Biomedicines最新文献

{"title":"Anti-Inflammatory and Analgesic Properties of <i>Polygonum minus</i>: Mechanistic Insights and Therapeutic Potential.","authors":"Mohd Amir Kamaruzzaman, Ruzaidi Ruslan, Isma Liza Mohd Isa, Nur Aqilah Kamaruddin, Elvy Suhana Mohd Ramli","doi":"10.3390/biomedicines14092070","DOIUrl":"10.3390/biomedicines14092070","url":null,"abstract":"<p><p>Inflammation is a complex protective biological response triggered by harmful stimuli such as pathogens, chemical agents, or physical injury, and is closely associated with the development of pain and various chronic diseases. It involves a coordinated cascade of cellular and molecular events, including activation of pattern recognition receptors, release of pro-inflammatory cytokines, production of reactive oxygen species, and recruitment of immune cells. Acute inflammation is essential for host defense and tissue repair. However, persistent or dysregulated inflammation may lead to chronic inflammation, oxidative stress, and tissue damage. Inflammatory pain, a subtype of nociceptive pain, arises from the sensitization of peripheral and central nociceptive pathways by inflammatory mediators such as cytokines, prostaglandins, and nitric oxide. Herbal products have been traditionally used to manage inflammatory diseases due to their bioactive compounds, which modulate inflammatory pathways and alleviate symptoms, and gaining increasing attention due to their multi-targeted mechanisms and lower adverse effects. <i>Polygonum minus</i> (PM), a medicinal herb widely used in Southeast Asia, is rich in bioactive compounds including flavonoids, phenolics, polygodial and essential oils. Phytochemical studies have identified compounds such as qsiuercetin and myricetin, which exhibit strong antioxidant and anti-inflammatory properties. Experimental evidence suggested that <i>PM</i> exerts its anti-inflammatory effects through the inhibition of key inflammatory pathways, including cyclooxygenase (COX) and lipoxygenase (5-LOX), suppression of pro-inflammatory cytokines, and modulation of nuclear factor-kappa B (NF-κB) signaling. Additionally, its antioxidant activity contributes to the reduction in oxidative stress, thereby limiting inflammation-induced tissue damage. This review highlights the mechanisms the potential therapeutic role of PM in modulating underlying inflammation and inflammatory pain. The evidence suggested that PM may serve as a potential promising natural agent for the management of inflammation and pain. Further studies are warranted to elucidate its molecular mechanisms and to validate its efficacy and safety in clinical settings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The vWF/ADAMTS13 Ratio as a Potential Marker of Endotheliopathy in Malignancies.","authors":"Alexander Vorobev, Victoria Bitsadze, Jamilya Khizroeva, Antonina Solopova, Maria Tretyakova, Nilufar Gashimova, Kristina Grigoreva, Irina Kalashnikova, Natalia Makatsariya, Vlada Rubashkina, Yana Sulina, Aidanhanum Iskenderova, Alexandra Antonova, Dmitry Utkin, Jean-Christophe Gris, Ismail Elalamy, Grigoris Gerotziafas, Alexander Makatsariya","doi":"10.3390/biomedicines14092078","DOIUrl":"10.3390/biomedicines14092078","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Endothelial activation and thromboinflammation play an important role in cancer-associated thrombosis. An imbalance between von Willebrand factor (vWF) and its physiological regulator ADAMTS13 may reflect the development of a prothrombotic endothelial state in patients with malignancies. However, the dynamics of the vWF-ADAMTS13 axis during chemotherapy and thromboprophylaxis remain insufficiently characterized. &lt;b&gt;Objectives:&lt;/b&gt; To characterize the vWF-ADAMTS13 axis as a potential laboratory marker of endotheliopathy in patients with gynecologic malignancies and to assess its dynamics during chemotherapy and thromboprophylaxis with low-molecular-weight heparin (LMWH). &lt;b&gt;Materials and Methods:&lt;/b&gt; This prospective comparative study included 74 patients with stage I-III gynecologic malignancies undergoing chemotherapy after surgical treatment. Group I comprised 34 patients with a history of thrombotic complications (VTE), including 23 patients with ovarian cancer and 11 with cervical adenocarcinoma. Group II included 40 patients without previous VTE, including 20 patients with ovarian cancer and 20 with cervical adenocarcinoma. The control group consisted of 25 healthy women. Plasma vWF levels, ADAMTS13 antigen and functional activity, ADAMTS13 inhibitor levels, and the vWF/ADAMTS13 ratio were assessed before chemotherapy and after 1-2 chemotherapy cycles. Patients in Group I additionally received thromboprophylaxis with nadroparin calcium. &lt;b&gt;Results:&lt;/b&gt; Before chemotherapy, an imbalance of the vWF-ADAMTS13 axis was observed in patients with malignancies compared with healthy controls and was most pronounced in patients with a history of thrombosis. The vWF/ADAMTS13 ratio was 0.65 in controls, 1.02 and 0.84 in patients without previous VTE with ovarian and cervical cancer, respectively, and 1.59 and 1.34 in the corresponding subgroups with a history of thrombosis (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). After 1-2 chemotherapy cycles, the vWF-ADAMTS13 axis showed a further shift toward imbalance, characterized by increased vWF levels, decreased ADAMTS13 antigen levels and functional activity, and increased ADAMTS13 inhibitor concentrations. The vWF/ADAMTS13 ratio increased to 2.04 in patients with ovarian cancer and to 1.65 in those with cervical cancer and a history of thrombosis. In Group I, the subsequent assessment following chemotherapy and LMWH thromboprophylaxis demonstrated partial reversal of these changes: ADAMTS13 antigen levels increased, while vWF levels and ADAMTS13 inhibitor concentrations decreased, and the vWF/ADAMTS13 ratio declined from 2.04 to 1.30 in ovarian cancer and from 1.65 to 1.14 in cervical cancer. &lt;b&gt;Conclusions:&lt;/b&gt; The vWF-ADAMTS13 axis is markedly altered in patients with gynecologic malignancies, including those without previous VTE, with the most pronounced imbalance observed in patients with a history of thrombosis. The post-chemotherapy assessment demonstrated a further shift toward imbalance, whereas the","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Evaluation of HHLA2 in Hormone Receptor-Positive Breast Cancer: Expression Patterns and Prognostic Implications.","authors":"Mi Jung Kwon, Joo Mi Yi, Tae Hyun Kim, Ha Young Park","doi":"10.3390/biomedicines14092066","DOIUrl":"10.3390/biomedicines14092066","url":null,"abstract":"<p><p><b>Background:</b> HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) is a B7 family immune checkpoint molecule that delivers costimulatory or coinhibitory signals depending on the receptor engaged. Although it has been implicated in various cancers, its clinical significance in hormone receptor (HR)-positive breast cancer remains unclear. <b>Methods:</b> Ninety-three patients with HR-positive breast cancer who underwent surgical resection were analyzed using tissue microarrays. HHLA2 expression was assessed by immunohistochemistry using a combined intensity and proportion score (0-8), analyzed as a continuous variable by Cox regression, with dichotomized comparisons (score >5 vs. ≤5) as sensitivity analyses. Associations with clinicopathologic variables were evaluated using Fisher's exact test and Spearman correlation. A complementary analysis was performed using RNA-sequencing data from the TCGA-BRCA cohort. <b>Results:</b> HHLA2 immunoreactivity was detected in 86 tumors (92.5%). No significant associations were identified between HHLA2 expression and age, tumor size, nodal status, grade, or HER2 status. The HHLA2 score was not associated with overall, disease-specific, or relapse-free survival (hazard ratio per 1-point increase 1.17, 1.86, and 1.19, respectively; all <i>p</i> > 0.1), and no cutoff reached significance after correction for multiple comparisons. In TCGA-BRCA, HHLA2 transcript levels were low overall and higher in triple-negative than in HR-positive tumors (<i>p</i> < 0.001), but were not associated with survival in either group. <b>Conclusions:</b> HHLA2 immunoreactivity was detected in most HR-positive breast cancers, but no association with clinicopathologic features or survival was detected in this small exploratory cohort. Larger studies are needed to exclude modest prognostic effects.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Exosomal miRNA-mRNA Regulatory Network Relevant to Tuberculous-Associated Lung Cancer.","authors":"Hyun-Jung Kang, Goeun Park, Yoonki Hong, Byung-Chul Kim, Hyowon Park, Jae Jun Lee, Seung-Ho Shin, Ji Young Hong","doi":"10.3390/biomedicines14092060","DOIUrl":"10.3390/biomedicines14092060","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Tuberculosis is a risk factor for lung cancer. Previous studies have demonstrated that miRNAs derived from tuberculous pleural effusion (TPE) exosomes are involved in lung cancer progression. This study aimed to identify potential miRNA-mRNA regulatory networks associated with TPE-derived exosome exposure in the context of lung cancer. <b>Methods</b>: Exploratory differential expression analysis was performed using RNA-seq data from TPE-derived exosomes to select candidate miRNAs showing differential expression patterns. In an in vivo mouse xenograft tumor model, TPE-derived exosomes were administered intratumorally, followed by RNA-seq analysis to select candidate genes showing differential expression patterns. Predicted target genes of the candidate miRNAs were then overlapped with the candidate genes from the xenograft analysis to obtain overlapping common genes (OCGs). The regulation of these genes by candidate miRNAs was validated through in vitro experiments, and a miRNA-mRNA network was constructed using Cytoscape. <b>Results</b>: Exploratory analyses suggested differential expression patterns in 27 candidate miRNAs (19 showing increased and 8 showing decreased expression) in TPE-derived exosomes and 2340 candidate genes in xenograft tissues. A total of 4715 and 700 target genes were predicted for candidate miRNAs using miRDB and miRTarBase, respectively. Following a stepwise filtering strategy, five candidate target genes (<i>RRAS2</i>, <i>RAC1</i>, <i>RAP1B</i>, <i>NOTCH2</i>, and <i>SMARCA4</i>) were prioritized from the overlapping common genes (OCGs). The seven candidate miRNAs predicted to regulate these genes were subsequently used to prioritize a candidate 7-miRNA-5-mRNA regulatory network for further investigation. <b>Conclusions</b>: This study prioritized a candidate miRNA-mRNA regulatory network associated with TPE-derived exosome exposure in lung cancer models, providing a basis for further investigation in larger clinical cohorts and more physiologically relevant models.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REDD1 Silencing Aggravates Aortic Dissection and Promotes VSMC Apoptosis with Autophagy-Related Changes.","authors":"Bolai Shen, Xiaoping Xie, Qinyu Chen, Yang Zhou, Jiangxiong Wu, Bowen Li, Zhiwei Wang","doi":"10.3390/biomedicines14092061","DOIUrl":"10.3390/biomedicines14092061","url":null,"abstract":"<p><p><b>Background:</b> Aortic dissection (AD) is a life-threatening vascular disease with high mortality, yet its molecular pathogenesis remains incompletely understood. This study investigated the role of regulated in development and DNA damage responses 1 (REDD1) in vascular smooth muscle cells (VSMCs) apoptosis and the underlying mechanisms. <b>Methods:</b> Single-cell RNA sequencing data from GSE222318 were analyzed to investigate the expression levels of REDD1 in VSMCs and its role in inducing apoptosis and autophagy. The target gene was silenced in C57BL/6J mice via tail-vein injection of Adeno-associated virus.β-aminopropionitrile (BAPN) was used for AD induction. Western blotting was used to assess REDD1, LC3B, p62, BAX, BCL-2 in aortic tissues. Aortic histopathological alterations were examined by hematoxylin and eosin (H&E), Elastica van Gieson (EVG), and Masson's trichrome staining. Immunofluorescence was performed to examine REDD1 expression and its localization in α-SMA-positive vascular smooth muscle cells. REDD1, LC3B, p62, BAX, BCL-2, mTOR, and p-mTOR were also examined by Western blotting in cultured cells. Mitochondrial membrane potential was evaluated by JC-1 staining, and apoptosis was assessed by flow cytometry. <b>Results:</b> REDD1 expression levels were significantly increased in human AD tissues and localized predominantly to medial VSMCs. REDD1 levels were positively correlated with BAX and LC3B and negatively correlated with BCL-2 and p62. Knockdown of REDD1 in AD mice was associated with increased levels of BAX and p62 and decreased levels of BCL-2 and LC3B in aortic tissues, accompanied by more severe pathological manifestations. REDD1 silencing in VSMCs increased BAX, p62 and p-mTOR while reducing BCL-2 and LC3B, accompanied by increased apoptosis and loss of mitochondrial membrane potential, whereas rapamycin reduced apoptosis and alleviated mitochondrial injury. <b>Conclusions:</b> REDD1 appears to play a protective, compensatory role in AD. Increased REDD1 expression may help preserve mitochondrial membrane potential and attenuate VSMC apoptosis under pathological stress, accompanied by changes in static autophagy-related markers that suggest a possible association with increased autophagic activity. Loss of REDD1 activity promotes mitochondrial injury and VSMC apoptosis, thereby aggravating AD. Targeting REDD1 may therefore represent a potential therapeutic strategy for AD.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Evidence for a Putative B Cell-Cholate Immunometabolic Axis in Pericarditis: A Mendelian Randomization Study.","authors":"Yifei Zhang, Wuxiao Yang, Xuewen Li","doi":"10.3390/biomedicines14092063","DOIUrl":"10.3390/biomedicines14092063","url":null,"abstract":"<p><p><b>Background:</b> Pericarditis is an inflammatory heart disease with unclear causal mechanisms. Immune dysregulation is implicated, but observational studies cannot reliably infer causality. Whether plasma metabolites mediate immune-pericarditis pathways remains unknown. <b>Methods:</b> A two-sample Mendelian randomization (MR) study was performed using publicly available summary-level genome-wide association study data. Genetic instruments were selected via significance screening, linkage disequilibrium clumping, and strength evaluation (F-statistic > 10). A relaxed instrument selection threshold of <i>p</i> < 1 × 10^-5 was used for immunophenotypes and metabolites, and a threshold of <i>p</i> < 5 × 10^-6 was applied for pericarditis in reverse MR. Forward MR assessed potential causal effects of immune cells and metabolites on pericarditis; reverse MR tested the opposite direction. Two-step mediation MR evaluated whether metabolites mediated immune-to-pericarditis pathways. The primary method was inverse variance weighting (IVW), complemented by a range of sensitivity analyses. <b>Results:</b> A total of 18,621 SNPs served as instruments for immunophenotypes and 34,843 for metabolites. Forward MR identified 29 immunophenotypes with genetically predicted associations with pericarditis (20 risk, 9 protective). Reverse MR identified 13 immunophenotypes associated with genetic susceptibility to pericarditis, indicating a bidirectional genetic architecture. Ten plasma metabolites showed genetically predicted associations with pericarditis. After false discovery rate (FDR) correction, these key associations remained significant. Mediation analysis identified a putative immunometabolic pathway in which CD25 on IgD+ CD38br B cells increased pericarditis risk partly through downregulation of the protective metabolite cholate (β₁ = -0.114, <i>p</i> = 0.002; β₂ = -0.419, <i>p</i> = 0.001). The indirect effect was 0.048 (95% CI: 0.012 to 0.097), accounting for 32.8% of the total effect. All key results were robust in sensitivity analyses. <b>Conclusions:</b> This study provides genetic evidence supporting a putative immune cell-metabolite-pericarditis pathway involving CD25-positive B cells and cholate, and suggests potential immunometabolic targets for future investigation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphedema Is Associated with Mitral Annular Abnormalities-A Three-Dimensional Speckle-Tracking Echocardiographic Analysis from the MAGYAR-Path Study.","authors":"Attila Nemes, Nóra Ambrus, Lajos Kemény, Győző Szolnoky","doi":"10.3390/biomedicines14092062","DOIUrl":"10.3390/biomedicines14092062","url":null,"abstract":"<p><p><b>Introduction:</b> Lymphedema is a chronic, progressive disorder characterized by the excessive accumulation of lymphatic fluid within the interstitial compartment resulting from impaired lymphatic transport. Consequently, the primary aim of the present study was to evaluate three-dimensional speckle-tracking echocardiography (3DSTE)-derived mitral annular (MA) morphology and function in patients with lymphedema, and to compare these parameters with those of age- and sex-matched healthy controls. Associations between MA parameters and regional LV strains were also assessed. Furthermore, it was investigated whether one-hour use of medical compression stockings (MCSs) exerts acute effects on MA geometry and function and regional LV strains in lymphedema. <b>Methods:</b> The study included 24 patients with lymphedema (mean age: 48.0 ± 11.2 years, 23 females) without known cardiovascular symptoms. Their results were compared to those of 45 healthy individuals (mean age: 42.1 ± 13.9 years, all females) with a similar mean age value and gender ratio. Patients and controls had no traditional cardiovascular risk factors. All patients and control subjects underwent conventional M-mode and two-dimensional Doppler echocardiography extended with 3DSTE. <b>Results:</b> At rest, radial and circumferential strains (LV-RS and LV-CS, respectively) tended to increase across most LV regions, except for basal LV-RS. Conversely, longitudinal contraction, represented by LV longitudinal strain (LV-LS) was reduced in the basal LV region but tended to increase in the midventricular and apical regions. This distinct contractile pattern was accompanied by reduced end-diastolic MA dimensions, whereas end-systolic parameters remained unchanged, consequently leading to impaired MA sphincter-like function. While most regional LV strains shifted toward control values following MCS use-except for basal and apical LV-RS and midventricular and apical LV-LS-end-diastolic MA dimensions simultaneously demonstrated a similar trend, culminating in an improvement in MA functional properties. <b>Conclusions:</b> The presented exploratory findings suggest that lymphedema may be associated with alterations in end-diastolic MA dimensions and a consequent impairment of MA function, which appear to be accompanied by specific regional LV functional abnormalities. Furthermore, one-hour MCS use was observed to exert acute, directional shifts in these imaging-derived surrogate parameters.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapting Tension-Type Headache to the International Association for the Study of Pain (IASP) Taxonomy: A Conceptual Proposal.","authors":"Margarita Cigarán-Mendez, Juan C Pacho-Hernández, Angela Tejera-Alonso, Cristina Gómez-Calero, Lars Arendt-Nielsen, Jo Nijs, César Fernández-de-Las-Peñas","doi":"10.3390/biomedicines14092058","DOIUrl":"10.3390/biomedicines14092058","url":null,"abstract":"<p><p>Tension-type headache (TTH) is a primary headache characterized by treatment effect heterogeneity, possibly reflecting variations in underlying pain mechanisms. Identifying pain phenotyping or classifying patients into subgroups based on their predominant pain mechanism may provide targeted treatment options. This paper proposes a conceptual adaptation of the International Association for the Study of Pain (IASP) clinical criteria to identify the predominant phenotype in individuals with TTH. It has been found that pain referrals elicited by trigger points (TrPs) reproduce headache symptoms in patients with TTH. Since preliminary studies suggest that TrPs can represent a peripheral nociceptive input, this could lead to considering TTH as a potential nociceptive condition. However, TrP treatment has limited short-term effects for reducing headache frequency, intensity or duration, requiring us to look beyond this possible peripheral driver. Thus, patients with TTH exhibit altered nociceptive processing, which is compatible with nociplastic pain features. Arguably, treatment approaches for nociplastic phenotypes should address maladaptive factors associated with altered nociceptive processing. Based on the current conceptual proposal, TTH should not be viewed as a homogeneous condition but rather as a spectrum in which nociceptive and nociplastic phenotypes coexist with different predominance according to the disease stage and severity. Collectively, it seems that nociceptive and nociplastic mechanisms may contribute to TTH across its clinical spectrum, with nociplastic features appearing to become more prominent in patients with the chronic form of headache. Recognizing the coexistence of nociceptive and nociplastic pain mechanisms may facilitate precision pain management and improve treatment selection in phenotype patients with TTH. In either case, future trials should identify treatment options with long-term effects for TTH, as currently used approaches only yield short-term benefits.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Arteriosclerosis and Fundus Photograph-Defined Glaucoma in Young Adults: Findings from the Gangnam Eye Cohort.","authors":"Eunoo Bak, Jin-Soo Kim, Dae Joong Ma, Jinho Lee, Baek Lok Oh, Hyuk Jin Choi","doi":"10.3390/biomedicines14092059","DOIUrl":"10.3390/biomedicines14092059","url":null,"abstract":"<p><p><b>Background/Objectives</b>: To evaluate systemic and ocular factors associated with glaucoma in young adults using data from a large health screening cohort. <b>Methods</b>: This cross-sectional observational study analyzed baseline data from 16,002 Korean adults younger than 40 years (range, 18-39 years) in the Gangnam Eye Cohort. Participants underwent comprehensive health screening examinations, including standardized ophthalmic evaluation and fundus photography. Glaucoma was defined by structural glaucomatous changes on fundus photographs, and retinal arteriosclerosis was graded using a modified Scheie classification. Univariable and multivariable logistic regression models were used to identify factors associated with glaucoma. <b>Results</b>: Among 16,002 participants, 257 (1.61%) were classified as having glaucoma; 186 of these participants (72.4%) had unilateral glaucoma. In multivariable logistic regression analysis, retinal arteriosclerosis showed the strongest association with glaucoma (OR, 6.033; 95% CI, 4.417-8.240; <i>p</i> < 0.001). Older age, male sex, higher intraocular pressure, and higher low-density lipoprotein cholesterol level were also independently associated with glaucoma. A graded relationship was observed between retinal arteriosclerosis severity and glaucoma, with adjusted ORs of 5.51 (95% CI, 3.96-7.66) for grade 1 and 13.15 (95% CI, 6.41-26.99) for grade ≥ 2. <b>Conclusions</b>: In young adults, retinal arteriosclerosis was strongly and dose-dependently associated with glaucoma. These findings suggest that retinal microvascular abnormalities visible on routine fundus photographs may provide clinically accessible information for identifying young adults with structural features of glaucomatous optic neuropathy in health screening settings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traumatic Brain Injury and the Road to Alzheimer's Disease.","authors":"Roxana Kaveh, Farzin Kamari, Poul Flemming Høilund-Carlsen, Morten Blaabjerg, Alex Alban Christensen, Frantz Rom Poulsen, Sarvenaz Ghaedi, Abass Alavi, Sasan Andalib","doi":"10.3390/biomedicines14092056","DOIUrl":"10.3390/biomedicines14092056","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is associated with both mild and moderate to severe traumatic brain injury (TBI). This narrative review gives an account of the association of TBI and AD and highlights possible cellular and molecular pathways linking these pathologies. Following TBI, the immune system of the brain is rapidly activated and gives rise to acute neuroinflammation. While neuroinflammation is protective in nature, it may persist chronically in the case of less-controlled prolonged responses, triggering neuroprotective loss and neurotoxicity. Moreover, reduced clearance of amyloid-beta may occur, along with its overproduction and aggregation. Tau protein regulation is also altered by kinase and phosphatase enzymes, resulting in the accumulation of hyperphosphorylated tau protein in neurons and glial cells and the emergence of intracellular tau neurofibrillary tangles. More to the point, vascular impairment following TBI has been reported to contribute to cognitive decline and AD. Blood-brain barrier breakdown following TBI allows for infiltration of peripheral immune cells and blood-derived proteins into the brain, which exacerbates neuroinflammation, interrupts synaptic signaling, and promotes oxidative stress. The neuroinflammatory response, dynamic alterations in amyloid and tau biology, and vascular impairment are thought to interact within a broader network of processes associated with AD neurodegeneration, rather than acting as isolated mechanisms.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}