Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
A Commemorative Special Issue in Honor of Prof. Giovanni De...
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 20420

Special Issue Editors

Prof. Dr. Consolato M. Sergi

E-Mail Website
Guest Editor
1. Division of Anatomic Pathology, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada
2. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
Interests: gastrointestinal/biliary diseases; metabolic diseases; congenital heart disease; mitochondrial DNA-related cardiomyopathies; carcinogenesis (bone/liver)
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Angelo Ravelli

E-Mail Website
Guest Editor
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal-Infantile Sciences (DiNOGMI), University of Genoa, Genoa, Italy
Interests: childhood rheumatic diseases; lupus nephritis; autoantibodies
Dr. Luca Pio

E-Mail Website
Guest Editor
Department of Surgery, St. Jude Children’s Research Hospital, MS 133, 262 Danny Thomas Place, Memphis, TN 38105, USA
Interests: pediatric surgical oncology; neuroblastoma; robotic surgery; translational surgery; precision surgery; image-guided surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Living in Liguria, gathering that the sea may be a metaphor for the human condition is not difficult. The Nobel Prize winner for literature (1975), Eugenio Montale, was born in Genoa in 1896 and spent his childhood and youth between his hometown and the picturesque village of Monterosso, in Cinque Terre. Paraphrasing Mengaldo here, the ego feels almost pulled in by the sea, and simultaneously, it is ejected and confined to the land-dwelling. Montale’s collection “Ossi di Seppia” is an evocation and allegory of the misery and marginalization of the human condition, which moved Giovanni De Toni into action.

Two years before Montale won his Nobel Prize for literature, Giovanni de Toni, an outstanding pediatrician and director of one of the largest children’s hospitals worldwide, passed away. Born in Venice in 1895, Giovanni De Toni was an Italian pediatrician. Known internationally for describing the so-called De Toni–Fanconi–Debré syndrome, he was a prominent figure in Italy, so much so that the Department of Pediatric Sciences of the University of Genoa bears his name. With his wife, Prof. Dr. De Toni also launched the “Villa Santa Chiara” in Genoa to assist disabled children. In 1933, he described a new type of pathology later known as “De Toni–Fanconi–Debré syndrome”. The disease established a cornerstone in vitamin D-resistant rickets. Later, he characterized children affected by hyperosteogenesis and was an authentic innovator in auxologic studies. According to many scholars, De Toni identified a form of infantile cortical hyperostosis, also studied in 1945 by John Caffey and William Silverman (the so-called “Caffey–De Toni disease”). In 1942, Prof. De Toni assumed the director position at the Istituto Gaslini, where he creatively transformed the approach to pediatric healthcare by instituting a free outpatient clinic within the hospital. His prominence rose during the tuberculosis epidemic, as he was the forerunner in detecting a cure with streptomycin. In the 1950s, Giovanni De Toni was remembered as a fervent breastfeeding supporter. On 1 November 1965, the pediatrician left his role at the pediatric institution. He subsequently became president of the Italian Society of Pediatrics (SIP), a position he held from 1966 to the time of his death in Genoa on 8 January 1973. This Special Issue is dedicated to his legacy at the Gaslini Children’s Hospital and to his descendants, Ettore and Teresa, who followed in his footsteps on the scientific journey.

Prof. Dr. Consolato M. Sergi
Prof. Dr. Angelo Ravelli
Dr. Luca Pio
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bone
  • soft tissue sarcomas
  • neuroblastoma

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (15 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

24 pages, 8438 KiB  
Article
Neutrophils in the Spotlight—An Analysis of Neutrophil Function and Phenotype in ARDS
by Richard F. Kraus, Lisa Ott, Kirsten Utpatel, Martin G. Kees, Michael A. Gruber and Diane Bitzinger
Int. J. Mol. Sci. 2024, 25(23), 12547; https://doi.org/10.3390/ijms252312547 - 22 Nov 2024
Abstract
Acute respiratory distress syndrome (ARDS) is a complex disease pattern in which pathogenesis polymorphonuclear neutrophil granulocytes (PMN) play a key role. In previous experiments, we could show that interaction with collagen III (an important component of pulmonary tissue) is a possible trigger of [...] Read more.
Acute respiratory distress syndrome (ARDS) is a complex disease pattern in which pathogenesis polymorphonuclear neutrophil granulocytes (PMN) play a key role. In previous experiments, we could show that interaction with collagen III (an important component of pulmonary tissue) is a possible trigger of neutrophil reactive oxygen species (ROS) production. To investigate possible correlations, further elucidate ARDS pathophysiology, and maybe find pharmacological targets, we evaluated PMNs from blood (circulating PMNs: cPMNs) and tracheal secretion (tPMNs) from patients with and without ARDS with regard to function and phenotype. Blood samples and tracheal secretions were obtained from intensive care patients with and without ARDS. Isolation of cPMN was performed by density-gradient gravity sedimentation without centrifugation. For tPMN isolation, endotracheal aspirate was filtered, and tPMNs were separated from the remaining aspirate using a particle filter. Specific surface epitopes (CD66b, CD62L, fMLP-receptor, LOX-1, CD49d, CD29, CD11b) of the isolated PMN cells were labeled with antibody-coupled dyes and analyzed by flow cytometry. Neutrophil ROS production before and after activation with N-formyl-methyl-leucyl-phenylalanine (fMLP) and tumor necrosis factor α (TNFα) was quantified using rhodamine-123. In addition, a qualitative cytological hematoxylin-eosin (HE) staining was performed with a portion of the secretion. tPMNs were observed in both bloody and mucosal tracheal secretions from ARDS patients. The epitope distribution on cPMNs and tPMNs differed significantly in patients with and without ARDS: tPMNs generally showed increased expression of CD66b, LOX-1 and fMLP-receptor compared to cPMNs, and decreased expression of CD62L. The CD49d levels of all cPMNs were at the same level as tPMNs in ARDS, whereas CD49d expression was increased on tPMNs without ARDS. ROS production was significantly stimulated by fMLP/TNFα in cPMNs regardless of the patient group, while it was similarly increased in tPMNs with and without stimulation. Increased expression of CD66b, LOX-1 and fMLP-receptor on tPMNs indicated a higher activity status compared to cPMNs. Increased CD49d expression on tPMNs without ARDS marks different PMN surface changes in lung disease. PMNs appear to be in a more activated state in lung secretions than in blood, as indicated by higher CD66b and lower CD62L expression, higher constitutive ROS production and lower excitability with fMLP and TNFα. In the context of possible CD49d-triggered ROS production, it is noteworthy that CD49d is downregulated in secretion from patients with ARDS compared to patients without. This phenotypic and functional PMN characterization can provide valuable diagnostic and therapeutic information for the intensive care treatment of ARDS patients. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

15 pages, 3934 KiB  
Article
A Tumor Homing Peptide-Linked Arsenic Compound Inhibits Pancreatic Cancer Growth and Enhances the Inhibitory Effect of Gemcitabine
by Hong He, Chelsea Dumesny, Judith A. Carrall, Carolyn T. Dillon, Katja I. de Roo, Mal Eutick, Li Dong, Graham S. Baldwin and Mehrdad Nikfarjam
Int. J. Mol. Sci. 2024, 25(21), 11366; https://doi.org/10.3390/ijms252111366 - 22 Oct 2024
Viewed by 539
Abstract
Arsenic trioxide (ATO) has been shown to inhibit pancreatic cancer (PC) cell growth in vitro and to promote the inhibitory effects of gemcitabine (Gem) on PC in vivo. However, the high toxicity of ATO associated with the required high doses and indiscriminate [...] Read more.
Arsenic trioxide (ATO) has been shown to inhibit pancreatic cancer (PC) cell growth in vitro and to promote the inhibitory effects of gemcitabine (Gem) on PC in vivo. However, the high toxicity of ATO associated with the required high doses and indiscriminate targeting has limited its clinical application. This study aimed to determine whether coupling arsenic to a tumor homing peptide would increase the inhibitory potency against PC cells. The effects of this peptide-linked arsenic compound (PhAs-LHP), the analogous non-targeting arsenic compound (phenylarsine oxide, PAO), and marketed ATO on PC growth were tested in vitro and in a mouse model. The data demonstrated that PhAs-LHP inhibited PC cell growth in vitro more potently, with IC50 values 10 times lower than ATO. Like ATO, PhAs-LHP induced cell death and cell cycle arrest. This cytotoxic effect of PhAs-LHP was mediated via a macropinocytosis-linked uptake pathway as amiloride (a macropinocytosis inhibitor) reduced the inhibitory effect of PhAs-LHP. More importantly, PhAs-LHP inhibited PC growth in mice and enhanced the inhibitory effect of Gem on PC growth at 2 times lower molar concentration than PAO. These results indicate that PhAs-LHP inhibited PC more potently than ATO/PAO and suggest a potential clinical use for the combination of Gem with the peptide-linked arsenic compound for the treatment of pancreatic cancer. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

15 pages, 4670 KiB  
Article
Functions of Hemp-Induced Exosomes against Periodontal Deterioration Caused by Fine Dust
by Eunhee Kim, Yoonjin Park, Mihae Yun and Boyong Kim
Int. J. Mol. Sci. 2024, 25(19), 10331; https://doi.org/10.3390/ijms251910331 - 25 Sep 2024
Viewed by 859
Abstract
Although fine dust is linked to numerous health issues, including cardiovascular, neurological, respiratory, and cancerous diseases, research on its effects on oral health remains limited. In this study, we investigated the protective effects of mature hemp stem extract-induced exosomes (MSEIEs) on periodontal cells [...] Read more.
Although fine dust is linked to numerous health issues, including cardiovascular, neurological, respiratory, and cancerous diseases, research on its effects on oral health remains limited. In this study, we investigated the protective effects of mature hemp stem extract-induced exosomes (MSEIEs) on periodontal cells exposed to fine dust. Using various methods, including microRNA profiling, PCR, flow cytometry, immunocytochemistry, ELISA, and Alizarin O staining, we found that MSE treatment upregulated key microRNAs, such as hsa-miR-122-5p, hsa-miR-1301-3p, and hsa-let-7e-5p, associated with vital biological functions. MSEIEs exhibited three primary protective functions: suppressing inflammatory genes while activating anti-inflammatory ones, promoting the differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts and other cells, and regulating LL-37 and MCP-1 expression. These findings suggest that MSEIEs have potential as functional biomaterials for applications in pharmaceuticals, cosmetics, and food industries. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

18 pages, 601 KiB  
Article
Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer
by Rafał Watrowski, Eva Schuster, Toon Van Gorp, Gerda Hofstetter, Michael B. Fischer, Sven Mahner, Stefan Polterauer, Robert Zeillinger and Eva Obermayr
Int. J. Mol. Sci. 2024, 25(19), 10272; https://doi.org/10.3390/ijms251910272 - 24 Sep 2024
Viewed by 701
Abstract
Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 [...] Read more.
Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84–4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06–2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure A1

13 pages, 3580 KiB  
Article
Novel Function of Osteocalcin in Chondrocyte Differentiation and Endochondral Ossification Revealed on a CRISPR/Cas9 bglap–bglap2 Deficiency Mouse Model
by Xiang-Fang Yu, Bin Teng, Jun-Feng Li, Jian V. Zhang, Zhe Su and Pei-Gen Ren
Int. J. Mol. Sci. 2024, 25(18), 9945; https://doi.org/10.3390/ijms25189945 - 15 Sep 2024
Viewed by 914
Abstract
Endochondral ossification is the process by which cartilage is mineralized into bone, and is essential for the development of long bones. Osteocalcin (OCN), a protein abundant in bone matrix, also exhibits high expression in chondrocytes, especially hypertrophic chondrocytes, while its role in endochondral [...] Read more.
Endochondral ossification is the process by which cartilage is mineralized into bone, and is essential for the development of long bones. Osteocalcin (OCN), a protein abundant in bone matrix, also exhibits high expression in chondrocytes, especially hypertrophic chondrocytes, while its role in endochondral ossification remains unclear. Utilizing a new CRISPR/Cas9-mediated bglap–bglap2 deficiency (OCNem) mouse model generated in our laboratory, we provide the first evidence of OCN’s regulatory function in chondrocyte differentiation and endochondral ossification. The OCNem mice exhibited significant delays in primary and secondary ossification centers compared to wild-type mice, along with increased cartilage length in growth plates and hypertrophic zones during neonatal and adolescent stages. These anomalies indicated that OCN deficiency disturbed endochondral ossification during embryonic and postnatal periods. Mechanism wise, OCN deficiency was found to increase chondrocyte differentiation and postpone vascularization process. Furthermore, bone marrow mesenchymal stromal cells (BMSCs) from OCNem mice demonstrated an increased capacity for chondrogenic differentiation. Transcriptional network analysis implicated that BMP and TGF-β signaling pathways were highly affected in OCNem BMSCs, which is closely associated with cartilage development and maintenance. This elucidation of OCN’s function in chondrocyte differentiation and endochondral ossification contributes to a more comprehensive understanding of its impact on skeletal development and homeostasis. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

22 pages, 6264 KiB  
Article
Identification and Validation of STC1 Act as a Biomarker for High-Altitude Diseases and Its Pan-Cancer Analysis
by Qiong Li, Zhichao Xu, Qianhui Gong and Xiaobing Shen
Int. J. Mol. Sci. 2024, 25(16), 9085; https://doi.org/10.3390/ijms25169085 - 21 Aug 2024
Viewed by 1195
Abstract
High-altitude diseases, including acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE), are closely related to an individual’s ability to adapt to hypoxic environments. However, specific research in this field is relatively limited, and further biomarker research and clinical [...] Read more.
High-altitude diseases, including acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE), are closely related to an individual’s ability to adapt to hypoxic environments. However, specific research in this field is relatively limited, and further biomarker research and clinical trials are needed to clarify the exact role and potential therapeutic applications of key genes in high-altitude diseases. This study focuses on the role of the STC1 gene in high-altitude diseases and explores its expression patterns in different types of cancer. By using gene expression data analysis and functional experiments, we identified STC1 as a key gene affecting the development of altitude sickness. In addition, we also conducted expression and mutation analysis on STC1 in various cancer samples and found significant differences in the expression of this gene in 13 types of malignant tumors, which is associated with the hypoxic state in the tumor microenvironment. In addition, STC1 is significantly associated with patient prognosis and influences tumor immunity by mediating six types of immune cells (CD8+T cells, CD4+T cells, neutrophils, macrophages, monocytes, and B cells) in the tumor microenvironment. The expression and diagnostic value of STC1 were confirmed through GEO datasets and qPCR testing, indicating consistency with the results of bioinformatics analysis. These results indicate that STC1 is not only an important factor in the adaptive response to high-altitude diseases but may also play a role in the adaptation of cancer to low-oxygen environments. Our research provides a new perspective and potential targets for the discovery of biomarkers for high-altitude diseases and cancer treatment. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

17 pages, 6037 KiB  
Article
SOX2, JAGGED1, β-Catenin, and Vitamin D Receptor Expression Patterns during Early Development and Innervation of the Human Inner Ear
by Petra Mikulić, Marin Ogorevc, Marin Petričević, Dean Kaličanin, Robert Tafra, Mirna Saraga-Babić and Snježana Mardešić
Int. J. Mol. Sci. 2024, 25(16), 8719; https://doi.org/10.3390/ijms25168719 - 9 Aug 2024
Viewed by 1092
Abstract
Sensorineural hearing loss can be caused by lesions to the inner ear during development. Understanding the events and signaling pathways that drive inner ear formation is crucial for determining the possible causes of congenital hearing loss. We have analyzed the innervation and expression [...] Read more.
Sensorineural hearing loss can be caused by lesions to the inner ear during development. Understanding the events and signaling pathways that drive inner ear formation is crucial for determining the possible causes of congenital hearing loss. We have analyzed the innervation and expression of SOX2, JAGGED1, β-catenin (CTNNB1), and vitamin D receptor (VDR) in the inner ears of human conceptuses aged 5 to 10 weeks after fertilization (W) using immunohistochemistry. The prosensory domains of the human inner ear displayed SOX2 and JAGGED1 expression throughout the analyzed period, with SOX2 expression being more extensive in all the analyzed timepoints. Innervation of vestibular prosensory domains was present at 6 W and extensive at 10 W, while nerve fibers reached the base of the cochlear prosensory domain at 7–8 W. CTNNB1 and VDR expression was mostly membranous and present during all analyzed timepoints in the inner ear, being the strongest in the non-sensory epithelium. Their expression was stronger in the vestibular region compared to the cochlear duct. CTNNB1 and VDR expression displayed opposite expression trends during the analyzed period, but additional studies are needed to elucidate whether they interact during inner ear development. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

14 pages, 13074 KiB  
Article
Ectopic Activation of Fgf8 in Dental Mesenchyme Causes Incisor Agenesis and Molar Microdontia
by Yu Wang, Jingjing Wang, Tian Xu, Shuhui Yang, Xinran Wang, Lei Zhu, Nan Li, Bo Liu, Jing Xiao and Chao Liu
Int. J. Mol. Sci. 2024, 25(13), 7045; https://doi.org/10.3390/ijms25137045 - 27 Jun 2024
Viewed by 721
Abstract
Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in [...] Read more.
Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

16 pages, 8895 KiB  
Article
Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty
by Paula Aranda-Martínez, Ramy K. A. Sayed, José Fernández-Martínez, Yolanda Ramírez-Casas, Yang Yang, Germaine Escames and Darío Acuña-Castroviejo
Int. J. Mol. Sci. 2024, 25(11), 6166; https://doi.org/10.3390/ijms25116166 - 3 Jun 2024
Cited by 1 | Viewed by 1304
Abstract
Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative [...] Read more.
Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/μm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

13 pages, 656 KiB  
Review
Severe Hyperandrogenism in 46,XX Congenital Adrenal Hyperplasia: Molecular Physiopathology, Late Diagnoses, and Personalized Management
by Gianluca Cera, Andrea Corsello, Roberto Novizio, Vincenzo Di Donna, Pietro Locantore and Rosa Maria Paragliola
Int. J. Mol. Sci. 2024, 25(21), 11779; https://doi.org/10.3390/ijms252111779 - 2 Nov 2024
Viewed by 4183
Abstract
Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive endocrine disorders characterized by alteration in adrenal hormonal secretions. The most common form is caused by CYP21A2 mutations that result in 21-hydroxylase deficiency. Clinical features can vary, from salt-wasting forms, characterized by a [...] Read more.
Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive endocrine disorders characterized by alteration in adrenal hormonal secretions. The most common form is caused by CYP21A2 mutations that result in 21-hydroxylase deficiency. Clinical features can vary, from salt-wasting forms, characterized by a lack of mineralocorticoid activity with a risk of perinatal-onset adrenal crises, to “simple-virilizing” forms with sufficient aldosterone secretion, up to milder “non-classical” forms, with a variable grade of hyperandrogenism but no severe hormonal deficiencies. During pregnancy, CAH 46,XX fetuses are exposed to elevated androgen levels, leading to a variable grade of virilization and potential central nervous system effects if untreated. These patients are usually (but not always) assigned female at birth, but some cases may be misdiagnosed and assigned male, potentially inducing fertility, gender identity, and sexual behavior issues in adulthood. In these patients, the benefits and risks of a late gender transition should be carefully evaluated. In this paper, we reviewed the literature concerning the most interesting peculiarities of these conditions. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

30 pages, 1122 KiB  
Review
Sepsis Biomarkers: Advancements and Clinical Applications—A Narrative Review
by Rong-Rong He, Guo-Li Yue, Mei-Ling Dong, Jia-Qi Wang and Chen Cheng
Int. J. Mol. Sci. 2024, 25(16), 9010; https://doi.org/10.3390/ijms25169010 - 19 Aug 2024
Viewed by 3398
Abstract
Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and [...] Read more.
Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and accurate prognosis in sepsis management, which are pivotal for enhancing patient outcomes. Despite advances in supportive care, traditional biomarkers like C-reactive protein and procalcitonin have limitations, and recent studies have identified novel biomarkers with increased sensitivity and specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, protein C, triiodothyronine, and prokineticin 2. These emerging biomarkers hold promising potential for the early detection and prognostication of sepsis. They play a crucial role not only in diagnosis but also in guiding antibiotic therapy and evaluating treatment effectiveness. The introduction of point-of-care testing technologies has brought about a paradigm shift in biomarker application, enabling swift and real-time patient evaluation. Despite these advancements, challenges persist, notably concerning biomarker variability and the lack of standardized thresholds. This review summarizes the latest advancements in sepsis biomarker research, spotlighting the progress and clinical implications. It emphasizes the significance of multi-biomarker strategies and the feasibility of personalized medicine in sepsis management. Further verification of biomarkers on a large scale and their integration into clinical practice are advocated to maximize their efficacy in future sepsis treatment. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

17 pages, 828 KiB  
Review
Exploring the Utility of Long Non-Coding RNAs for Assessing the Health Consequences of Vaping
by Ahmad Besaratinia, Hannah Blumenfeld and Stella Tommasi
Int. J. Mol. Sci. 2024, 25(15), 8554; https://doi.org/10.3390/ijms25158554 - 5 Aug 2024
Viewed by 1631
Abstract
Electronic cigarette (e-cig) use, otherwise known as “vaping”, is widespread among adolescent never-smokers and adult smokers seeking a less-harmful alternative to combustible tobacco products. To date, however, the long-term health consequences of vaping are largely unknown. Many toxicants and carcinogens present in e-cig [...] Read more.
Electronic cigarette (e-cig) use, otherwise known as “vaping”, is widespread among adolescent never-smokers and adult smokers seeking a less-harmful alternative to combustible tobacco products. To date, however, the long-term health consequences of vaping are largely unknown. Many toxicants and carcinogens present in e-cig vapor and tobacco smoke exert their biological effects through epigenetic changes that can cause dysregulation of disease-related genes. Long non-coding RNAs (lncRNAs) have emerged as prime regulators of gene expression in health and disease states. A large body of research has shown that lncRNAs regulate genes involved in the pathogenesis of smoking-associated diseases; however, the utility of lncRNAs for assessing the disease-causing potential of vaping remains to be fully determined. A limited but growing number of studies has shown that lncRNAs mediate dysregulation of disease-related genes in cells and tissues of vapers as well as cells treated in vitro with e-cig aerosol extract. This review article provides an overview of the evolution of e-cig technology, trends in use, and controversies on the safety, efficacy, and health risks or potential benefits of vaping relative to smoking. While highlighting the importance of lncRNAs in cell biology and disease, it summarizes the current and ongoing research on the modulatory effects of lncRNAs on gene regulation and disease pathogenesis in e-cig users and in vitro experimental settings. The gaps in knowledge are identified, priorities for future research are highlighted, and the importance of empirical data for tobacco products regulation and public health is underscored. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

27 pages, 1592 KiB  
Review
A Glimpse into Humoral Response and Related Therapeutic Approaches of Takayasu’s Arteritis
by Shuning Guo, Yixiao Tian, Jing Li and Xiaofeng Zeng
Int. J. Mol. Sci. 2024, 25(12), 6528; https://doi.org/10.3390/ijms25126528 - 13 Jun 2024
Viewed by 1277
Abstract
Takayasu’s arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing [...] Read more.
Takayasu’s arteritis (TAK) manifests as an insidiously progressive and debilitating form of granulomatous inflammation including the aorta and its major branches. The precise etiology of TAK remains elusive, with current understanding suggesting an autoimmune origin primarily driven by T cells. Notably, a growing body of evidence bears testimony to the widespread effects of B cells on disease pathogenesis and progression. Distinct alterations in peripheral B cell subsets have been described in individuals with TAK. Advancements in technology have facilitated the identification of novel autoantibodies in TAK. Moreover, emerging data suggest that dysregulated signaling cascades downstream of B cell receptor families, including interactions with innate pattern recognition receptors such as toll-like receptors, as well as co-stimulatory molecules like CD40, CD80 and CD86, may result in the selection and proliferation of autoreactive B cell clones in TAK. Additionally, ectopic lymphoid neogenesis within the aortic wall of TAK patients exhibits functional characteristics. In recent decades, therapeutic interventions targeting B cells, notably utilizing the anti-CD20 monoclonal antibody rituximab, have demonstrated efficacy in TAK. Despite the importance of the humoral immune response, a systematic understanding of how autoreactive B cells contribute to the pathogenic process is still lacking. This review provides a comprehensive overview of the biological significance of B cell-mediated autoimmunity in TAK pathogenesis, as well as insights into therapeutic strategies targeting the humoral response. Furthermore, it examines the roles of T-helper and T follicular helper cells in humoral immunity and their potential contributions to disease mechanisms. We believe that further identification of the pathogenic role of autoimmune B cells and the underlying regulation system will lead to deeper personalized management of TAK patients. We believe that further elucidation of the pathogenic role of autoimmune B cells and the underlying regulatory mechanisms holds promise for the development of personalized approaches to managing TAK patients. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

15 pages, 4179 KiB  
Case Report
Mediastinal Teratoma with Nephroblastomatous Elements: Case Report, Literature Review, and Comparison with Maturing Fetal Glomerulogenic Zone/Definitive Zone Ratio and Nephrogenic Rests
by Bader Alfawaz, Khaldoun Koujok, Gilgamesh Eamer and Consolato M. Sergi
Int. J. Mol. Sci. 2024, 25(22), 12427; https://doi.org/10.3390/ijms252212427 - 19 Nov 2024
Viewed by 267
Abstract
Extrarenal teratoid Wilms’ tumor (TWT) is a variant of Wilms’ tumor with fewer than 30 cases reported in the literature. It comprises more than 50% heterologous tissue and presents a significant diagnostic challenge due to its complex histology. We report an unusual case [...] Read more.
Extrarenal teratoid Wilms’ tumor (TWT) is a variant of Wilms’ tumor with fewer than 30 cases reported in the literature. It comprises more than 50% heterologous tissue and presents a significant diagnostic challenge due to its complex histology. We report an unusual case of mediastinal teratoma with nephroblastomatous elements in an 8-year-old female. The patient presented with respiratory distress, fever, weight loss, and a large anterior mediastinal mass. Imaging revealed a heterogeneous tumor containing fat, fluid, and calcification, suggestive of a teratoma. Surgical resection confirmed a mature cystic teratoma with foci of nephroblastoma. Pathological analysis demonstrated a mixture of ectodermal, mesodermal, and endodermal tissues alongside nephroblastomatous components. Immunohistochemistry was positive for Wilms Tumor 1 and other relevant markers, confirming the diagnosis. The patient had an uneventful postoperative course and was discharged after three days. This case adds to the growing body of research on extrarenal TWT, particularly its occurrence in the mediastinum, a rare site for such tumors. A literature review highlighted that extrarenal TWT often affects children, typically presenting in the retroperitoneum or sacrococcygeal regions, with varying recurrence rates and long-term outcomes. This case underscores the importance of histopathological and immunohistochemical analysis in diagnosing TWT and differentiating it from other mediastinal tumors to ensure appropriate treatment planning, emphasizing the need for long-term follow-up due to the potential for recurrence or metastasis. This paper also provides an in-depth look at nephron development and nephrogenic rests, highlighting the structural and functional aspects of nephrogenesis and the factors that disrupt it in fetal kidneys. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

8 pages, 527 KiB  
Case Report
Mutations in Genes Encoding Subunits of the RNA Exosome as a Potential Novel Cause of Thrombotic Microangiopathy
by Kioa L. Wijnsma, Anne M. Schijvens, Romy N. Bouwmeester, Lonneke A. M. Aarts, Lambertus (Bert) P. van den Heuvel, Charlotte A. Haaxma and Nicole C. A. J. van de Kar
Int. J. Mol. Sci. 2024, 25(14), 7604; https://doi.org/10.3390/ijms25147604 - 11 Jul 2024
Viewed by 1300
Abstract
Thrombotic microangiopathy (TMA) in association with RNA exosome encoding mutations has only recently been recognized. Here, we present an infant (female) with an EXOSC5 mutation (c.230_232del p.Glu77del) associated with the clinical phenotype known as CABAC syndrome (cerebellar ataxia, brain abnormalities, and cardiac conduction [...] Read more.
Thrombotic microangiopathy (TMA) in association with RNA exosome encoding mutations has only recently been recognized. Here, we present an infant (female) with an EXOSC5 mutation (c.230_232del p.Glu77del) associated with the clinical phenotype known as CABAC syndrome (cerebellar ataxia, brain abnormalities, and cardiac conduction defects), including pontocerebellar hypoplasia, who developed renal TMA. At the age of four months, she presented with signs of septic illness, after which she developed TMA. A stool culture showed rotavirus as a potential trigger. The patient received eculizumab once, alongside supportive treatment, while awaiting diagnostic analysis of TMA, including genetic complement analysis, all of which were negative. Eculizumab was withdrawn and the patient’s TMA recovered quickly. A review of the literature identified an additional four patients (age < 1 year) who developed TMA after a viral trigger in the presence of mutations in EXOSC3. The recurrence of TMA in one of these patients with an EXOSC3 mutation while on eculizumab treatment underscores the apparent lack of responsiveness to C5 inhibition. In conclusion, mutations in genes influencing the RNA exosome, like EXOSC3 and EXOSC5, characterized by neurodevelopment and neurodegenerative disorders could potentially lead to TMA in the absence of complement dysregulation. Hence, these patients were likely non-responsive to eculizumab. Full article
(This article belongs to the Special Issue A Commemorative Special Issue in Honor of Prof. Giovanni De Toni: A Pediatrician and Innovator at the Gaslini Children’s Hospital, Genoa, Italy)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-15
Back to TopTop