heat hypersensitivity in the db/db model (100 mg/kg). Furthermore, co-administration of low doses of morphine (1 mg/kg) and pioglitazone (10 mg/kg) decreased SNI-induced mechanical and cold hypersensitivity in female but not male mice. In the ZDF rat, pioglitazone (100 mg/kg) decreased heat and mechanical hypersensitivity with no sex difference. In the db/db model, pioglitazone had no effect when given into chow for 6 weeks at 0.3, 3 or 30 mg/kg doses. We conclude that females exhibit greater anti-hyperalgesic responses to pioglitazone in mouse models of chemical-induced nociception, postsurgical pain, neuropathic pain, and PDN. These findings set the stage for clinical trials to determine whether pioglitazone has analgesic properties across a broad spectrum of chronic pain conditions, particularly in women.Osteoarthritis (OA) is a chronic joint disease in which cartilage degeneration leads to chronic pain. The endocannabinoid system has attracted attention as an emerging drug target for OA. However, the therapeutic potential of cannabinoids is limited by psychoactive side-effects related to CB1 activation and tolerance development for analgesic effects. β-Caryophyllene (BCP) is a low-efficacy natural agonist of CB2 and a common constituent of human diet with well-established anti-inflammatory properties. The results presented herein show the anti-nociceptive and chondroprotective potential of BCP in an animal model of OA induced by intra-articular injection of monoiodoacetate (MIA). Behavioural assessment included pressure application measurement and kinetic weight bearing tests. Histological assessment of cartilage degeneration was quantified using OARSI scoring. Experiments established the dose-response effects of BCP and pharmacological mechanisms of the antinociceptive action dependent on CB2 and opioid receptors. Chronic BCP treatment was able to hamper cartilage degeneration without producing tolerance for the analgesic effects. The data presented herein show that BCP is able to produce both acute and prolonged antinociceptive and chondroprotective effects. Together with the safety profile and legal status of BCP, these results indicate a novel and promising disease-modifying strategy for treating OA.An accurate estimate of the number of infected individuals in any disease is crucial. Current estimates are mainly based on the fraction of positive samples or the total number of positive samples. However, both methods are biased and sensitive to the sampling depth. We here propose an alternative method to use the attributes of each sample to estimate the change in the total number of positive patients in the total population. We present a Bayesian estimator assuming a combination of condition and time-dependent probability of being positive, and mixed implicit-explicit solution for the probability of a person with conditions i at time t of being positive. We use this estimate to predict the total probability of being positive at a given day t. We show that these estimate results are smooth and not sensitive to the properties of the samples. Moreover, these results are a better predictor of future mortality.Brief psychotic episodes represent an intriguing paradox in clinical psychiatry because they elude the standard knowledge that applies to the persisting psychotic disorders such as schizophrenia. This Review describes key diagnostic considerations such as conceptual foundations, current psychiatric classification versus research-based operationalisations, epidemiology, and sociocultural variations; prognostic aspects including the risk of psychosis recurrence, types of psychotic recurrences, other clinical outcomes, prognostic factors; and therapeutic issues such as treatment guidelines and unmet need of care. The advances and challenges associated with the scientific evidence are used to set a research agenda in this area. We conclude that brief psychotic episodes can be reconceptualised within a clinical staging model to promote innovative translational research and improve our understanding and treatment of psychotic disorders.