Search Results (611)

In recent years, the bidirectional regulatory mechanism of the bone-brain axis has become a hotspot for interdisciplinary research. In this paper, we systematically review the anatomical and functional links between bone and the central nervous system, focusing on the regulation of brain function by bone-derived signals and their clinical translational potential. At the anatomical level, the blood–brain barrier permeability mechanism and the unique structure of the periventricular organs establish the anatomical basis for bone-brain information transmission. Innovative discoveries indicate that the bone cell network (bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone marrow monocytes) directly regulates neuroplasticity and the inflammatory microenvironment through the secretion of factors such as osteocalcin, lipid transporter protein 2, nuclear factor κB receptor-activating factor ligand, and fibroblast growth factor 23, as well as exosome-mediated remote signaling. Clinical studies have revealed a bidirectional vicious cycle between osteoporosis and Alzheimer’s disease: reduced bone density exacerbates Alzheimer’s disease pathology through pathways such as PDGF-BB, while AD-related neurodegeneration further accelerates bone loss. The breakthrough lies in the discovery that anti-osteoporotic drugs, such as bisphosphonates, improve cognitive function. In contrast, neuroactive drugs modulate bone metabolism, providing new strategies for the treatment of comorbid conditions. Additionally, whole-body vibration therapy shows potential for non-pharmacological interventions by modulating bone-brain interactions through the mechano-osteoclast signaling axis. In the future, it will be essential to integrate multiple groups of biomarkers to develop early diagnostic tools that promote precise prevention and treatment of bone-brain comorbidities. This article provides a new perspective on the mechanisms and therapeutic strategies of neuroskeletal comorbidities. Full article

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the organization, mechanisms of action, and clinical implications of cerebral RAS in physiological conditions and in various neurological pathologies. The cerebral RAS operates autonomously, synthesizing its main components locally due to restrictions imposed by the blood–brain barrier. The key elements of the system are (pro)renin; (pro)renin receptor (PRR); angiotensinogen; angiotensin-converting enzyme types 1 and 2 (ACE1 and ACE2); angiotensin I (AngI), angiotensin II (AngII), angiotensin III (AngIII), angiotensin IV (AngIV), angiotensin A (AngA), and angiotensin 1-7 (Ang(1-7)) peptides; RAS-regulating aminopeptidases; and AT1 (AT1R), AT2 (AT2R), AT4 (AT4R/IRAP), and Mas (MasR) receptors. More recently, alamandine and its MrgD receptor have been included. They are distributed in specific brain regions such as the hypothalamus, hippocampus, cerebral cortex, and brainstem. The system is organized into two opposing axes: the classical axis (renin/ACE1/AngII/AT1R) with vasoconstrictive, proinflammatory, and prooxidative effects, and the alternative axes AngII/AT2R, AngIV/AT4R/IRAP, ACE2/Ang(1-7)/MasR and alamandine/MrgD receptor, with vasodilatory, anti-inflammatory, and neuroprotective properties. This functional duality allows us to understand its role in neurological physiopathology. RAS dysregulation is implicated in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and neuropsychiatric disorders such as depression and anxiety. In brain aging, an imbalance toward hyperactivation of the renin/ACE1/AngII/AT1R axis is observed, contributing to cognitive impairment and neuroinflammation. Epidemiological studies and clinical trials have shown that pharmacological modulation of the RAS using ACE inhibitors (ACEIs) and AT1R antagonists (ARA-II) not only controls blood pressure but also offers neuroprotective benefits, reducing the incidence of cognitive decline and dementia. These effects are attributed to direct mechanisms on the CNS, including reduction of oxidative stress, decreased neuroinflammation, and improved cerebral blood flow. Full article

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Although conventional therapies are effective in controlling symptoms, they remain limited in altering the course of the disease and significantly reducing the chronic inflammation and oxidative stress underlying it. In this context, nanoparticles and nanomaterials are emerging as innovative tools capable of overcoming traditional pharmacological barriers due to their ability to deliver therapeutic oligonucleotides, antioxidants, and drugs in a targeted manner, modulate immune responses, and improve the bioavailability of active compounds. In particular, metal–organic frameworks (MOFs) stand out as ideal candidates for inhalable drug delivery in COPD, owing to their permanent crystalline porous structure, high specific surface area, and versatile chemical functionalization. This review provides the most recent preclinical evidence on the use of different nanoparticles in COPD, with a focus on the therapeutic and diagnostic potential of MOFs. It discusses their biocompatibility, drug loading strategies, and controlled release mechanisms and explores future perspectives for clinical translation. Full article

Artesunate (AS) and tetramethylpyrazine (TMP) have been proven to have therapeutic potential in ischemic stroke. Nevertheless, their synergistic treatment mechanisms and effectiveness remain unclear. A rat MCAO model was induced, and AS, combined with TMP, was administered intranasally to rats once a day for 3 days. The neurological severity scores, TTC staining, and H&E staining were implemented to analyze tissue injuries. Evans blue staining and immunohistochemistry of ZO-1, occludin, MMP-9, and TIMP-1 were implemented to evaluate the integrity of the blood–brain barrier (BBB). ELISA was used to detect the expression levels of inflammatory factors TNF-α and IL-10. TUNEL staining and the protein expression of Bax and Bcl-2 were used to evaluate the apoptosis of brain tissue cells. The core targets were predicted by network pharmacology and verified by the OGD/R cell model and siRNA in vitro. Results showed that nasal administration of AS and TMP significantly ameliorated ischemic-stroke-induced neurological dysfunction, BBB disruption, and cortical neuronal apoptosis. The protective mechanisms mainly included adjusting the expression and ratio of tight junction proteins TIMP-1 and MMP-9 in brain tissue, regulating the HIF-1α-VEGF pathway, and anti-inflammatory effects. This study provides experimental support for the further development and application of AS and TMP nasal combinations and provides the foundation for expanding the practical-application value of artemisinin and its derivatives. Full article

Background: Type 2 diabetes (T2D) has become a serious global public health concern. Liubao tea (LBT) has demonstrated beneficial effects on gut microbiota and glucose-lipid metabolism, holding promising therapeutic potential for T2D; however, its underlying mechanisms remain unclear. This study aims to elucidate the potential mechanisms of Liubao tea extract (LBTE) against T2D. Methods: LC-MS technology was used to identify the chemical components of LBTE and combined with network pharmacology and molecular docking to screen its potential active ingredients and targets for improving T2D. Therapeutic efficacy was assessed in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice via serum biochemical analyses and histopathological examinations. Serum metabolomics, 16S rRNA sequencing, quantification of short-chain fatty acids (SCFAs), quantitative real-time PCR (qPCR), and antibiotic-treated pseudo-germ-free models were employed to elucidate the underlying mechanisms. Results: LBTE effectively reduced blood glucose levels and improved lipid metabolism, primarily by promoting hepatic glycogen synthesis and suppressing glycerophospholipid synthesis. LBTE also alleviated hepatic inflammation by modulating inflammatory cytokine expression. Additionally, LBTE reshaped the gut microbiota profiles by decreasing harmful bacteria and increasing SCFA-producing bacteria, resulting in elevated fecal SCFAs. SCFAs contributed to improving hepatic metabolism and inflammation, enhancing intestinal barrier function. Notably, these effects were abolished by antibiotic-induced microbiota depletion, confirming the microbiota-dependent mechanism of LBTE. Quercetin, luteolin, genistein, and kaempferol were considered as potential active ingredients contributing to the antidiabetic effects of LBTE. Conclusions: These findings provide novel perspectives on the viability of LBTE as a complementary strategy for T2D prevention and management. Full article

As a highly disabling chronic inflammatory disease, rheumatoid arthritis (RA) necessitates novel interventions. Liupao tea is a traditional Chinese dark tea known for its favorable anti-inflammatory properties. This study aims to elucidate the active ingredients and action mechanisms underlying the therapeutic effects of Liupao tea extract (LPTE) in RA. LPTE was preliminarily characterized by LC-MS technology. Network pharmacology and molecular docking predicted anti-RA compounds, targets, and pathways, with key compounds identified using chemical standards. The effect of LPTE on the collagen-induced arthritis mouse model was evaluated through serum biochemical analysis, micro-CT imaging, and histopathological analyses. Integrated serum metabolomics, 16S rRNA sequencing, MetOrigin analysis, SCFA metabolomics, and quantitative real-time PCR elucidated gut–joint axis mechanisms. LPTE effectively attenuated RA symptoms by reducing bone destruction and joint inflammation. Notably, LPTE reshaped gut microbiota by enriching key families such as Monoglobaceae, Eggerthellaceae, and Desulfovibrionaceae, thereby promoting SCFA production. Increased SCFA levels enhanced intestinal barrier integrity and exerted joint-protective and anti-inflammatory effects by upregulating tight junction proteins and activating SCFA receptors. LPTE also modulated arachidonic acid metabolism by affecting key genes such as Alox5, Ptgs2, and Cbr1. These effects collectively reduced the levels of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in joints. Additionally, quercetin, luteolin, ellagic acid, and kaempferol were identified as major anti-RA bioactive compounds in LPTE. Taken together, this study provides preliminary evidence that LPTE mitigates RA by regulating the gut–joint axis mediated via fatty acid metabolism. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by immune dysregulation and epidermal barrier dysfunction. Advances in understanding the interplay of genetic predisposition, cytokine signaling, and environmental triggers have led to the emergence of targeted therapies. Although biologic agents such as dupilumab, tralokinumab, and lebrikizumab have revolutionized AD management, their high costs, injectable administration, and limited global accessibility highlight the need for alternative options. Small molecule therapies are gaining momentum as they target intracellular pathways central to AD pathogenesis and offer oral or topical administration routes. This review provides a comprehensive analysis of key agents including Janus kinase (JAK) inhibitors (upadacitinib, abrocitinib, baricitinib, ruxolitinib, delgocitinib), phosphodiesterase 4 (PDE4) inhibitors (crisaborole, difamilast, roflumilast, apremilast), as well as STAT6 degraders (KT621, NX3911), aryl hydrocarbon receptor modulators, histamine H4 receptor antagonists (adriforant, izuforant), and sphingosine-1-phosphate receptor modulators (etrasimod, BMS-986166). We summarize their mechanisms of action, pharmacological profiles, and pivotal clinical trial data, emphasizing their potential to address unmet therapeutic needs. Finally, we discuss safety concerns, long-term tolerability, and future directions for integrating small molecule therapies into precision treatment strategies for moderate-to-severe AD. Full article

Hederagenin, a pentacyclic triterpenoid saponin from various medicinal plants, shows immense therapeutic potential; however, its inherent low bioavailability severely hinders its clinical translation. This comprehensive review synthesizes recent studies on the health benefits of hederagenin and its glycosides, critically the chemical modification strategies and pharmacological mechanisms aimed at optimizing its bioactivity. Key findings reveal that its broad anticancer and anti-inflammatory activities largely stem from its capacity to modulate crucial cellular signaling pathways, including the NF-κB, PI3K/Akt, and MAPK. Structural modification, particularly intelligent derivatization at the C-28 position, is a central strategy to overcome its pharmacokinetic deficiencies and significantly boost cytotoxicity. Furthermore, its unique pro-oxidant function within cancer cells, achieved by inhibiting the Nrf2-ARE antioxidant pathway, offers a novel approach for selective chemotherapeutics. For the clinical translation of hederagenin, we propose a strategic focus on derivatization through multi-target hybrids and sophisticated delivery systems. This approach is essential for addressing its pharmacokinetic barriers while strategically leveraging its context-dependent pro-oxidant effects. Full article

Odontophobia, defined as the intense and persistent fear of dentists or dental care, is a widely underestimated, yet clinically significant, barrier to oral health. It affects individuals across all age groups, from children to the elderly, and is particularly prevalent among those with intellectual or developmental disabilities. Odontophobia is a multifactorial condition influenced by psychological, sensory, cognitive, and sociocultural factors. Left unaddressed, it contributes to poor oral health outcomes, avoidant behavior, and broader health disparities. This perspective paper explores the clinical manifestations and principles of management of odontophobia across populations and different age groups, highlighting the limitations of pharmacological sedation, especially when used in isolation. Instead, evidence supports the use of cognitive behavioral strategies, desensitization protocols, sensory-adaptive environments, and communication-based approaches, such as the “tell-show-do” method. Innovative technologies, including virtual reality, offer additional promise. This paper also addresses critical gaps in the research, the paucity of tailored interventions for vulnerable groups, and both ethical and legal complexities surrounding consent, autonomy, and equitable access. Ultimately, managing odontophobia requires a shift toward “person-centered” and “trauma-informed” dental care, supported by interdisciplinary collaboration, inclusive infrastructure, and policy-level commitment to reduce fear-based disparities in oral health. Full article

Obesity is a well-established risk factor for both the incidence and poorer clinical outcomes of Breast Cancer (BC), particularly among hormone receptor-positive postmenopausal women. However, conventional weight loss interventions have yielded limited success in altering cancer prognosis. Recently, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide and tirzepatide, have emerged as effective pharmacologic agents for sustained weight loss and are under investigation in oncology. This narrative review synthesizes evidence linking obesity to poor BC prognosis and evaluates the therapeutic potential of GLP-1 RAs in this context. Mechanistically, obesity exacerbates tumor progression through hormonal imbalance, chronic inflammation, and adipokine and insulin signaling, targets that may be modifiable through weight reduction. GLP-1 RAs offer multiple benefits, such as appetite suppression, delayed gastric emptying, and enhanced insulin sensitivity. Clinical studies in BC patients have shown weight loss ranging from 2.3% to 5%, likely attenuated by concurrent endocrine therapy. Preliminary data suggest that GLP-1 RA use does not increase the risk of cancer recurrence and may reduce cardiovascular morbidity. However, prospective studies are needed to confirm long-term oncologic safety and efficacy. Disparities in access and cost remain barriers to widespread adoption. Nevertheless, GLP-1 RAs represent a promising adjunct to manage obesity among BC patients, potentially improving metabolic health and long-term cancer outcomes. Full article

Obesity presents a significant barrier to transplant eligibility due to increased morbidity associated with higher BMI. Patients with obesity who undergo transplantation face elevated risks of perioperative complications, morbidity from metabolic disease, and delayed graft function. However, recent advances in metabolic and bariatric medicine, endoscopy, and surgery offer promising opportunities for integration with transplant care. This critical review explores the potential benefits of metabolic and bariatric interventions for at-risk transplant patients. Here, we will briefly discuss the implications of obesity in transplant patients, pharmacologic, surgical, and endoscopic interventions, and ultimately, the role of bariatric surgery in different solid organ transplants. The successful implementation of these approaches could dramatically expand access to solid organ transplantation, creating life-saving opportunities for patients who would otherwise be deemed ineligible for this essential treatment. Despite the implications of metabolic and bariatric interventions in transplant care, this review is limited by the need for long-term studies of outcomes to better understand the effects of graft survival and durability of changes in metabolic syndromes. Full article

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease of the central nervous system, responsible for 60–80% of dementia. Its pathogenesis is mainly based on the accumulation of beta-amyloid and tau proteins. Current pharmacological treatment includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies. However, their effect is limited by the blood–brain barrier (BBB). A new and promising way for different drugs to cross the BBB is the use of nanoparticles such as liposomes, micelles, solid lipid nanocarriers, polymeric nanoparticles, dendrimers, nanoemulsions, and inorganic nanoparticles as their carriers. Additionally, some nanoparticles present anti-inflammatory or neuroprotective effects. Some of them can also be used to treat cerebral amyloid angiopathy (CAA) by aiming at amyloid deposits in brain arterioles. All the properties of nanoparticles listed and discussed in the article allow us to hope that there will be more effective treatment in the future, which is extremely important as the number of patients with AD is still growing. Full article

This study aimed to evaluate the protective effects of Inula japonica leaf extract against PM₁₀-induced oxidative stress in normal human keratinocytes. Keratinocytes were pretreated with various concentrations of Inula japonica leaf extract and subsequently exposed to PM10. Cell viability, ROS production, gene and protein expression (qRT-PCR and Western blot), and UHPLC-MS profiling were assessed. Network pharmacology analysis was conducted using database-predicted compounds of Inulae Flos. The extract significantly reduced PM₁₀-induced ROS generation and restored the expression of epidermal barrier-related genes such as loricrin. It also inhibited phosphorylation of MAPKs (ERK, p38) and modulated apoptotic and inflammatory markers including Bax, p53, MMP-9, and COX-2. UHPLC-MS analysis identified eight compounds not previously reported in our earlier study, which may contribute to the extract’s protective effects. Inula japonica leaf extract exerts protective effects against PM₁₀-induced skin damage by reducing oxidative stress and inflammation in keratinocytes. These findings support its potential as a therapeutic candidate for pollution-related skin disorders. Full article

Anxiety and depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD), which can contribute to increased morbidity, reduced quality of life, and worse clinical outcomes. Nevertheless, these psychological conditions remain largely overlooked. This narrative review includes studies published between 1983 and 2025 to synthesise the current evidence on the risk factors, clinical impacts, and therapeutic strategies for these comorbidities. While the exact mechanisms leading to their increased prevalence are not fully understood, growing evidence implicates a combination of biological (e.g., systemic inflammation), social (e.g., isolation and stigma), and behavioural (e.g., smoking and inactivity) factors. Despite current guidelines recommending the identification and management of these comorbidities in COPD, they are not currently included in COPD assessments. Undetected and unmanaged anxiety and depression have serious consequences, including poor self-management, non-adherence to medications, increased risk of exacerbation and hospitalisations, and even mortality; thus, there is a need to incorporate screening as part of COPD assessments. There is robust evidence showing that pulmonary rehabilitation, a core non-pharmacological intervention, can improve mood symptoms, enhance functional capacity, and foster psychosocial resilience. Psychological therapies such as cognitive behavioural therapy (CBT), mindfulness-based approaches, and supportive counselling have also demonstrated value in reducing emotional distress and improving coping mechanisms. Pharmacological therapies, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed in moderate to severe cases or when non-pharmacological approaches prove inadequate. However, the evidence for their efficacy in COPD populations is mixed, with concerns about adverse respiratory outcomes and high discontinuation rates due to side effects. There are also barriers to optimal care, including underdiagnosis, a lack of screening protocols, limited provider training, stigma, and fragmented multidisciplinary coordination. A multidisciplinary, biopsychosocial approach is essential to ensure early identification, integrated care, and improved outcomes for patients with COPD. Full article

Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central nervous system (CNS) applications, including brain malignancies such as gliomas and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Microtubule-stabilizing agents, such as taxanes and epothilones, promote microtubule assembly and have shown efficacy in both tumour suppression and neuronal repair, though their CNS use is hindered by blood–brain barrier (BBB) permeability and neurotoxicity. Destabilizing agents, including colchicine-site and vinca domain binders, offer potent anticancer effects but pose greater risks for neuronal toxicity. This review highlights the mapping of nine distinct tubulin binding pockets—including classical (taxane, vinca, colchicine) and emerging (tumabulin, pironetin) sites—that offer new pharmacological entry points. We summarize the recent advances in structural biology and drug design, enabling MTAs to move beyond anti-mitotic roles, unlocking applications in both cancer and neurodegeneration for next-generation MTAs with enhanced specificity and BBB penetration. We further discuss the therapeutic potential of combination strategies, including MTAs with radiation, histone deacetylase (HDAC) inhibitors, or antibody–drug conjugates, that show synergistic effects in glioblastoma models. Furthermore, innovative delivery systems like nanoparticles and liposomes are enhancing CNS drug delivery. Overall, MTAs continue to evolve as multifunctional tools with expanding applications across oncology and neurology, with future therapies focusing on optimizing efficacy, reducing toxicity, and overcoming therapeutic resistance in brain-related diseases. Full article