Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota–gut–brain axis, including in Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients’ gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.

Hydrogen sulfide (H₂S), a gas traditionally considered toxic, is now recognized as a vital endogenous signaling molecule with a complex physiology. This comprehensive study encompasses a systematic literature review that explores the intricate mechanisms underlying H₂S-induced vasodilation. The vasodilatory effects of H₂S are primarily mediated by activating ATP-sensitive potassium (K_ATP) channels, leading to membrane hyperpolarization and subsequent relaxation of vascular smooth muscle cells (VSMCs). Additionally, H₂S inhibits L-type calcium channels, reducing calcium influx and diminishing VSMC contraction. Beyond ion channel modulation, H₂S profoundly impacts cyclic nucleotide signaling pathways. It stimulates soluble guanylyl cyclase (sGC), increasing the production of cyclic guanosine monophosphate (cGMP). Elevated cGMP levels activate protein kinase G (PKG), which phosphorylates downstream targets like vasodilator-stimulated phosphoprotein (VASP) and promotes smooth muscle relaxation. The synergy between H₂S and nitric oxide (NO) signaling further amplifies vasodilation. H₂S enhances NO bioavailability by inhibiting its degradation and stimulating endothelial nitric oxide synthase (eNOS) activity, increasing cGMP levels and potent vasodilatory responses. Protein sulfhydration, a post-translational modification, plays a crucial role in cell signaling. H₂S S-sulfurates oxidized cysteine residues, while polysulfides (H₂Sn) are responsible for S-sulfurating reduced cysteine residues. Sulfhydration of key proteins like K_ATP channels and sGC enhances their activity, contributing to the overall vasodilatory effect. Furthermore, H₂S interaction with endothelium-derived hyperpolarizing factor (EDHF) pathways adds another layer to its vasodilatory mechanism. By enhancing EDHF activity, H₂S facilitates the hyperpolarization and relaxation of VSMCs through gap junctions between endothelial cells and VSMCs. Recent findings suggest that H₂S can also modulate transient receptor potential (TRP) channels, particularly TRPV4 channels, in endothelial cells. Activating these channels by H₂S promotes calcium entry, stimulating the production of vasodilatory agents like NO and prostacyclin, thereby regulating vascular tone. The comprehensive understanding of H₂S-induced vasodilation mechanisms highlights its therapeutic potential. The multifaceted approach of H₂S in modulating vascular tone presents a promising strategy for developing novel treatments for hypertension, ischemic conditions, and other vascular disorders. The interaction of H₂S with ion channels, cyclic nucleotide signaling, NO pathways, ROS (Reactive Oxygen Species) scavenging, protein sulfhydration, and EDHF underscores its complexity and therapeutic relevance. In conclusion, the intricate signaling paradigms of H₂S-induced vasodilation offer valuable insights into its physiological role and therapeutic potential, promising innovative approaches for managing various vascular diseases through the modulation of vascular tone.

Background: Stroke is a significant public health problem and a leading cause of death and long-term disability worldwide. Several treatments for ischemic stroke have been developed, but these treatments have limited effectiveness. One potential treatment for this condition is Actovegin^®/AODEJIN, a calf blood deproteinized hemodialysate/ultrafiltrate that has been shown to have pleiotropic/multifactorial and possibly multimodal effects. The actual actions of this medicine are thought to be mediated by its ability to reduce oxidative stress, inflammation, and apoptosis and to enhance neuronal survival and plasticity. Methods: To obtain the most up-to-date information on the effects of Actovegin^®/AODEJIN in ischemic stroke, we systematically reviewed the literature published in the last two years. This review builds upon our previous systematic literature review published in 2020, which used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to search for and select related articles over almost two decades, between 1 January 2001 and 31 December 2019. Additionally, we compared the results of our PRISMA search (human intelligence-based) with those obtained from an interrogation of a GPT-based chatbot (ChatGPT) in order to ensure comprehensive coverage of potentially relevant studies. Results: Our updated review found limited new evidence on the use of Actovegin^®/AODEJIN in ischemic stroke, although the number of articles on this subject consistently increased compared to that from our initial systematic literature review. Specifically, we found five articles up to 2020 and eight more until December 2022. While these studies suggest that Actovegin^®/AODEJIN may have neuroprotective effects in ischemic stroke, further clinical trials are needed to confirm these findings. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Discussion: Our funnel analysis showed no evidence of publication bias, suggesting that the limited number of studies identified was not due to publication bias but rather due to a lack of research in this area. However, there are limitations when using ChatGPT, particularly in distinguishing between truth and falsehood and determining the appropriateness of interpolation. Nevertheless, AI can provide valuable support in conducting PRISMA-type systematic literature reviews, including meta-analyses. Conclusions: The limited number of studies identified in our review highlights the need for additional research in this area, especially as no available therapeutic agents are capable of curing central nervous system lesions. Any contribution, including that of Actovegin (with consideration of a positive balance between benefits and risks), is worthy of further study and periodic reappraisal. The evolving advancements in AI may play a role in the near future.

Background/Objectives: Given the significant economic and social burden of osteoporosis, there is growing interest in developing an efficient alternative to the traditional dual-energy X-ray absorptiometry (DXA). Radiofrequency Echographic Multi Spectrometry (REMS) is an innovative, non-ionizing imaging technique that recently emerged as a viable tool to diagnose osteoporosis and estimate the fragility fracture risk. Nevertheless, its clinical use is still limited due to its novelty and continuing uncertainty of long-term performance. Methods: In order to evaluate the accuracy of the REMS, a systematic review of the English-language literature was conducted. Three databases were searched for relevant publications from 1 January 2015 until 1 December 2024 using the keyword combinations “(radiofrequency echographic multi spectrometry OR REMS) AND (dual-energy X-ray absorptiometry OR DXA)”. The initial search yielded 602 candidate articles. After screening the titles and abstracts following the eligibility criteria, 17 publications remained for full-text evaluation. Results: The reviewed studies demonstrated strong diagnostic agreement between REMS and DXA. Additionally, REMS showed enhanced diagnostic capabilities in cases where lumbar bone mineral density measurements by DXA were impaired by artifacts such as vertebral fractures, deformities, osteoarthritis, or vascular calcifications. REMS exhibited excellent intra-operator repeatability and precision, comparable to or exceeding the reported performance of DXA. The fragility score (FS), a parameter reflecting bone quality and structural integrity, effectively discriminated between fractured and non-fractured patients. Moreover, REMS proved to be a radiation-free option for bone health monitoring in radiation-sensitive populations or patients requiring frequent imaging to assess fracture risk. Conclusions: This current study underscores the robustness of REMS as a reliable method for diagnosing and monitoring osteoporosis and evaluating bone fragility via the FS. It also identifies critical knowledge gaps and emphasizes the need for further prospective studies to validate and expand the clinical applications of REMS across diverse patient populations.

One of the most complex and challenging developments at the beginning of the third millennium is the alarming increase in demographic aging, mainly—but not exclusively—affecting developed countries. This reality results in one of the harsh medical, social, and economic consequences: the continuously increasing number of people with dementia, including Alzheimer’s disease (AD), which accounts for up to 80% of all such types of pathology. Its large and progressive disabling potential, which eventually leads to death, therefore represents an important public health matter, especially because there is no known cure for this disease. Consequently, periodic reappraisals of different therapeutic possibilities are necessary. For this purpose, we conducted this systematic literature review investigating nonpharmacological interventions for AD, including their currently known cellular and molecular action bases. This endeavor was based on the PRISMA method, by which we selected 116 eligible articles published during the last year. Because of the unfortunate lack of effective treatments for AD, it is necessary to enhance efforts toward identifying and improving various therapeutic and rehabilitative approaches, as well as related prophylactic measures.

For many years, inflammatory rheumatic diseases (IRDs) represented a source of disappointment in medical care caused by the mediocre efficacy of the available treatments. Some of these diseases, like Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS), caused fear in the general population, especially due to associated joint deformities and subsequent disabilities. However, in the last 20 years, a new successful class of antirheumatic drugs has become available: biologic Disease-Modifying Antirheumatic Drugs (bDMARDs). Due to this innovative treatment, the days are over when joint and spine deformities defined the condition of a person with RA or AS. Nonetheless, expectations are higher today, and other clinical problems, (not entirely solved by bDMARDs), seem to drive the drug selection during the span of rheumatic diseases. Most of these issues are covered by the term “unmet needs.” One of the most intriguing of such needs is the residual pain (RP) in patients that are otherwise in the biological remission of the disease. Present in a significant proportion of the patients that enter remission status, RP is poorly understood and managed. In recent years, new data has become available in this area and new conceptual clarifications have occurred. In this review, we explain the various nature of RP and the necessity of treatment diversification in such situations. All in all, we believe this condition is far more complex than simple pain and includes other clinical aspects, too (like fatigue or mood changes) so the terms Post-Remission Syndrome (PRS), and PRS pain might be more appropriate.