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Physiological Research Jul 2024Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However,...
Three decades ago, the first endocannabinoid, anandamide (AEA), was identified, and its analgesic effect was recognized in humans and preclinical models. However, clinical trial failures pointed out the complexity of the AEA-induced analgesia. The first synapses in the superficial laminae of the spinal cord dorsal horn represent an important modulatory site in nociceptive transmission and subsequent pain perception. The glutamatergic synaptic transmission at these synapses is strongly modulated by two primary AEA-activated receptors, cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), both highly expressed on the presynaptic side formed by the endings of primary nociceptive neurons. Activation of these receptors can have predominantly inhibitory (CB1) and excitatory (TRPV1) effects that are further modulated under pathological conditions. In addition, dual AEA-mediated signaling and action may occur in primary sensory neurons and dorsal horn synapses. AEA application causes balanced inhibition and excitation of primary afferent synaptic input on superficial dorsal horn neurons in normal conditions, whereas peripheral inflammation promotes AEA-mediated inhibition. This review focuses mainly on the modulation of synaptic transmission at the spinal cord level and signaling in primary nociceptive neurons by AEA via CB1 and TRPV1 receptors. Furthermore, the spinal analgesic effect in preclinical studies and clinical aspects of AEA-mediated analgesia are considered.
PubMed: 38957948
DOI: No ID Found -
Applied Psychology. Health and... Jul 2024Encouraging engagement in rewarding or pleasant activities is one of the most important treatment goals for depression. Mental imagery exercises have been shown to...
Encouraging engagement in rewarding or pleasant activities is one of the most important treatment goals for depression. Mental imagery exercises have been shown to increase the motivation for planned behaviour in the lab but it is unclear whether this is also the case in daily life. Therefore, we aimed to investigate the effect of mental imagery exercises on motivation and behaviour in daily life. Participants with depressive symptoms (N = 59) were randomly assigned to a group receiving mental imagery (MI) exercises or a control group receiving relaxation (RE) exercises via study phones. We employed an experience sampling design with 10 assessments per day for 10 days (three days baseline, four days with two exercises per day and three days post-intervention). Data was analysed using t-tests and multilevel linear regression analyses. As predicted, MI exercises enhanced motivation and reward anticipation during the intervention phase compared to RE. However, MI did not enhance active behaviour or strengthen the temporal association from reward anticipation (t-1) to active behaviour (t). Mental imagery exercises can act as a motivational amplifier but its effects on behaviour and real-life reward processes remain to be elucidated.
PubMed: 38957927
DOI: 10.1111/aphw.12572 -
Cureus Jul 2024Chronic pain is a complex condition that often poses diagnostic and management challenges due to its multifactorial etiology. This case report describes a 49-year-old...
A Novel Ultrasound-Guided Bilateral Vagal Nerve Hydrodissection With 5% Dextrose Without Local Anesthetic for Recalcitrant Chronic Multisite Pain and Autonomic Dysfunction.
Chronic pain is a complex condition that often poses diagnostic and management challenges due to its multifactorial etiology. This case report describes a 49-year-old pastor who presented with a three-year history of chronic pain affecting multiple sites, including the neck, bilateral shoulders, thoracic region, lower back, and bilateral knees. Additionally, he experienced shortness of breath on mild exertion, which adversely affected his ability to converse and speak publicly. The patient had a rapid resting heart rate of 100-120 beats per minute, occasional palpitations, and a 24-hour electrocardiogram that confirmed 15% premature ventricular complexes with bigeminy and trigeminy. He complained of limited appetite with early satiety, intermittent nausea, and regurgitation. Despite consultations with multiple specialists, no underlying causes were identified in the cardiac, respiratory, gastrointestinal, or psychological domains. Ultrasound-guided bilateral vagus nerve hydrodissection using 5% dextrose without local anesthetics was administered three times at monthly intervals, resulting in remarkable pain relief within three months and the effects persisted at the nine-month follow-up. Tachycardia was no longer perceived, resting heart rate slowed to 70-80 beats per minute, shortness of breath improved, and public speaking ability was restored. The patient's early satiety, nausea, and reflux complaints were resolved. This case report highlights the potential effectiveness of this novel intervention for chronic pain. Further research is warranted to validate these findings and explore the mechanism of action.
PubMed: 38957517
DOI: 10.7759/cureus.63609 -
Frontiers in Immunology 2024Probiotic consumption strongly influences local intestinal immunity and systemic immune status. strain SANK70258 (HC) is a spore-forming lactic acid bacterium that has... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
strain SANK70258 suppresses symptoms of upper respiratory tract infection via immune modulation: a randomized, double-blind, placebo-controlled, parallel-group, comparative study.
Probiotic consumption strongly influences local intestinal immunity and systemic immune status. strain SANK70258 (HC) is a spore-forming lactic acid bacterium that has immunostimulatory properties on peripheral tissues. However, few reports have examined the detailed effectiveness of HC on human immune function and its mechanism of action. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to comprehensively evaluate the effects of HC on immunostimulatory capacity, upper respiratory tract infection (URTI) symptoms, and changes in intestinal organic-acid composition. Results of a questionnaire survey of URTI symptoms showed that runny nose, nasal congestion, sneezing, and sore throat scores as well as the cumulative number of days of these symptoms were significantly lower in the HC group than in the placebo group during the study period. Furthermore, the salivary secretory immunoglobulin A (sIgA) concentration was significantly higher, and the natural killer (NK) cell activity tended to be higher in the HC group than in the placebo group. In addition, we performed an exposure culture assay of inactivated influenza virus on peripheral blood mononuclear cells (PBMCs) isolated from the blood of participants in the HC and placebo groups. Gene-expression analysis in PBMCs after culture completion showed that IFNα and TLR7 expression levels were significantly higher in the HC group than in the placebo group. In addition, the expression levels of CD304 tended to be higher in the HC group than in the placebo group. On the other hand, the HC group showed a significantly higher increase in the intestinal butyrate concentration than the placebo group. HC intake also significantly suppressed levels of IL-6 and TNFα produced by PBMCs after exposure to inactivated influenza virus. Collectively, these results suggest that HC activated plasmacytoid dendritic cells expressing TLR7 and CD304 and strongly induced IFNα production, subsequently activating NK cells and increasing sIgA levels, and induced anti-inflammatory effects via increased intestinal butyrate levels. These changes may contribute to the acquisition of host resistance to viral infection and URTI prevention.
Topics: Humans; Respiratory Tract Infections; Double-Blind Method; Male; Adult; Probiotics; Female; Young Adult; Leukocytes, Mononuclear; Killer Cells, Natural; Gastrointestinal Microbiome; Immunoglobulin A, Secretory; Toll-Like Receptor 7; Immunomodulation
PubMed: 38957464
DOI: 10.3389/fimmu.2024.1389920 -
Addiction Neuroscience Jun 2024Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (μORs). The μOR is encoded by the gene and is expressed in multiple...
Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (μORs). The μOR is encoded by the gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies have revealed that multiple subpopulations of NAc neurons express mRNA, making it unclear which populations mediate diverse behaviors resulting from μOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels of of any NAc cell type. Here, we show that this population is selectively marked by expression of , a gene encoding a carbohydrate sulfotransferase. Notably, + neurons exhibited more abundant expression of as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover, mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression of . The abundant expression of in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.
PubMed: 38957401
DOI: 10.1016/j.addicn.2024.100153 -
JBMR Plus Aug 2024Iron is a vital trace element and exerts opposing effects on bone in both iron overload and iron deficiency situations. Remarkably, iron supplementation through... (Review)
Review
Iron is a vital trace element and exerts opposing effects on bone in both iron overload and iron deficiency situations. Remarkably, iron supplementation through intravenous infusion in patients with iron deficiency can also have detrimental effects on bone in special cases. The diverse mechanisms underlying these effects and their manifestations contribute to the complexity of this relationship. Iron overload impacts both bone resorption and formation, accelerating bone resorption while reducing bone formation. These effects primarily result from the direct action of reactive oxygen species (ROS), which influence the proliferation, differentiation, and activity of both osteoclasts and osteoblasts differently. This imbalance favors osteoclasts and inhibits the osteoblasts. Simultaneously, multiple pathways, including bone morphogenic proteins, RANK ligand, and others, contribute to these actions, leading to a reduction in bone mass and an increased susceptibility to fractures. In contrast, iron deficiency induces low bone turnover due to energy and co-factor deficiency, both of which require iron. Anemia increases the risk of fractures in both men and women. This effect occurs at various levels, reducing muscular performance and, on the bone-specific level, decreasing bone mineral density. Crucially, anemia increases the synthesis of the phosphaturic hormone iFGF23, which is subsequently inactivated by cleavage under physiological conditions. Thus, iFGF23 levels and phosphate excretion are not increased. However, in specific cases where anemia has to be managed with intravenous iron treatment, constituents-particularly maltoses-of the iron infusion suppress the cleavage of iFGF23. As a result, patients can experience severe phosphate wasting and, consequently, hypophosphatemic osteomalacia. This condition is often overlooked in clinical practice and is often caused by ferric carboxymaltose. Ending iron infusions or changing the agent, along with phosphate and vitamin D supplementation, can be effective in addressing this issue.
PubMed: 38957399
DOI: 10.1093/jbmrpl/ziae064 -
Frontiers in Pharmacology 2024Emergence of drug resistant strains of species has necessitated the search for novel antimalarials with unique mechanisms of action. Synthesis of hybrid compounds has...
Emergence of drug resistant strains of species has necessitated the search for novel antimalarials with unique mechanisms of action. Synthesis of hybrid compounds has been one approach to tackling this challenge. In this study, the synthesis of artesunate-ellagic acid hybrid compound (EA31) from ellagic acid and artesunate and its evaluation for antimalarial and antioxidant activities using and models were carried out. EA31 was synthesized from artesunate and ellagic acid. The activities of the hybrid compound against Plasmodium falciparum W2 and P. berghei NK65 were evaluated, and its antioxidant activities were also determined. The results revealed that EA31 was more active against W2 (chloroquine resistant) clone and less cytotoxic to buffalo green monkey kidney cell line compared to artesunate. EA31 was also active against NK65 . The results revealed inhibition of β-hematin formation as one of the mechanisms of action of EA31. EA31 also exhibited antioxidant activities. The results revealed that EA31 may exert dual action of killing malaria parasite and mopping the reactive oxygen species that mediate the secondary complications of malaria.
PubMed: 38957387
DOI: 10.3389/fphar.2024.1192659 -
Frontiers in Oncology 2024Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy... (Review)
Review
Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy are examples of mainstream allopathic medicine treatments that effective for intermediate and advanced malignant tumors. The ongoing use of conventional allopathic medicine has resulted in adverse responses and drug resistance, which have hampered its efficacy. As an important component of complementary and alternative medicine, Chinese medicine has been found to have antitumor effects and has played an important role in enhancing the therapeutic sensitivity of mainstream allopathic medicine, reducing the incidence of adverse events and improving immune-related functions. The combined application of adjuvant Chinese medicine and mainstream allopathic medicine has begun to gain acceptance and is gradually used in the field of antitumor therapy. Traditional natural medicines and their active ingredients, as well as Chinese patent medicines, have been proven to have excellent therapeutic efficacy and good safety in the treatment of various malignant tumors. This paper focuses on the mechanism of action and research progress of combining the above drugs with mainstream allopathic medicine to increase therapeutic sensitivity, alleviate drug resistance, reduce adverse reactions, and improve the body's immune function. To encourage the clinical development and use of Chinese herb adjuvant therapy as well as to provide ideas and information for creating safer and more effective anticancer medication combinations, the significant functions of Chinese herb therapies as adjuvant therapies for cancer treatment are described in detail.
PubMed: 38957318
DOI: 10.3389/fonc.2024.1412370 -
Cureus Nov 2023Acute myocardial infarction (AMI), commonly referred to as a heart attack, is a leading global cause of mortality, necessitating immediate recognition and appropriate...
INTRODUCTION
Acute myocardial infarction (AMI), commonly referred to as a heart attack, is a leading global cause of mortality, necessitating immediate recognition and appropriate actions. This study aims to assess AMI awareness and response among the general population in Alahssa, Saudi Arabia.
METHODOLOGY
A descriptive cross-sectional design was employed, with surveys distributed via online platforms. Participants aged 18 years and older, residing in Alahssa, and providing informed consent were included.
RESULTS
Among 406 participants, 74.1% had good knowledge levels. Notably, 216 (53.2%) recognized calling an ambulance as the initial response to AMI symptoms. The Internet (140, 28.9%) and healthcare professionals (113, 23.3%) were primary information sources, with "sudden pain or discomfort in arms or hands" (287, 27.8%) as the most recognized symptom. "Obesity" and "heart disease" (304, 12.3%) were the most common risk factors. Demographic variations in knowledge were observed.
CONCLUSION
This study highlights the need to enhance public awareness of AMI, particularly among specific demographic groups. Targeted educational campaigns can improve knowledge, promote appropriate actions, and ultimately enhance outcomes during AMI events in Alahssa, Saudi Arabia.
PubMed: 38957197
DOI: 10.7759/cureus.49300 -
Cureus Nov 2023Subfertility, a prevalent and emotionally taxing condition affecting couples worldwide, has garnered increasing attention in reproductive health. While its etiology... (Review)
Review
Subfertility, a prevalent and emotionally taxing condition affecting couples worldwide, has garnered increasing attention in reproductive health. While its etiology remains multifaceted, emerging research has explored the role of serum homocysteine levels and nutrient deficiencies in influencing subfertility. This comprehensive review synthesizes current knowledge, beginning with an introduction to subfertility and the significance of investigating serum homocysteine levels. It proceeds to elucidate the role of nutrient deficiencies, particularly folate and vitamin B12, in homocysteine metabolism and examines existing research linking homocysteine to subfertility. The review explores potential mechanisms underlying this relationship, addressing the variability in study findings and their contributing factors. Implications for clinical practice, including assessing serum homocysteine levels, nutritional interventions, and personalized medicine, are discussed. Moreover, the review underscores the importance of ongoing research. It offers a call to action for advancing our understanding of subfertility and improving the lives of individuals and couples navigating reproduction challenges.
PubMed: 38957192
DOI: 10.7759/cureus.49296