International Journal of Molecular Sciences最新文献

{"title":"Improving Grain Shape of the Rice Variety Exiangsimiao by Introgressing the Long-Grain Allele of <i>GL7</i>/<i>GW7</i>.","authors":"Hui Hu, Zhilian Qi, Zheqin Wang, Nannan Liu, Junying Xu, Haiyang Liu, Longwei Yang, Jiefeng Jiang, Famao Liang, Xianjin Qiu","doi":"10.3390/ijms27198930","DOIUrl":"10.3390/ijms27198930","url":null,"abstract":"<p><p>Exiangsimiao (EXSM) is a high-yield and high-quality <i>indica</i> variety and restorer line. However, its grains are not sufficiently slender. In this study, the long-grain allele of the grain shape gene <i>GL7</i>/<i>GW7</i> was introgressed into EXSM via marker-assisted selection combined with backcross breeding, and two improved long-grain lines (EXSM-IL1 and EXSM-IL2) were developed. Their background recovery rates reached 96.70% and 97.50%, respectively. Their grain lengths (GLs) and length-to-width ratios (LWRs) were significantly higher than EXSM. The milling quality, especially the head milled rice rate (HMRR), of both improved lines was significantly lower than EXSM. EXSM-IL1 showed no significant difference in grain yield (GY) to EXSM, although both improved lines had shorter total growth duration (TGD), longer panicle length (PL), and a lower seed setting ratio (SSR) and 1000-grain weight (KGW). Six hybrid combinations derived from the improved lines exhibited longer GL, higher LWR and narrower GW than those of the hybrid combinations derived from EXSM. The TGD and KGW of the six hybrid combinations were significantly lower compared with the hybrids from EXSM. Furthermore, the two improved lines carried 41 favorable genes associated with crucial traits. These results provide the basis for rice grain shape improvement and supply long-grain and high-quality breeding lines and restorer lines for rice production in southern China.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative Serum Transient Receptor Potential Ankyrin 1 (TRPA1) Levels in Class III Obesity: A Prospective Controlled Observational Study.","authors":"Nizamettin Kutluer, Onur Ağ, Tamer Gündoğdu, Mehmet Zeki Öğüt, Denizhan Kılıç, Hakan Ayyıldız, Serhat Doğan, Mehmet Buğra Bozan","doi":"10.3390/ijms27198919","DOIUrl":"10.3390/ijms27198919","url":null,"abstract":"<p><p>Transient Receptor Potential Ankyrin 1 (TRPA1) is a membrane cation channel activated by oxidative stress products that are chronically elevated in class III obesity. Although tissue-level TRPA1 biology is increasingly well described, the biological meaning of circulating immunoreactive TRPA1 remains poorly established. This single-centre, prospective, controlled observational study compared preoperative serum TRPA1 between adults with class III obesity scheduled for laparoscopic sleeve gastrectomy and contemporaneous controls, and explored metabolic and inflammatory correlates of the circulating signal. Serum TRPA1 was quantified by enzyme-linked immunosorbent assay (ELISA) in 42 consecutive surgical candidates and 36 controls. The primary analysis used continuous (log-transformed) TRPA1 with age- and sex-adjusted logistic regression; ROC-derived dichotomisation was retained only as an exploratory analysis. Serum TRPA1 did not differ between groups (median 309.8 vs. 340.5 pg/mL; Mann-Whitney U, <i>p</i> = 0.323; Hodges-Lehmann median difference [obesity - control] -30.8 pg/mL, bootstrap 95% CI -227.43 to 43.02). After adjustment for age and sex, continuous log-TRPA1 was not independently associated with obesity status (OR per log-unit 0.88, 95% CI 0.46-1.69; <i>p</i> = 0.699), and discrimination was poor (AUC 0.435; 95% CI 0.305-0.562). Established inflammatory and metabolic markers differed between groups, but serum TRPA1 did not track them. In this cohort, preoperative serum TRPA1 did not distinguish class III obesity from controls. The negative circulating finding should be interpreted as lack of evidence for a large between-group difference in ELISA-measured serum TRPA1-and as a potential translational disconnect from tissue TRPA1 biology-rather than as the definitive exclusion of any tissue-level role for the channel.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure, Evolution and Functional Inference on the CDP Gene Family in European Hazelnut.","authors":"Ciro Gianmaria Amoroso, Barbara Auzino, Adriana Rita Evangelista, Rosa Pilolli, Chiara Nitride, Giuseppe Andolfo","doi":"10.3390/ijms27198924","DOIUrl":"10.3390/ijms27198924","url":null,"abstract":"<p><p>Food allergy is an IgE-mediated response of the immune system of sensitive subjects to specific proteins. The recent WHO/FAO consultation included hazelnut (<i>Corylus avellana</i> L.) in the list of global priority allergenic ingredients. One of the most common hazelnut allergen groups encompasses the Cupin_1 domain-containing proteins (CDPs). To date, three CDP allergens (<i>Cor a 9</i>, <i>Cor a 11</i>, and <i>Cor a 16</i>) have been deposited into the official WHO/IUIS database. Recently, using a whole-genome approach, the <i>Cor a</i> loci were mapped in four <i>Corylus</i> species. However, the task of identifying novel CDP allergen candidates directly within the genome has not yet been addressed. The recently available <i>C. avellana</i> cv. 'Tombul' genome sequence allowed the identification of 114 hazelnut CDP-encoding genes. The maximum likelihood analysis allowed us to reconstruct the evolutionary relationships underlying the diversification and expansion of the CDP superfamily. Several duplication events associated with lineage-specific evolution were discovered. Interestingly, conserved epitopes and amino acid motifs that likely play a role in allergenic function were also identified. A total of 42 cis-acting regulatory elements were shared in the promoter regions of known and new putative allergens. Using the well-known CDP allergens as an internal benchmark, we have identified and molecularly analyzed new CDP allergen candidates. To provide a first transcriptional characterization, <i>Cor a 9</i>, <i>Cor a 11</i>, and <i>Cor a 16</i> were analyzed by real-time PCR. The expression analysis showed generally low relative transcript levels of Cor a genes in immature reproductive tissues compared with young leaves. Interestingly, mass spectrometry analysis confirmed the accumulation of known allergens and several predicted CDP allergen candidates in commercial hazelnut flour. The data reported here may help to further address food safety questions and could be conveniently used in breeding research aimed at developing hypoallergenic cultivars.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sugar-Specific Modulation of Trophoblast Function and Bioenergetics Under Metabolic Stress Conditions.","authors":"Elizabeth Thurmond, Madeline Boyer, Benjamin T Bikman, Paul R Reynolds, Juan A Arroyo","doi":"10.3390/ijms27198920","DOIUrl":"10.3390/ijms27198920","url":null,"abstract":"<p><p>How sugars other than glucose affect trophoblast function is poorly understood, particularly under the metabolic stress of diabetic pregnancy. We compared glucose, fructose, and the minimally metabolized sugar allulose in two trophoblast cell lines, SW71 (first-trimester, extravillous-like) and BeWo (choriocarcinoma-derived, villous). Each sugar was added at 25 mM for 24 h to the cells' standard glucose-containing media (11 mM, SW71; 17.5 mM, BeWo) to model metabolic stress. All three sugars increased the number of cells recovered (2.4- to 6.5-fold in SW71; ~10- to 15-fold in BeWo) and reduced viability (~9-75%), with fructose causing the largest loss in both lines. Intracellular reactive oxygen species increased 5.2- to 7.8-fold with all sugars. Oxygen consumption differed by sugar: in SW71 cells, glucose and allulose increased ADP-stimulated and succinate-supported respiration, whereas fructose reduced it, and in BeWo cells only fructose increased it. SW71 invasion was ~7-fold higher after allulose than after glucose or fructose. BeWo cells were studied undifferentiated, so effects on syncytialization were not assessed. The three sugars are therefore not interchangeable in their effects on trophoblast cells in vitro. Because the concentrations exceed those in maternal blood, these findings are hypothesis-generating and require testing at physiological concentrations and in primary trophoblast models.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Biomarkers Linking Psoriasis and Cardiovascular Disease: Current Evidence and Clinical Perspectives.","authors":"Mateusz Matwiejuk, Hanna Myśliwiec, Agnieszka Mikłosz, Oksana Jarocewicz, Adrian Chabowski, Iwona Flisiak","doi":"10.3390/ijms27198918","DOIUrl":"10.3390/ijms27198918","url":null,"abstract":"<p><p>Psoriasis is a chronic, immune-mediated inflammatory disease affecting the skin, nails, and joints. Its complex pathogenesis results from interactions between genetic susceptibility and environmental factors and is accompanied by an increased risk of multiple systemic comorbidities, particularly cardiovascular disease. Growing evidence indicates that both conditions share common molecular pathways driven by chronic inflammation, endothelial dysfunction, metabolic disturbances, and immune dysregulation. Among the emerging molecular biomarkers, chemerin, endocan, and growth differentiation factor-15 (GDF-15) have attracted considerable attention due to their role in vascular homeostasis, adipose tissue biology, glucose metabolism, and inflammatory signaling. This review summarizes current evidence on the involvement of these biomarkers in psoriasis and cardiovascular disease, highlighting their contribution to the molecular mechanisms underlying the psoriasis-cardiovascular disease axis. Furthermore, we discussed their potential usefulness as candidate biomarkers for cardiovascular risk. However, prospective validation is strictly required to confirm their clinical utility and establish their incremental predictive value beyond conventional risk factors.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production, Optimization and Characterization of Biobased Itaconic Acid from <i>Saccharomyces cerevisiae</i>.","authors":"Zulfiye Velioglu Tosuner, Mehdi Kosaca, Raziye Ozturk Urek, Onur Yilmaz, Catalina Natalia Yilmaz","doi":"10.3390/ijms27198923","DOIUrl":"10.3390/ijms27198923","url":null,"abstract":"<p><p>Itaconic acid (IA) is an important bio-based platform chemical with applications in the production of polymers, coatings, resins, and other value-added materials. However, its conventional microbial production relies predominantly on microorganisms that present safety and process-related limitations. This study investigated <i>Saccharomyces cerevisiae</i> BY4742 as a potentially safer microbial platform for the production of bio-based IA under submerged fermentation conditions. IA production was optimized using response surface methodology with a Box-Behnken design, considering glucose concentration, initial pH, and CaCI₂ concentration as independent variables. The maximum IA concentration of 1133.50 ± 54.92 mg/L was obtained at 30 °C, pH 4.5, with 10% (<i>w</i>/<i>v</i>) glucose and without CaCI₂ supplementation after 216 h of fermentation. The fermentation-derived IA was subsequently recovered and characterized using high-performance liquid chromatography, Fourier-transform infrared spectroscopy, ¹H-nuclear magnetic resonance (¹H-NMR), and thermogravimetric analysis. The analytical results confirmed the molecular identity and high chromatographic purity of the recovered IA. Furthermore, the homopolymerization ability of the fermentation-derived IA was evaluated and compared with that of commercial IA under the same reaction conditions. The ¹H-NMR results demonstrated changes consistent with consumption of the IA C=C double bond following polymerization, indicating that the fermentation-derived IA retained its ability to undergo homopolymerization. Overall, these findings demonstrate the potential of <i>S. cerevisiae</i> for producing structurally confirmed bio-based IA and provide a proof of concept for its use as a renewable monomer for poly(itaconic acid) synthesis, supporting its further investigation for the development of bio-based polymeric materials.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible Links Between PM_2.5-Induced NLRP3 Inflammasome Activation and Its Role in Lung Cancer Progression and Drug Resistance.","authors":"Thanaphat Worawichitchaikun, Pitchapa Wantanachaisaeng, Teerapat Teeppaibul, Prasit Suwannalert","doi":"10.3390/ijms27198931","DOIUrl":"10.3390/ijms27198931","url":null,"abstract":"<p><p>The rising incidence of lung cancer is increasingly linked to fine particulate matter (PM_2.5) exposure, highlighting its role as a risk factor of lung carcinogenesis. However, the molecular mechanisms behind PM_2.5 and the disease remain incompletely understood. Exposure to PM_2.5 triggers inflammatory processes, primarily via ROS overproduction, which activates the NLRP3 inflammasome, a cytosolic NOD-like pattern recognition receptor protein complex that cleaves caspase-1 and drives maturation of pro-interleukin-1β (IL-1β) and pro-interleukin-18 (IL-18), leading to chronic pulmonary inflammation. Based on current evidence, this review displays PM_2.5-induced ROS upregulation as an essential trigger of NLRP3 inflammasome activation in lung cancer development and progression and hypothesises that the signalling of NLRP3 may contribute to molecular pathways associated with lung cancer drug resistance. There have been uses of NLRP3 inhibitors in clinical trials of different inflammatory diseases, but none has yet reached clinical testing in oncology. We propose the potential of NLRP3 as a possible prognostic marker and a therapeutic target for PM_2.5-associated lung cancer drug resistance.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted Metabolomics Reveals Regional and Cultivar-Associated Metabolomic Variation in Soybeans Across Northeast China.","authors":"Jinghui Wang, Lupeng Gou, Haohai You, Feng Wang, Jie Zhu, Yinqi Wang, Zijian Xia, Zhuoduojie Kuan, Zhaohui Wang","doi":"10.3390/ijms27198925","DOIUrl":"10.3390/ijms27198925","url":null,"abstract":"<p><p>Soybean (Glycine max) quality and metabolic composition are shaped by complex interactions between genetic background and agro-ecological conditions, making metabolic characterization across major production regions valuable for germplasm evaluation and quality-oriented breeding. In this study, an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach was applied to compare the mature seed metabolomes of nine representative commercial soybean cultivars sampled from two major production regions in Northeast China: Heilongjiang (HLJ, four cultivars from Harbin) and Liaoning (LN, five cultivars from Shenyang). Because region-specific cultivars were collected from a single site and seed lot per province without direct site-level meteorological or soil measurements, genotype and environment are confounded in this observational design, and the observed differences reflect the combined variation in the sampled cultivar-location cohorts. After preprocessing, 8283 features were putatively annotated (MSI Level 2/3). Multivariate statistical analyses (PCA, PLS-DA, and OPLS-DA) combined with cultivar-grouped cross-validation revealed clear metabolic separation between the sampled HLJ and LN cohorts. A total of 1485 putatively annotated metabolites (VIP > 1.0, subsample-level FDR < 0.05, fold change HLJ/LN > 2.0 or <0.5) were screened as exploratory candidate differential metabolites, with 953 exhibiting higher abundance (FC>2.0) and 532 exhibiting lower abundance (FC<0.5, i.e., higher abundance in LN) in HLJ soybeans relative to LN soybeans. Exploratory KEGG pathway mapping (based on nominal p-values, as no pathway reached FDR-adjusted q<0.05) indicated nominal enrichment in isoflavonoid biosynthesis (p=0.0043, q=0.261) and tryptophan metabolism (p=0.0093, q=0.283); specifically, sampled LN cultivar-location combinations exhibited higher steady-state abundances of isoflavones and their glycosylated derivatives, whereas sampled HLJ soybeans exhibited higher steady-state abundances of specific lipid species (unsaturated fatty acyls, sphingolipids) and tryptophan-derived indoleamines. In the absence of direct environmental measurements, potential links between these steady-state metabolic signatures and regional macroclimatic differences (such as thermal regimes or high-latitude cold stress) are proposed strictly as exploratory, literature-informed hypotheses. Overall, these findings provide preliminary candidate metabolic markers for characterizing the sampled regional soybean germplasm; however, independent validation across additional harvest years, multiple geographic sites, independent seed lots, and broader cultivar panels will be required before these candidate metabolites can be considered validated biomarkers for geographic authentication.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis Susceptibility in Pediatric Immune Thrombocytopenia: Alteration in Mesenchymal Stromal Cells.","authors":"Giuseppe Di Feo, Maria Maddalena Marrapodi, Oriana Di Domenico, Lucia Argenziano, Michele La Manna, Elisabetta Lembo, Giuseppe Palumbo, Francesca Rossi, Alessandra Di Paola","doi":"10.3390/ijms27198917","DOIUrl":"10.3390/ijms27198917","url":null,"abstract":"<p><p>Immune thrombocytopenia (ITP) is the most common pediatric thrombocytopenia, characterized by immune-mediated platelet destruction and altered inflammatory responses. Among these alterations, mesenchymal stromal cells (MSCs) from ITP patients display reduced viability and impaired immunoregulatory functions. Our previous work revealed dysregulated iron metabolism in ITP-MSCs, with increased intracellular iron accumulation driven by hepcidin-FPN1 axis disruption and overexpression of iron importers. Given the link between iron overload, oxidative stress, and ferroptosis, a regulated iron-dependent form of cell death, we investigated whether ITP-MSCs exhibit oxidative and molecular alterations associated with ferroptosis. ITP-MSCs showed increased ROS levels and ACSL4 expression, together with reduced expression of proteins involved in ferroptosis-related antioxidant defense, including SLC3A2, SLC7A11, and GPX4. Increased extracellular release of HMGB1, a DAMP associated with cellular stress and different forms of regulated cell death, was also observed. Treatment with Ferrostatin-1 (Fer-1) and Deferasirox (DFX) reduced oxidative stress and partially restored the expression of ferroptosis-related markers. Similarly, high-dose dexamethasone (HD-Dexa) reduced ROS and ACSL4 levels and limited extracellular HMGB1 release. Collectively, these findings support increased susceptibility to ferroptotic stress in ITP-MSCs and reveal a ferroptosis-associated oxidative stress phenotype with concomitant alterations in ferroptosis-related molecular pathways. Moreover, the effects of HD-Dexa, DFX, and Fer-1 suggest that modulation of these pathways may represent a potential strategy for limiting oxidative cellular damage in ITP-MSCs.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraosseous Lidocaine Trigger Point Injection for Vertebrogenic Pain: From Molecular Principles to Clinical Applications: A Narrative Review.","authors":"Mustafa Al-Zamil, Natalia A Shnayder, Marina M Petrova, Margarita V Naprienko, Ivan V Zhelambekov, Olga V Goncharova, Natalia P Garganeeva, Svetlana V Kuleshova, Oxana V Eremina, Anna O Dobrosmyslova","doi":"10.3390/ijms27198935","DOIUrl":"10.3390/ijms27198935","url":null,"abstract":"<p><p>Intraosseous lidocaine trigger point injection (LTPI) has been utilized for an extended period in the management of chronic vertebrogenic pain; yet, its molecular mechanisms and clinical efficacy require critical appraisal. This narrative review highlights the milestones of osteoreception and elucidates the molecular mechanisms driving intraosseous receptor irritation and its pivotal role in chronic pain development. Pathological vertebral bone remodeling triggers a receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) imbalance, accelerating hyperactive osteoclastogenesis. Enhanced osteoclastic vacuolar-type H+-ATPase (V-ATPase) expression drives microenvironment acidity and intraosseous hypertension, persistently stimulating acid-sensing ion channel 3 (ASIC3) and purinergic P2X2/3 receptors on intraosseous afferents. Concurrently, upregulated nerve growth factor (NGF) binds to tropomyosin receptor kinase A (TrkA), driving peripheral sensitization via transient receptor potential vanilloid 1 (TRPV1) phosphorylation. The available clinical studies investigating intraosseous LTPI for vertebrogenic pain are scarce and heterogeneous, focusing primarily on low back pain, cervicalgia, and residual chronic pain after degenerative lumbar spinal stenosis decompression surgery. The reviewed data provide preliminary signals of potential benefit, observing a statistically significant analgesic effect of intraosseous LTPI within the studied cohorts. In two trials comparing it to intramuscular LTPI, one of which utilized a randomized controlled design, the intraosseous approach was reported to provide more pronounced short-term pain relief. However, these trials are limited by small sample sizes, heterogeneous designs, and a lack of active long-term safety monitoring. Nevertheless, although current data provide promising but still limited insights, future double-blinded, multicenter randomized controlled trials are required to comprehensively establish the clinical efficacy, safety profile, and prolonged effect of intraosseous LTPI in the treatment of vertebrogenic pain.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}