Rejected

The present article is devoted to the action of endocannabinoids via stimulation of their corresponding receptors. It is well established the existence of three type of endocannabinoids (ECS) such as anandamide (AA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PE) providing their effects by activation of CB1 and CB2 ECS receptors. AA is a partial agonist for both receptors, having more affinity for CB1 receptors, while 2-AG reveals an equal agonistic properties to both of them in contrast to PE, which may bind to a unidental "CB2-like" receptors. CB1 receptors are distributed in the central and peripheral nervous system being identified in the greater amounts in the brain cortex, basal ganglia, spinal cord, cerebellum, hippocampus and olfactory areas, owing for the modulatory action of ECS on cognitive function, memory, behaviour, emotion and locomotor activity. Their location in the periaqueductal grey matter and dorsal spinal cord may explain their involvement in pain sensation and modulation. Colocallization of the CB1 receptors with the oroxinergic projection system in the lateral hypothalamus is responsible for their implication in feeding behaviour. CB2 receptors were found in the cells of immune system (spleen, macrophages). It should be noted that ECS may also play a role in the regulation of fertility and pre-and postnatal development. The stimulation of ECS receptors is associated with the activation of MAPK, PI/PKB and MEK/ERK signalling pathways with increased activity of different transcription factors. CB1 receptors are involved in neuronal exitability by decreasing synaptic input, implying retrograde transmission and presynaptic inhibition resulting in reduction of neurotransmitter release. In the article it is also described an ionic mechanisms of release of ECS and the steps of their synthesis as well as participation of a transporter in ECS uptaken process in neurons and astrocytes. Aside from this it is proposed the mechanisms of analgesic action of ECS especially concerning reduction in neuropathic pain in comparison to opioids and possible involvement of α2-adrenoceptors in antinociceptive activity of ECS. Some analgesic properties of ECS is due to their inhibitory action on cyclooxygenase-2 (COX-2). Recent evidences showed that regarding antinociceptive action of ECS along with CB1 receptors most significant receptors are PPAR-alpha and TRPV receptors. There are controversial data concerning the influence of ECS on cognitive function. Knockout mices with the absence of CB1 receptors have showed improved memory and long-term potentiation proofing the significant role of ECS in the disorders of "old memories". Some data suggests that genetic or pharmacological inhibition of COX-2 activity may reduce disorders in hippocampal long-term synaptic plasticity and fear memory, as well as supports improving effects of tetrahydrocannabinoids (THC) on neurodegenerative processes such as Alzheimer's disease, because THC facilitates to marked expression of an important endopeptidase neprilysin for degradation of AB proteins. A number of evidence indicates the possible involvement of ECS in schizophrenia and major depressive disorders. Assumingly such beneficial effect of ECS is associated with M1/M2 microglial polarization process. In conclusion it is suggested that ECS as natural ligand for their corresponding receptors provide wide spectrum of pharmacological effects may become an interesting targets for future therapeutic intervention.

Osteoarthritis (OA) is a degenerative joint disease characterized by inflammatory degradation of articular cartilage and subchondral bone. Wogonin, a compound extracted from the plant (colloquially known as skullcap), has previously been shown to have direct anti-inflammatory and antioxidative properties. We examined the pain-reducing, anti-inflammatory, and chondroprotective effects of wogonin when applied as a topical cream. We validated the efficacy of delivering wogonin transdermally in a cream using pig ear skin in a Franz diffusion system. Using a surgical mouse model, we examined the severity and progression of OA with and without the topical application of wogonin. Using a running wheel to track activity, we found that mice with wogonin treatment were statistically more active than mice receiving vehicle treatment. OA progression was analyzed using modified Mankin and OARSI scoring and direct quantification of cyst-like lesions at the chondro-osseus junction; in each instance we observed a statistically significant attenuation of OA severity among mice treated with wogonin compared to the vehicle treatment. Immunohistochemistry revealed a significant decrease in protein expression of transforming growth factor β1 (TGF-β1), high temperature receptor A1 (HTRA1), matrix metalloprotease 13 (MMP-13) and NF-κB in wogonin-treated mice, further bolstering the cartilage morphology assessments in the form of a decrease in inflammatory and OA biomarkers.

To study the efficacy of pregabalin for relapse prevention and reduction of drinking in patients with alcohol dependence.

Gut microbiota dysbiosis has adverse health effects on human body. Multi-drug-resistant tuberculosis (MDR-TB) treatment uses a variety of antibiotics typically for more than 20 months, which may induce gut microbiota dysbiosis. The aim of this study is to investigate the long-term effects of MDR-TB treatment on human gut microbiota and its related health consequences. A total of 76 participants were recruited at a hospital in Linyi, China. The study included one active MDR-TB treatment group, one recovered group from MDR-TB and two treatment-naive tuberculosis groups as control. The two treatment-naïve tuberculosis groups were constructed to match the sex and the age of the active MDR-TB treatment and the recovered group, respectively. The fecal and blood samples were collected and analyzed for gut microbiota and metabolic parameters. An altered gut microbiota community and a loss of richness were observed during the MDR-TB treatment. Strikingly, 3-8 years after recovery and discontinuing the treatment, the gut microbiota still exhibited an altered taxonomic composition ( = 0.001) and a 16% decrease in richness ( = 0.018) compared to the gut microbiota before the treatment. The abundance of fifty-eight bacterial genera was significantly changed in the MDR-TB recovered group versus the untreated control group. Although there were persistent and pervasive gut microbiota alterations, no gastrointestinal symptom such as abdominal pain, diarrhea, nausea, flatulence, and constipation was observed in the recovered group. However, chronic disorders may be indicated by the elevated level of low-density lipoprotein cholesterol (LDLC) ( = 0.034) and total cholesterol (TC) ( = 0.017). These adverse lipid changes were associated with the altered gut bacterial taxa, including phylum Firmicutes and Verrucomicrobia and genera , , , , , , , , , and . Collectively, MDR-TB treatment induced a lasting gut microbiota dysbiosis, which was associated with unfavorable changes in lipid profile.

Chronic spontaneous urticaria (CSU) is characterized by the repeated occurrence by persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H -antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add-on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium.

Internal jugular vein (IJV) thrombosis is a rare vascular event. It is most commonly due to prolonged central venous catheterization, infection, ovarian hyperstimulation syndrome, intravenous drug abuse, malignancy or primary. We have present here a case of a 82- year- old male with chronic kidney disease who presented with left neck swelling and pain who was found to have a thrombus in the left internal internal jugular vein. He was successfully treated with conservative treatment without any complications.

We report here a case of inflammatory bursitis in a patient with crohn's disease after switching to biosimilar infliximab.

The symptoms of irritable bowel syndrome (IBS) lead to considerable impairment of health-related quality of life and high health care costs. Available therapies are not efficient in treating the symptoms of IBS. Studies have shown the beneficial effects of Saccharomyces cerevisiae CNCM I-3856. Therefore, this study was done to evaluate the efficacy and safety of S. cerevisiae CNCM I-3856 in the treatment of IBS.

Pancreaticopleural fistula is a rare complication of both acute and chronic pancreatitis. Here, we present a case of a pancreaticopleural fistula treated with Video-Assisted Retroperitoneal Debridement (VARD).

Immune cells secrete small protein molecules that aim for cell-cell communications. These small molecules are called cytokines. Targeting cancer cells with administration of bispecific antibodies and natural extracts results in elevated circulating levels of inflammatory cytokines, including interferon-γ and interleukin (IL)-6, which lead to cell toxicity. Sustained release of cytokines due to immunotherapy or hormonal issues causes various diseases. Novel T cell-engaging therapies and monoclonal antibodies cause cytokine release syndrome. Efforts are being carried out to maximize the chance for therapeutic benefit from immunotherapy while minimizing the risk for life-threatening complications of sustained cytokine release. Neurodegeneration and cardiac diseases are the prominent diseases caused by inflammatory cytokines. The phenomenon is called cytokine storm. Cytokines can act antagonistically or synergistically. Constitutive expression of proinflammatory cytokines such as IL-3 and IL-6 causes organ damage and unbearable pain. In this review, we will discuss the regulators of cytokine release, its types, its implications on human health, and treatment.