Rejected

Migraine and epilepsy are fundamentally distinct disorders that can frequently coexist in the same patient. These two conditions have significant differences in diagnosis and therapy but share some widely-used preventive treatments. Antiseizure medications (ASMs) are the mainstay of therapy for epilepsy and about thirty different ASMs are available to date. ASMs are widely prescribed for other neurological and non-neurological conditions, including migraine. However, only topiramate and valproic acid/valproate currently have an indication for migraine prophylaxis that is supported by high-quality evidence. Although without specific approved indications, and with a low level of evidence or recommendation, several other ASMs are used for migraine prophylaxis. Understanding ASM antimigraine mechanisms, including their ability to affect the pro-migraine calcitonin gene-related peptide (CGRP) signaling pathway and other pathways, may be instrumental in identifying the specific targets of their antimigraine efficacy and may increase awareness of the neurobiological differences between epilepsy and migraine. Several new ASMs are under clinical testing or have been approved for epilepsy in recent years, providing novel potential drugs for migraine prevention to enrich the treatment armamentarium along with drugs that inhibit the CGRP pathway.

Lavender is a valuable medicinal plant belonging to the family. Currently 39 species are known, but only is a pharmacopoeial raw material. Lavender has a long history of medicinal use and mainly exhibits antioxidant, anti-inflammatory, sedative, antidepressant, spasmolytic, anticholinesterases, antifungal and antibacterial properties. Used internally, it relieves symptoms of mental stress and insomnia and supports digestion. Topical use of lavender in aromatherapy, neuralgia and antiseptics is also known. The constant interest in lavender, and in particular in , in the field of medicine and pharmacy is evidenced by the growing number of publications. In view of so many studies, it seems important to review traditional and modern extraction techniques that determine the chemical composition responsible for the antioxidant and anti-inflammatory effects of various extracts from the species of the genus.

Chemotherapy-induced neuropathy represents the main dose-limiting toxicity of several anticancer drugs, such as oxaliplatin, leading to chronic pain and an impairment of the quality of life. Echinacea purpurea n-hexane extract (EP -R ; rich in alkamides) and butanolic extract (EP -R ; rich in polyphenols) have been characterized and tested in an in vivo model of oxaliplatin-induced neuropathic pain, addressing the endocannabinoid system with alkamides and counteracting the redox imbalance with polyphenols. Thermal hypersensitivity was evaluated by the Cold Plate test. EP -R showed a dose-dependent anti-hyperalgesic profile. The extract was more effective than its main constituent, dodeca-2 E,4 E,8Z,10 E/Z-tetraenoic acid isobutylamide (18 mg kg , twofold to equimolar EP -R 30 mg kg ), suggesting a synergy with other extract constituents. Administration of cannabinoid type 2 (CB2) receptor-selective antagonist completely blocked the anti-allodynic effect of EP -R , differently from the antagonism of CB1 receptors. EP -R (30 mg kg ) exhibited anti-neuropathic properties too. The effect was mainly exerted by chicoric acid, which administered alone (123 μg kg , equimolar to EP -R 30 mg kg ) completely reverted oxaliplatin-induced allodynia. A synergy between different polyphenols in the extract had not been highlighted. Echinacea extracts have therapeutic potential in the treatment of neuropathic pain, through both alkamides CB2-selective activity and polyphenols protective properties.

Ponciri Fructus is a crude drug obtained from the dried immature fruits of (L). Raf. (Syn. L.). This study aims to compile and analyze the ethnomedicinal uses, bioactive constituents, and pharmacological activities of Ponciri Fructus. Various online bibliographic databases namely, SciFinder, PubMed, Google Scholar, and Web of Science were used for collecting information on traditional uses, biological activities, and bioactive constituents. Concerning ethnomedicinal uses, Ponciri Fructus is extensively used in traditional Korean, Chinese, and Kampo medicines to mitigate allergic reactions, inflammation, edema, digestive complications, respiratory problems, spleen-related problems, liver complications, neuronal pain, hyperlipidemia, rheumatoid arthritis, cardiovascular problems, hernia, sinusitis, and insomnia. Several studies have shown that Ponciri Fructus is a major source of diverse classes of bioactive compounds namely flavonoids, terpenoids, coumarins, phytosterols, and alkaloids. Several in vivo and in vitro pharmacological activity evaluations such as antidiabetic, anti-obesity, anti-inflammatory, antiallergic, antimelanogenic, gastroprotective, anticancer, and neuroprotective effects have been conducted from Ponciri Fructus. However, scientific investigations focusing on bioassay-guided isolation and identification of specific bioactive constituents are limited. Therefore, an in-depth scientific investigation of Ponciri Fructus focusing on bioassay-guided isolation, mechanism based pharmacological studies, pharmacokinetic studies, and evaluation of possible toxicities is necessary in the future.

Recent community-based studies have demonstrated that experiencing multiple concurrent functional gastrointestinal disorders (FGIDs) is associated with increased somatization, worse quality of life (QoL), and greater health care utilization. However, the presence of multiple overlapping FGIDs is unstudied specifically in chronic constipation and functional defecation disorders (FDD). We investigated the prevalence and impact of additional nonconstipation FGIDs on constipation severity, anorectal physiology, anxiety and depression, and QoL, in patients with chronic constipation and FDD.

The multitarget-directed ligands demonstrating affinity to histamine H receptor and additional cholinesterase inhibitory potency represent a promising strategy for research into the effective treatment of Alzheimer's disease. In this study, a novel series of benzophenone derivatives was designed and synthesized. Among these derivatives, we identified compound with a high affinity for HR ( = 8 nM) and significant inhibitory activity toward BuChE (IC = 172 nM and 1.16 µM for BuChE and BuChE, respectively). Further in vitro studies revealed that compound (4-fluorophenyl) (4-((5-(piperidin-1-yl)pentyl)oxy)phenyl)methanone) displays moderate metabolic stability in mouse liver microsomes, good permeability with a permeability coefficient value (P) of 6.3 × 10 cm/s, and its safety was confirmed in terms of hepatotoxicity in the HepG2 cell line. Therefore, we investigated the in vivo activity of compound in the Passive Avoidance Test and the Formalin Test. While compound did not show a statistically significant influence on memory and learning, it showed analgesic properties in both acute (ED = 20.9 mg/kg) and inflammatory (ED = 17.5 mg/kg) pain.

Published literature on central nervous system (CNS) coccidioidomycosis in children is limited. Here we describe a large case series of pediatric CNS coccidioidomycosis from a tertiary care center in an endemic region.

Chronic non-specific low back pain (CNLBP) is the most common musculoskeletal problem. The purpose of this study was to investigate the effects of advanced physiotherapeutic exercise programs on imaging findings and inflammatory biomarkers in soccer players with CNLBP. In total, 60 CNLBP participants were divided into virtual reality exercise (VRE; = 20), isokinetic exercise (IKE; = 20), and conventional exercise ( = 20) groups. Pain intensity, imaging findings (muscle cross-sectional area (CSA) and muscle thickness), and changes in inflammatory biomarkers (CRP, TNF-α, IL-2, IL-4, and IL-6) were measured at baseline and after four weeks. After four weeks of intervention, there was a significant improvement ( = 0.001) in pain intensity for the VRE vs. IKE (0.7; CI 95% 0.38 to 1.07) and VRE vs. conventional (3.0 CI 95% 2.68 to 3.31) groups. The IKE group showed a greater number of significant changes in muscle CSA and muscle thickness than the other two groups ( < 0.001). Moreover, the VRE group showed significant improvement in inflammatory biomarker measures compared with the other two groups ( < 0.001). In CNLBP, virtual and isokinetic exercises had equal effects on reducing pain intensity. Isokinetic exercise is beneficial in increasing the muscle CSA and thickness, and virtual exercises are helpful for attenuating the inflammation process in soccer players with CNLBP.

Retrospective cohort study.

Spinal Cord Injury (SCI) is a common neurological disorder with devastating psychical and psychosocial sequelae. The majority of patients after SCI suffer from permanent disability caused by motor dysfunction, impaired sensation, neuropathic pain, spasticity as well as urinary complications, and a small number of patients experience a complete recovery. Current standard treatment modalities of the SCI aim to prevent secondary injury and provide limited recovery of lost neurological functions. Stem Cell Therapy (SCT) represents an emerging treatment approach using the differentiation, paracrine, and self-renewal capabilities of stem cells to regenerate the injured spinal cord. To date, multipotent stem cells including mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs) represent the most investigated types of stem cells for the treatment of SCI in preclinical and clinical studies. The microenvironment of SCI has a significant impact on the survival, proliferation, and differentiation of transplanted stem cells. Therefore, a deep understanding of the pathophysiology of SCI and molecular mechanisms through which stem cells act may help improve the treatment efficacy of SCT and find new therapeutic approaches such as stem-cell-derived exosomes, gene-modified stem cells, scaffolds, and nanomaterials. In this literature review, the pathogenesis of SCI and molecular mechanisms of action of multipotent stem cells including MSCs, NSCs, and HSCs are comprehensively described. Moreover, the clinical efficacy of multipotent stem cells in SCI treatment, an optimal protocol of stem cell administration, and recent therapeutic approaches based on or combined with SCT are also discussed.