Biomedicines最新文献

{"title":"<i>Prg4</i> and Osteoarthritis: Functions, Regulatory Factors, and Treatment Strategies.","authors":"Peng-Jie Fu, Sheng-Yuan Zheng, Yan Luo, Zhuo-Qun Ren, Zi-Han Li, Ya-Ping Wang, Bang-Bao Lu","doi":"10.3390/biomedicines13030693","DOIUrl":"10.3390/biomedicines13030693","url":null,"abstract":"<p><p>Proteoglycan 4 (PRG4), also known as lubricin, plays a critical role in maintaining joint homeostasis by reducing friction between articular cartilage surfaces and preventing cartilage degradation. Its deficiency leads to early-onset osteoarthritis (OA), while overexpression can protect against cartilage degeneration. Beyond its lubricating properties, PRG4 exerts anti-inflammatory effects by interacting with Toll-like receptors, modulating inflammatory responses within the joint. The expression of <i>Prg4</i> is regulated by various factors, including mechanical stimuli, inflammatory cytokines, transcription factors such as Creb5 and FoxO, and signaling pathways like TGF-β, EGFR, and Wnt/β-catenin. Therapeutic strategies targeting <i>PRG4</i> in OA have shown promising results, including recombinant PRG4 protein injections, gene therapies, and small molecules that enhance endogenous <i>Prg4</i> expression or mimic its function. Further research into the molecular mechanisms regulating <i>Prg4</i> expression will be essential in developing more effective OA treatments. Understanding the interplay between <i>Prg4</i> and other signaling pathways could reveal novel therapeutic targets. Additionally, advancements in gene therapy and biomaterials designed to deliver PRG4 in a controlled manner may hold potential for the long-term management of OA, improving patient outcomes and delaying disease progression.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727992","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":"Targeting the PTN/PTPRZ1-ROS Pathway to Promote Bone Regeneration.","authors":"Kai Zhao, Yusi Guo, Ying He, Yujia Wu, Zhewen Hu, Xiaopei Chi, Xuliang Deng","doi":"10.3390/biomedicines13030695","DOIUrl":"10.3390/biomedicines13030695","url":null,"abstract":"<p><p><b>Background</b>: Osteoporosis is a global health problem that significantly decreases patients' quality of life and causes tremendous medical burdens. Therefore, exploring effective targeting strategies for osteoporosis treatment is crucial. Previous studies have indicated that pleiotrophin (PTN) was a secretory factor involved in several biological processes, such as angiogenesis, neural development, and abnormal osteogenic functions in osteoporosis. However, the roles of PTN in osteogenics and the mechanisms remain unclear. <b>Methods</b>: In this study, we explored the effects and mechanisms of PTN in regulating osteogenic functions using real-time quantitative PCR, immunofluorescence, ALP detection, a TUNEL assay, RNA sequencing, and phosphorylation quantitative proteomics. Fracture-healing experiments in osteoporosis rats were also conducted to evaluate the osteogenic functions of PTN in vivo. <b>Results</b>: We found that PTN significantly inhibited apoptosis and promoted the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). Further experiments showed that PTN regulated the biological functions of rBMSCs by promoting antioxidant functions and reducing cellular reactive oxygen species (ROS), thereby protecting rBMSCs from accumulated ROS. Additionally, we found that PTN binds to the PTPRZ1 receptor, inducing intracellular PLCG1 phosphorylation and NCOA3 nuclear translocation, which regulate the downstream antioxidant functions of rBMSCs. Additionally, we verified that PTN effectively promoted fracture healing in osteoporotic animals. <b>Conclusions</b>: This study elucidates the mechanisms by which PTN promotes osteogenesis and verifies this effect in vivo, offering an effective target for osteoporosis treatment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728190","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":"Comparative Efficacy of Subcutaneous Versus Intravenous Interleukin 12/23 Inhibitors for the Remission of Moderate to Severe Crohn's Disease: A Systematic Review and Meta-Analysis.","authors":"Nouran Alwisi, Rana Ismail, Hissa Al-Kuwari, Khalifa H Al-Ansari, Mohammed A Al-Matwi, Noor A Aweer, Wejdan N Al-Marri, Yousif Al-Kubaisi, Muneera Al-Mohannadi, Shahd Hamran, Suhail A R Doi, Habib H Farooqui, Tawanda Chivese","doi":"10.3390/biomedicines13030702","DOIUrl":"10.3390/biomedicines13030702","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Interleukin 12/23 inhibitors are a newer class of monoclonal antibodies used to induce and maintain remission for Crohn's disease (CD), a chronic inflammatory bowel disease, when patients do not respond to conventional immunomodulatory drugs or first-line monoclonal antibody therapies. Although biologics are best administered intravenously, subcutaneous administration has been trialed, with mixed results. This research synthesized evidence on the efficacy and safety of subcutaneous compared to intravenous administration of interleukin 12/23 inhibitors for moderate to severe CD. <b>Methods</b>: In this systematic review and meta-analysis, we searched Cochrane, PubMed, SCOPUS, CINHAL, and preprint archives for randomized controlled trials (RCTs) that compared the efficacy and safety of subcutaneous to intravenous interleukin 12/23 inhibitors for the remission of CD. After study quality assessment, a meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model, heterogeneity was assessed using I², and publication bias was performed using Doi plots. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). <b>Results</b>: Seven RCTs, with 2179 participants, all with moderate to severe CD, were included. After meta-analysis, subcutaneous compared to intravenous administration showed similar efficacy for the induction of remission (OR 0.77, 95%CI 0.53-1.12), with no-to-low heterogeneity (I² = 0%, <i>p</i> = 0.97). For the maintenance of remission, only two studies had analyzable data, and they showed that subcutaneous interleukin 12/23 inhibitors were equal or better compared to intravenous administration. Further syntheses showed that subcutaneous compared to intravenous administration of interleukin 12/23 inhibitors had almost similar odds of adverse events (OR 0.91, 95%CI 0.63-1.32, I² = 39%), serious adverse events (OR 0.97, 95%CI 0.61-1.53, I² = 0%), and treatment discontinuation (OR 1.06, 95%CI 0.67-1.68, I² = 0%). <b>Conclusions</b>: In individuals with moderate to severe CD, subcutaneous administration has similar efficacy for inducing remission with comparable safety. More RCTs are needed to confirm these findings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727990","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 Acute Effects of Varying Frequency and Pulse Width of Transcutaneous Auricular Vagus Nerve Stimulation on Heart Rate Variability in Healthy Adults: A Randomized Crossover Controlled Trial.","authors":"Peter Atanackov, Jakob Peterlin, Maja Derlink, Uroš Kovačič, Nataša Kejžar, Fajko F Bajrović","doi":"10.3390/biomedicines13030700","DOIUrl":"10.3390/biomedicines13030700","url":null,"abstract":"<p><p><b>Background/Objective</b>: Heart rate variability (HRV) is a key biomarker of autonomic function, linked to morbidity and mortality across various diseases. Transcutaneous auricular vagus nerve stimulation (taVNS) shows therapeutic promise, but its effects on HRV and the influence of specific stimulation parameters remain unclear. This study investigated whether the acute effects of taVNS on HRV depend on combinations of stimulation frequency and pulse width. <b>Methods</b>: Seventy-eight healthy adults participated in seven randomized sessions, each testing one of six active taVNS protocols or an inactive sham condition applied to the cymba conchae of the left ear. The active protocols varied by frequency (10 Hz or 25 Hz) and pulse width (100 µs, 250 µs, or 500 µs). The sessions included 15 min of baseline, 15 min of taVNS or sham condition, and 10 min of recovery. HRV was calculated using the standard deviation of NN intervals (SDNN) and the root mean square of successive differences (RMSSD) from continuous ECG recordings. <b>Results</b>: The 10 Hz/250 µs, 10 Hz/500 µs, and 25 Hz/100 µs protocols significantly increased SDNN time series compared to the sham condition. Exploratory analysis revealed SDNN increases during the second 5 min of stimulation with the 10 Hz/500 µs protocol and during the first 5 min of recovery with the 10 Hz/250 µs and 25 Hz/100 µs protocols. No significant changes in the RMSSD were found for any protocol. <b>Conclusions</b>: TaVNS is safe in healthy adults, and specific frequency and pulse width combinations can acutely enhance overall HRV, as reflected in SDNN, but do not affect vagally mediated HRV, as reflected by the RMSSD. Future studies should optimize taVNS parameters to maximize physiological and clinical outcomes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728192","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":"An Assessment of Periodontal Status and Oral Hygiene in Patients with Hypertension in the South-West Region of Romania.","authors":"Ana Pavalan, Allma Roxana Pitru, Dorin-Nicolae Gheorghe, Cristina Florescu, Dora Maria Popescu, Ana Maria Rîcă, Flavia Nicolae, Adina Andreea Turcu, Petra Surlin","doi":"10.3390/biomedicines13030696","DOIUrl":"10.3390/biomedicines13030696","url":null,"abstract":"<p><p><b>Background:</b> This cross-sectional analytical study evaluates oral hygiene and periodontal status in patients with hypertension, given the established link between cardiovascular diseases and poor periodontal health. <b>Methods:</b> A total of 24 hypertensive patients (15 male; 9 female) and 30 healthy controls (19 male; 11 female) from Craiova, Romania, were assessed using Periodontal Probing Depth (PPD), the Plaque Index (PLQ), and the Bleeding on Probing Index (BPI). <b>Results:</b> The mean age was 62.2 years in the hypertensive group and 47.4 years in the control group. Oral hygiene was poorer in hypertensive patients (PLQ: 73% vs. 24.1% in controls), with higher PPD (5.2 mm vs. 3.7 mm) and BPI (82% vs. 23%). Among patients with dental implants, PLQ was 24% in hypertensive individuals vs. 15.6% in controls, PPD was 4.4 mm vs. 2.9 mm, and BPI was 44% vs. 15.5%. <b>Conclusions:</b> These findings indicate a higher risk of periodontal disease in hypertensive patients, though dental implants may decrease some adverse effects by improving oral hygiene and periodontal health in this population. In conclusion, our study highlights that patients with high blood pressure have a less favorable periodontal status compared to healthy controls.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728073","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":"Association of Monoamine Oxidase A Gene Promoter Region (30 bp μVNTR) Polymorphism with Serum Levels in Multiple Psychiatric Disorders.","authors":"Aisha Nasir Hashmi, Rizwan Taj, Zehra Agha, Raheel Qamar, Jamal B Williams, Maleeha Azam","doi":"10.3390/biomedicines13030698","DOIUrl":"10.3390/biomedicines13030698","url":null,"abstract":"<p><p><b>Background:</b> Monoamine oxidase A (MAOA) has a role in metabolising different biogenic amines, including dopamine. Functional studies have revealed the effect of promoter region variants on the transcriptional activity of the <i>MAOA</i> that consequently affects the homeostasis of the biogenic amines which might implicate in the aetiology of multiple psychiatric conditions. <b>Objectives:</b> The current study aimed to determine the influence of the promoter region 30 base pair (bp), a variable number of tandem repeats (VNTR) of the <i>MAOA</i>, on its serum levels and association with schizophrenia (SHZ), bipolar disorder (BD), and major depressive disorder (MDD) in the Pakistani population. <b>Methods:</b> A total of 1062 subjects [MDD <i>n</i> = 416, BD <i>n</i> = 200, SHZ <i>n</i> = 97 and controls <i>n</i> = 349], were genotyped for <i>MAOA</i>-30bp µVNTR through standard polymerase chain reaction technique and logistic regression was applied to determine the genetic association. Serum MAOA levels were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann-Whitney U test was applied. <b>Results:</b> In genotype analysis, eight different repeat (R) alleles of <i>MAOA</i>-30 bp µVNTR were observed, where 4.5R, 5.5R, and 6R were the rare repeats found in the current Pakistani cohort. In serum-based analysis the total MAOA serum levels were found to be significantly elevated in SHZ; however, in sub-group analysis, significantly higher serum levels of MAOA were observed only in the rare allele groups of MDD, BD, and SHZ. <b>Conclusions:</b> The current study gives us further insights into the complex nature of <i>MAOA</i> regulation and its genetic and serum-levels association with different psychiatric conditions.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727822","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":"Determination of Cortisol Levels in a Small Volume of Saliva of COVID-19-Recovering Patients During Treatment with Psychotropic Drugs.","authors":"Ewelina Dziurkowska, Grażyna Guz-Rzeniecka, Maciej Dziurkowski","doi":"10.3390/biomedicines13030697","DOIUrl":"10.3390/biomedicines13030697","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Cortisol levels are increased in stressful situations but can also result from a history of COVID-19 infection. Long-term exposure to high cortisol levels has a destructive effect on the CNS (Central Nervous System) and can lead to depression, among other things. The most commonly used psychotropic drugs reduce cortisol concentrations. <b>Methods:</b> The aim of our study was to develop an analytical method to determine the level of the hormone in a small volume of saliva (200 µL) in COVID-19 patients using CNS-active drugs. Solid-phase extraction was used to isolate the analyte, and the determination was performed by liquid chromatography with a diode array detector (LC with DAD). <b>Results</b>: The developed method was validated. Its linearity was determined to be in the range of 4-500 ng/mL (R² > 0.9986) and the intra- and inter-day precision expressed as coefficient of variation (CV%) did not exceed 12%. The method was then applied to determine cortisol levels in the saliva of post-COVID-19-recovered patients and healthy volunteers. The determined cortisol levels were 12.24 ± 7.33 ng/mL in the recovered patients and 4.11 ± 1.46 ng/mL in the healthy subjects, respectively. A comparison of the results showed that cortisol levels in the recovered patients and healthy volunteers were significantly different statistically. <b>Conclusions</b>: The developed method allowed for the determination of cortisol in a small volume of saliva. Comparison of cortisol concentration in healthy individuals and COVID-19 recoveries indicates that the hormone level in both groups significantly differed statistically, and the psychotropic drugs used did not reduce cortisol concentration in COVID-19 patients. The results obtained indicate that the psychotropic drugs used did not reduce cortisol concentrations in COVID-19 patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728123","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":"Obesity, but Not Overweight, Is Associated with Increased Presepsin Levels in Infection-Free Individuals: An Exploratory Study.","authors":"Theocharis Koufakis, Dimitrios Kouroupis, Georgios Dimakopoulos, Theofylaktos Georgiadis, Areti Kourti, Panagiotis Doukelis, Ioanna Zografou, Dimitrios Patoulias, Djordje S Popovic, Athina Pyrpasopoulou, Luca Busetto, Alexander Kokkinos, Vasilios Tsimihodimos, Kalliopi Kotsa, Michael Doumas, Kali Makedou","doi":"10.3390/biomedicines13030701","DOIUrl":"10.3390/biomedicines13030701","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Intestinal dysbiosis and systemic inflammation are involved in the pathophysiology of obesity and its complications. Presepsin is a recently discovered inflammation marker, being the soluble form of the bacterial lipopolysaccharide (LPS) receptor. Due to the imbalance of the gut flora and subsequent disruption of the intestinal barrier, circulating LPS levels have been found to be elevated in patients with metabolic diseases, even in the absence of infection. However, to date, no studies have evaluated whether obesity is associated with elevated presepsin levels. <b>Methods</b>: The present study included 81 participants (61.7% women, 27 with obesity, 34 with overweight, and 20 controls with normal body mass index), all free of infection and diabetes mellitus. Presepsin was measured in serum by ELISA, and its concentrations were compared between the groups. <b>Results</b>: The obesity group had higher presepsin levels compared to controls (8.09 vs. 4.45 ng/mL, <i>p</i> = 0.06). When participants with a history of cardiovascular disease were excluded from the analysis and adjusting for multiple confounders through a regression model, the obesity group had higher presepsin values than the overweight and control groups (5.84 vs. 3.32 ng/mL, <i>p</i> = 0.016). In contrast, the overweight group had lower concentrations than both the obesity group (<i>p</i> = 0.005) and the controls (<i>p</i> = 0.031). We did not find an association between presepsin and 25-hydroxy vitamin D levels (<i>p</i> = 0.368). <b>Conclusions</b>: Although the cross-sectional character of the study cannot demonstrate causal relationships, the results could potentially suggest that systemic inflammation is implicated in the pathogenesis of obesity through the disruption of the intestinal barrier. However, the findings should only be seen as hypothesis-generating. The reduction in presepsin in the overweight state is an interesting finding that deserves further investigation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727879","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 Immune Environment in Colorectal Adenoma: A Systematic Review.","authors":"Ugne Silinskaite, Jurate Valciukiene, Matas Jakubauskas, Tomas Poskus","doi":"10.3390/biomedicines13030699","DOIUrl":"10.3390/biomedicines13030699","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Research on colorectal adenoma is significantly less comprehensive compared to studies on colorectal carcinoma. Although colorectal adenoma is a precursor of the majority of sporadic colorectal cancers, not all adenomas develop into carcinomas. The complex interaction of immune responses in the premalignant tumor microenvironment might be a factor for that. <b>Methods:</b> In this systematic review, we aim to provide a thorough analysis of the current research examining the immune infiltration patterns in sporadic colorectal adenoma tissues in the context of immune cell-based, cytokine-based, and other immunological factor-related changes along the conventional adenoma-carcinoma sequence. The articles included in the review extend up to December 2024 in PubMed and Web of Science databases. <b>Results:</b> Most included studies have shown significant differences in immune cell counts, densities, and cytokine expression levels associated with premalignant colorectal lesions (and/or colorectal cancer). No consensus on the immune-related tendencies concerning CD4+T cells and CD8+T cells was reached. Decreasing expression of mDCs and plasma and naïve B cells were detected along the ACS. The increased density of tissue eosinophils in the adenoma tissue dramatically diminishes after the transition to carcinoma. As the adenoma progresses, the increasing expression of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, IL-23, IL-33, and TGF-β and decreasing levels of IL-12A, IL-18, IFN-γ, and TNFα cytokines in the invasive carcinoma stage is being detected. The over-expression of COX-2, PD-1/PD-L1, CTLA-4, and ICOS/ICOSLG in the colorectal adenomatous and cancerous tissues was also observed. <b>Conclusions:</b> Further studies are needed for a better understanding of the whole picture of colorectal adenoma-associated immunity and its impact on precancerous lesion's potential to progress.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728204","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":"Neutrophil Heterogeneity in Wound Healing.","authors":"Filippo Renò, Corinna Anais Pagano, Monica Bignotto, Maurizio Sabbatini","doi":"10.3390/biomedicines13030694","DOIUrl":"10.3390/biomedicines13030694","url":null,"abstract":"<p><p>Neutrophils are the most abundant type of immune cells and also the most underestimated cell defenders in the human body. In fact, their lifespan has also been extensively revised in recent years, going from a half-life of 8-10 h to a longer lifespan of up to 5.4 days in humans; it has been discovered that their mechanisms of defense are multiple and finely modulated, and it has been suggested that the heterogeneity of neutrophils occurs as well as in other immune cells. Neutrophils also play a critical role in the wound healing process, and their involvement is not limited to the initial stages of defense against pathogens, but extends to the inflammatory phase of tissue reconstruction. Neutrophil heterogeneity has recently been reported at the presence of distinct subtypes expressing different functional states, which contribute uniquely to the different phases of innate immunity and wound healing. This heterogeneity can be induced by the local microenvironment, by the presence of specific cytokines and by the type of injury. The different functional states of neutrophils enable a finely tuned response to injury and stress, which is essential for effective healing. Understanding the functional heterogeneity of neutrophils in wound healing can unveil potential pathological profiles and therapeutic targets. Moreover, the understanding of neutrophil heterogeneity dynamics could help in designing strategies to manage excessive inflammation or impaired healing processes. This review highlights the complexity of neutrophil heterogeneity and its critical roles throughout the phases of wound healing.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727869","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}