Journal Description
International Journal of Molecular Sciences
International Journal of Molecular Sciences
is an international, peer-reviewed, open access journal providing an advanced forum for biochemistry, molecular and cell biology, molecular biophysics, molecular medicine, and all aspects of molecular research in chemistry, and is published semimonthly online by MDPI. The Australian Society of Plant Scientists (ASPS), Epigenetics Society, European Calcium Society (ECS), European Chitin Society (EUCHIS), Spanish Society for Cell Biology (SEBC) and others are affiliated with IJMS and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, MEDLINE, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Biochemistry & Molecular Biology) / CiteScore - Q1 (Inorganic Chemistry)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.3 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about the IJMS.
- Companion journals for IJMS include: Biophysica, Obesities, Stresses and Lymphatics.
Impact Factor:
5.6 (2022);
5-Year Impact Factor:
6.2 (2022)
Latest Articles
Comparison of RNA-Sequencing Methods for Degraded RNA
Int. J. Mol. Sci. 2024, 25(11), 6143; https://doi.org/10.3390/ijms25116143 (registering DOI) - 2 Jun 2024
Abstract
RNA sequencing (RNA-Seq) is a powerful technique and is increasingly being used in clinical research and drug development. Currently, several RNA-Seq methods have been developed. However, the relative advantage of each method for degraded RNA and low-input RNA, such as RNA samples collected
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RNA sequencing (RNA-Seq) is a powerful technique and is increasingly being used in clinical research and drug development. Currently, several RNA-Seq methods have been developed. However, the relative advantage of each method for degraded RNA and low-input RNA, such as RNA samples collected in the field of clinical setting, has remained unknown. The Standard method of RNA-Seq captures mRNA by poly(A) capturing using Oligo dT beads, which is not suitable for degraded RNA. Here, we used three commercially available RNA-Seq library preparation kits (SMART-Seq, xGen Broad-range, and RamDA-Seq) using random primer instead of Oligo dT beads. To evaluate the performance of these methods, we compared the correlation, the number of detected expressing genes, and the expression levels with the Standard RNA-Seq method. Although the performance of RamDA-Seq was similar to that of Standard RNA-Seq, the performance for low-input RNA and degraded RNA has decreased. The performance of SMART-Seq was better than xGen and RamDA-Seq in low-input RNA and degraded RNA. Furthermore, the depletion of ribosomal RNA (rRNA) improved the performance of SMART-Seq and xGen due to increased expression levels. SMART-Seq with rRNA depletion has relative advantages for RNA-Seq using low-input and degraded RNA.
Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
Whole Genome Scan Uncovers Candidate Genes Related to Milk Production Traits in Barka Cattle
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Wondossen Ayalew, Xiaoyun Wu, Getinet Mekuriaw Tarekegn, Tesfaye Sisay Tessema, Rakan Naboulsi, Renaud Van Damme, Erik Bongcam-Rudloff, Zewdu Edea, Min Chu, Solomon Enquahone, Chunnian Liang and Ping Yan
Int. J. Mol. Sci. 2024, 25(11), 6142; https://doi.org/10.3390/ijms25116142 (registering DOI) - 2 Jun 2024
Abstract
In this study, our primary aim was to explore the genomic landscape of Barka cattle, a breed recognized for high milk production in a semi-arid environment, by focusing on genes with known roles in milk production traits. We employed genome-wide analysis and three
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In this study, our primary aim was to explore the genomic landscape of Barka cattle, a breed recognized for high milk production in a semi-arid environment, by focusing on genes with known roles in milk production traits. We employed genome-wide analysis and three selective sweep detection methods (ZFST, θπ ratio, and ZHp) to identify candidate genes associated with milk production and composition traits. Notably, ACAA1, P4HTM, and SLC4A4 were consistently identified by all methods. Functional annotation highlighted their roles in crucial biological processes such as fatty acid metabolism, mammary gland development, and milk protein synthesis. These findings contribute to understanding the genetic basis of milk production in Barka cattle, presenting opportunities for enhancing dairy cattle production in tropical climates. Further validation through genome-wide association studies and transcriptomic analyses is essential to fully exploit these candidate genes for selective breeding and genetic improvement in tropical dairy cattle.
Full article
(This article belongs to the Special Issue Molecular Genetics and Breeding Mechanisms in Domestics Animals 2.0)
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Open AccessReview
mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process
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Sulaiman K. Marafie, Fahd Al-Mulla and Jehad Abubaker
Int. J. Mol. Sci. 2024, 25(11), 6141; https://doi.org/10.3390/ijms25116141 (registering DOI) - 2 Jun 2024
Abstract
The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset
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The mammalian target of rapamycin (mTOR) is a pivotal regulator, integrating diverse environmental signals to control fundamental cellular functions, such as protein synthesis, cell growth, survival, and apoptosis. Embedded in a complex network of signaling pathways, mTOR dysregulation is implicated in the onset and progression of a range of human diseases, including metabolic disorders such as diabetes and cardiovascular diseases, as well as various cancers. mTOR also has a notable role in aging. Given its extensive biological impact, mTOR signaling is a prime therapeutic target for addressing these complex conditions. The development of mTOR inhibitors has proven advantageous in numerous research domains. This review delves into the significance of mTOR signaling, highlighting the critical components of this intricate network that contribute to disease. Additionally, it addresses the latest findings on mTOR inhibitors and their clinical implications. The review also emphasizes the importance of developing more effective next-generation mTOR inhibitors with dual functions to efficiently target the mTOR pathways. A comprehensive understanding of mTOR signaling will enable the development of effective therapeutic strategies for managing diseases associated with mTOR dysregulation.
Full article
(This article belongs to the Special Issue mTOR in Metabolism and Cancer)
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Open AccessArticle
The Multifaceted Actions of PVP–Curcumin for Treating Infections
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Magdalena Metzger, Stefan Manhartseder, Leonie Krausgruber, Lea Scholze, David Fuchs, Carina Wagner, Michaela Stainer, Johannes Grillari, Andreas Kubin, Lionel Wightman and Peter Dungel
Int. J. Mol. Sci. 2024, 25(11), 6140; https://doi.org/10.3390/ijms25116140 (registering DOI) - 2 Jun 2024
Abstract
Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP–curcumin as a photosensitizer
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Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP–curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP–curcumin concentrations (1–200 µg/mL) and 475 nm blue light (7.5–45 J/cm²). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP–curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP–curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP–curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.
Full article
(This article belongs to the Special Issue Molecular Aspects of Photodynamic Therapy)
Open AccessCommunication
Lead Decreases Bone Morphogenetic Protein-7 (BMP-7) Expression and Increases Renal Cell Carcinoma Growth in a Sex-Divergent Manner
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Elizabeth A. Grunz, Haley Anderson, Rebecka M. Ernst, Spencer Price, D’Artanyan Good, Victoria Vieira-Potter and Alan R. Parrish
Int. J. Mol. Sci. 2024, 25(11), 6139; https://doi.org/10.3390/ijms25116139 (registering DOI) - 2 Jun 2024
Abstract
Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.5 μM lead
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Both tissue and blood lead levels are elevated in renal cell carcinoma (RCC) patients. These studies assessed the impact of the subchronic lead challenge on the progression of RCC in vitro and in vivo. Lead challenge of Renca cells with 0.5 μM lead acetate for 10 consecutive passages decreased E-cadherin expression and cell aggregation. Proliferation, colony formation, and wound healing were increased. When lead-challenged cells were injected into mice, tumor size at day 21 was increased; interestingly, this increase was seen in male but not female mice. When mice were challenged with 32 ppm lead in drinking water for 20 weeks prior to tumor cell injection, there was an increase in tumor size in male, but not female, mice at day 21. To investigate the mechanism underlying the sex differences, the expression of sex hormone receptors in Renca cells was examined. Control Renca cells expressed estrogen receptor (ER) alpha but not ER beta or androgen receptor (AR), as assessed by qPCR, and the expression of ERα was increased in tumors in both sexes. In tumor samples harvested from lead-challenged cells, both ERα and AR were detected by qPCR, yet there was a significant decrease in AR seen in lead-challenged tumor cells from male mice only. This was paralleled by a plate-based array demonstrating the same sex difference in BMP-7 gene expression, which was also significantly decreased in tumors harvested from male but not female mice; this finding was validated by immunohistochemistry. A similar expression pattern was seen in tumors harvested from the mice challenged with lead in the drinking water. These data suggest that lead promotes RCC progression in a sex-dependent via a mechanism that may involve sex-divergent changes in BMP-7 expression.
Full article
(This article belongs to the Special Issue Metals and Cancer)
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Open AccessArticle
Orthologs of NOX5 and EC-SOD/SOD3: dNox and dSod3 Impact Egg Hardening Process and Egg Laying in Reproductive Function of Drosophila melanogaster
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Eva Louise Steinmetz, Annika Scherer, Célestine Calvet and Uli Müller
Int. J. Mol. Sci. 2024, 25(11), 6138; https://doi.org/10.3390/ijms25116138 (registering DOI) - 2 Jun 2024
Abstract
The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the ineffectiveness of the antioxidative defense mechanisms. Primary sources of ROS are respiratory electron transfer and the activity of NADPH oxidases (NOX) while
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The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the ineffectiveness of the antioxidative defense mechanisms. Primary sources of ROS are respiratory electron transfer and the activity of NADPH oxidases (NOX) while superoxide dismutases (SOD) are the main key regulators that control the levels of ROS and reactive nitrogen species intra- and extracellularly. Because of their central role SODs are the subject of research on human ovarian dysfunction but sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study we clarify the localization of the ROS-producing enzyme dNox within the ovaries of Drosophila melanogaster and by a tissue-specific knockdown we show that dNox-derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg-laying behavior but not the chorion hardening process.
Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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Open AccessArticle
Rhodamine 19 Alkyl Esters as Effective Antibacterial Agents
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Pavel A. Nazarov, Vladislav S. Maximov, Alexander M. Firsov, Marina V. Karakozova, Veronika Panfilova, Elena A. Kotova, Maxim V. Skulachev and Yuri N. Antonenko
Int. J. Mol. Sci. 2024, 25(11), 6137; https://doi.org/10.3390/ijms25116137 (registering DOI) - 2 Jun 2024
Abstract
Mitochondria-targeted antioxidants (MTAs) have been studied quite intensively in recent years as potential therapeutic agents and vectors for the delivery of other active substances to mitochondria and bacteria. Their most studied representatives are MitoQ and SkQ1, with its fluorescent rhodamine analog SkQR1, a
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Mitochondria-targeted antioxidants (MTAs) have been studied quite intensively in recent years as potential therapeutic agents and vectors for the delivery of other active substances to mitochondria and bacteria. Their most studied representatives are MitoQ and SkQ1, with its fluorescent rhodamine analog SkQR1, a decyl ester of rhodamine 19 carrying plastoquinone. In the present work, we observed a pronounced antibacterial action of SkQR1 against Gram-positive bacteria, but virtually no effect on Gram-negative bacteria. The MDR pump AcrAB-TolC, known to expel SkQ1, did not recognize and did not pump out SkQR1 and dodecyl ester of rhodamine 19 (C12R1). Rhodamine 19 butyl (C4R1) and ethyl (C2R1) esters more effectively suppressed the growth of ΔtolC Escherichia coli, but lost their potency with the wild-type E. coli pumping them out. The mechanism of the antibacterial action of SkQR1 may differ from that of SkQ1. The rhodamine derivatives also proved to be effective antibacterial agents against various Gram-positive species, including Staphylococcus aureus and Mycobacterium smegmatis. By using fluorescence correlation spectroscopy and fluorescence microscopy, SkQR1 was shown to accumulate in the bacterial membrane. Thus, the presentation of SkQR1 as a fluorescent analogue of SkQ1 and its use for visualization should be performed with caution.
Full article
(This article belongs to the Special Issue Advanced Research of Mitochondria-Targeted Antioxidants)
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Open AccessReview
First Trimester Placental Biomarkers for Pregnancy Outcomes
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Martina Cristodoro, Martina Messa, Giovanni Tossetta, Daniela Marzioni, Marinella Dell’Avanzo, Annalisa Inversetti and Nicoletta Di Simone
Int. J. Mol. Sci. 2024, 25(11), 6136; https://doi.org/10.3390/ijms25116136 (registering DOI) - 2 Jun 2024
Abstract
The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies
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The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.
Full article
(This article belongs to the Special Issue Molecular Research in Pregnancy, Childbirth, and Related Complications)
Open AccessArticle
Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection
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Jorge Lindo, Célia Nogueira, Rui Soares, Nuno Cunha, Maria Rosário Almeida, Lisa Rodrigues, Patrícia Coelho, Francisco Rodrigues, Rodrigo A. Cunha and Teresa Gonçalves
Int. J. Mol. Sci. 2024, 25(11), 6135; https://doi.org/10.3390/ijms25116135 (registering DOI) - 2 Jun 2024
Abstract
SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study
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SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions.
Full article
(This article belongs to the Special Issue The Role and Mechanism of P2X7 Receptor in Cancer and Inflammatory Diseases)
Open AccessArticle
In Vitro Cell Culture Model for Osteoclast Activation during Estrogen Withdrawal
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Nisha Gandhi, Safia Omer and Rene E. Harrison
Int. J. Mol. Sci. 2024, 25(11), 6134; https://doi.org/10.3390/ijms25116134 (registering DOI) - 1 Jun 2024
Abstract
Estrogen (17β-estradiol) deficiency post-menopause alters bone homeostasis whereby bone resorption by osteoclasts exceeds bone formation by osteoblasts, leading to osteoporosis in females. We established an in vitro model to examine the consequences of estrogen withdrawal (E2-WD) on osteoclasts derived from the mouse macrophage
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Estrogen (17β-estradiol) deficiency post-menopause alters bone homeostasis whereby bone resorption by osteoclasts exceeds bone formation by osteoblasts, leading to osteoporosis in females. We established an in vitro model to examine the consequences of estrogen withdrawal (E2-WD) on osteoclasts derived from the mouse macrophage RAW 264.7 cell line and utilized it to investigate the mechanism behind the enhanced osteoclast activity post-menopause. We found that a greater population of osteoclasts that underwent E2-WD contained a podosome belt necessary for osteoclasts to adhere and resorb bone and possessed elevated resorptive activity compared to osteoclasts exposed to estrogen (E2) continuously. Our results show that compared to osteoclasts that received E2 continuously, those that underwent E2-WD had a faster rate of microtubule (MT) growth, reduced RhoA activation, and shorter podosome lifespan. Thus, altered podosome and MT dynamics induced by the withdrawal of estrogen supports podosome belt assembly/stability in osteoclasts, which may explain their enhanced bone resorption activity.
Full article
(This article belongs to the Section Molecular Biology)
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Open AccessArticle
The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis
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Chenyang Wang, Kyosuke Oishi, Tadahiro Kobayashi, Ko Fujii, Motoki Horii, Natsumi Fushida, Tasuku Kitano, Shintaro Maeda, Yuichi Ikawa, Akito Komuro, Yasuhito Hamaguchi and Takashi Matsushita
Int. J. Mol. Sci. 2024, 25(11), 6133; https://doi.org/10.3390/ijms25116133 (registering DOI) - 1 Jun 2024
Abstract
The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role
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The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription–polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.
Full article
(This article belongs to the Special Issue News in Skin Diseases: From Basic Mechanisms to Therapies)
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Open AccessArticle
AMELX Mutations and Genotype–Phenotype Correlation in X-Linked Amelogenesis Imperfecta
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Shih-Kai Wang, Hong Zhang, Hua-Chieh Lin, Yin-Lin Wang, Shu-Chun Lin, Figen Seymen, Mine Koruyucu, James P. Simmer and Jan C.-C. Hu
Int. J. Mol. Sci. 2024, 25(11), 6132; https://doi.org/10.3390/ijms25116132 (registering DOI) - 1 Jun 2024
Abstract
AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop’s classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for
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AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop’s classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a “snow-capped” appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype–phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5′ truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3′ truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by “toxic” cellular effects of the mutant proteins.
Full article
(This article belongs to the Special Issue Molecular Metabolism of Ameloblasts in Tooth Development)
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Open AccessArticle
Integrative Metabolomics, Enzymatic Activity, and Gene Expression Analysis Provide Insights into the Metabolic Profile Differences between the Slow-Twitch Muscle and Fast-Twitch Muscle of Pseudocaranx dentex
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Huan Wang, Busu Li, Ang Li, Changting An, Shufang Liu and Zhimeng Zhuang
Int. J. Mol. Sci. 2024, 25(11), 6131; https://doi.org/10.3390/ijms25116131 (registering DOI) - 1 Jun 2024
Abstract
The skeletal muscles of teleost fish encompass heterogeneous muscle types, termed slow-twitch muscle (SM) and fast-twitch muscle (FM), characterized by distinct morphological, anatomical, histological, biochemical, and physiological attributes, driving different swimming behaviors. Despite the central role of metabolism in regulating skeletal muscle types
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The skeletal muscles of teleost fish encompass heterogeneous muscle types, termed slow-twitch muscle (SM) and fast-twitch muscle (FM), characterized by distinct morphological, anatomical, histological, biochemical, and physiological attributes, driving different swimming behaviors. Despite the central role of metabolism in regulating skeletal muscle types and functions, comprehensive metabolomics investigations focusing on the metabolic differences between these muscle types are lacking. To reveal the differences in metabolic characteristics between the SM and FM of teleost, we conducted an untargeted metabolomics analysis using Pseudocaranx dentex as a representative model and identified 411 differential metabolites (DFMs), of which 345 exhibited higher contents in SM and 66 in FM. KEGG enrichment analysis showed that these DFMs were enriched in the metabolic processes of lipids, amino acids, carbohydrates, purines, and vitamins, suggesting that there were significant differences between the SM and FM in multiple metabolic pathways, especially in the metabolism of energy substances. Furthermore, an integrative analysis of metabolite contents, enzymatic activity assays, and gene expression levels involved in ATP-PCr phosphate, anaerobic glycolysis, and aerobic oxidative energy systems was performed to explore the potential regulatory mechanisms of energy metabolism differences. The results unveiled a set of differential metabolites, enzymes, and genes between the SM and FM, providing compelling molecular evidence of the FM achieving a higher anaerobic energy supply capacity through the ATP-PCr phosphate and glycolysis energy systems, while the SM obtains greater energy supply capacity via aerobic oxidation. These findings significantly advance our understanding of the metabolic profiles and related regulatory mechanisms of skeletal muscles, thereby expanding the knowledge of metabolic physiology and ecological adaptation in teleost fish.
Full article
(This article belongs to the Special Issue Molecular Research on Skeletal Muscle Biology)
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Open AccessArticle
Knockdown of Esr1 from DRD1-Rich Brain Regions Affects Adipose Tissue Metabolism: Potential Crosstalk between Nucleus Accumbens and Adipose Tissue
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Dusti Shay, Rebecca Welly, Jiude Mao, Jessica Kinkade, Joshua K. Brown, Cheryl S. Rosenfeld and Victoria J. Vieira-Potter
Int. J. Mol. Sci. 2024, 25(11), 6130; https://doi.org/10.3390/ijms25116130 (registering DOI) - 1 Jun 2024
Abstract
Declining estrogen (E2) leads to physical inactivity and adipose tissue (AT) dysfunction. Mechanisms are not fully understood, but E2’s effects on dopamine (DA) activity in the nucleus accumbens (NAc) brain region may mediate changes in mood and voluntary physical activity (PA). Our prior
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Declining estrogen (E2) leads to physical inactivity and adipose tissue (AT) dysfunction. Mechanisms are not fully understood, but E2’s effects on dopamine (DA) activity in the nucleus accumbens (NAc) brain region may mediate changes in mood and voluntary physical activity (PA). Our prior work revealed that loss of E2 robustly affected NAc DA-related gene expression, and the pattern correlated with sedentary behavior and visceral fat. The current study used a new transgenic mouse model (D1ERKO) to determine whether the abolishment of E2 receptor alpha (ERa) signaling within DA-rich brain regions affects PA and AT metabolism. Adult male and female wild-type (WT) and D1ERKO (KD) mice were assessed for body composition, energy intake (EE), spontaneous PA (SPA), and energy expenditure (EE); underwent glucose tolerance testing; and were assessed for blood biochemistry. Perigonadal white AT (PGAT), brown AT (BAT), and NAc brain regions were assessed for genes and proteins associated with DA, E2 signaling, and metabolism; AT sections were also assessed for uncoupling protein (UCP1). KD mice had greater lean mass and EE (genotype effects) and a visible change in BAT phenotype characterized by increased UCP1 staining and lipid depletion, an effect seen only among females. Female KD had higher NAc Oprm1 transcript levels and greater PGAT UCP1. This group tended to have improved glucose tolerance (p = 0.07). NAc suppression of Esr1 does not appear to affect PA, yet it may directly affect metabolism. This work may lead to novel targets to improve metabolic dysfunction following E2 loss, possibly by targeting the NAc.
Full article
(This article belongs to the Special Issue Advances in the Understanding of Adipose Tissue Biology and Energy Metabolism 2.0)
Open AccessArticle
Study on the Structure and Properties of Silk Fibers Obtained from Factory All-Age Artificial Diets
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Mengyao Pan, Kexin Jiang, Yuwei Jin, Ying Mao, Wangyang Lu, Wenbin Jiang and Wenxing Chen
Int. J. Mol. Sci. 2024, 25(11), 6129; https://doi.org/10.3390/ijms25116129 (registering DOI) - 1 Jun 2024
Abstract
The traditional production mode of the sericulture industry is no longer suitable for the development requirements of modern agriculture; to facilitate the sustainable development of the sericulture industry, factory all-age artificial diet feeding came into being. Understanding the structural characteristics and properties of
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The traditional production mode of the sericulture industry is no longer suitable for the development requirements of modern agriculture; to facilitate the sustainable development of the sericulture industry, factory all-age artificial diet feeding came into being. Understanding the structural characteristics and properties of silk fibers obtained from factory all-age artificial diet feeding is an important prerequisite for application in the fields of textiles, clothing, biomedicine, and others. However, there have been no reports so far. In this paper, by feeding silkworms with factory all-age artificial diets (AD group) and mulberry leaves (ML group), silk fibers were obtained via two different feeding methods. The structure, mechanical properties, hygroscopic properties, and degradation properties were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Structurally, no new functional groups appeared in the AD group. Compared with the ML group, the structure of the two groups was similar, and there was no significant difference in mechanical properties and moisture absorption. The structure of degummed silk fibers is dominated by crystalline regions, but α-chymotrypsin hydrolyzes the amorphous regions of silk proteins, so that after 28 d of degradation, the weight loss of both is very small. This provides further justification for the feasibility of factory all-age artificial diets for silkworms.
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(This article belongs to the Section Materials Science)
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Open AccessCommunication
Next-Generation Sequencing of the Human Aqueous Humour Microbiome
by
Günther Schlunck, Philip Maier, Barbara Maier, Wolfgang Maier, Sebastian Strempel, Thomas Reinhard and Sonja Heinzelmann
Int. J. Mol. Sci. 2024, 25(11), 6128; https://doi.org/10.3390/ijms25116128 (registering DOI) - 1 Jun 2024
Abstract
The microbiome of the ocular surface has been characterised, but only limited information is available on a possible silent intraocular microbial colonisation in normal eyes. Therefore, we performed next-generation sequencing (NGS) of 16S rDNA genes in the aqueous humour. The aqueous humour was
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The microbiome of the ocular surface has been characterised, but only limited information is available on a possible silent intraocular microbial colonisation in normal eyes. Therefore, we performed next-generation sequencing (NGS) of 16S rDNA genes in the aqueous humour. The aqueous humour was sampled from three patients during cataract surgery. Air swabs, conjunctival swabs from patients as well as from healthy donors served as controls. Following DNA extraction, the V3 and V4 hypervariable regions of the 16S rDNA gene were amplified and sequenced followed by denoising. The resulting Amplicon Sequence Variants were matched to a subset of the Ribosomal Database Project 16S database. The deduced bacterial community was then statistically analysed. The DNA content in all samples was low (0–1.49 ng/µL) but sufficient for analysis. The main phyla in the samples were Acinetobacteria (48%), Proteobacteria (26%), Firmicutes (14%), Acidobacteria (8%), and Bacteroidetes (2%). Patients’ conjunctival control samples and anterior chamber fluid showed similar patterns of bacterial species containing many waterborne species. Non-disinfected samples showed a different bacterial spectrum than the air swab samples. The data confirm the existence of an ocular surface microbiome. Meanwhile, a distinct intraocular microbiome was not discernible from the background, suggesting the absence of an intraocular microbiome in normal eyes.
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(This article belongs to the Special Issue New Insights into Gene Expression Regulation in the Next-Generation Sequencing (NGS) Era)
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Open AccessArticle
Gene Regulatory Network Controlling Flower Development in Spinach (Spinacia oleracea L.)
by
Yaying Ma, Wenhui Fu, Suyan Wan, Yikai Li, Haoming Mao, Ehsan Khalid, Wenping Zhang and Ray Ming
Int. J. Mol. Sci. 2024, 25(11), 6127; https://doi.org/10.3390/ijms25116127 (registering DOI) - 1 Jun 2024
Abstract
Spinach (Spinacia oleracea L.) is a dioecious, diploid, wind-pollinated crop cultivated worldwide. Sex determination plays an important role in spinach breeding. Hence, this study aimed to understand the differences in sexual differentiation and floral organ development of dioecious flowers, as well as
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Spinach (Spinacia oleracea L.) is a dioecious, diploid, wind-pollinated crop cultivated worldwide. Sex determination plays an important role in spinach breeding. Hence, this study aimed to understand the differences in sexual differentiation and floral organ development of dioecious flowers, as well as the differences in the regulatory mechanisms of floral organ development of dioecious and monoecious flowers. We compared transcriptional-level differences between different genders and identified differentially expressed genes (DEGs) related to spinach floral development, as well as sex-biased genes to investigate the flower development mechanisms in spinach. In this study, 9,189 DEGs were identified among the different genders. DEG analysis showed the participation of four main transcription factor families, MIKC_MADS, MYB, NAC, and bHLH, in spinach flower development. In our key findings, abscisic acid (ABA) and gibberellic acid (GA) signal transduction pathways play major roles in male flower development, while auxin regulates both male and female flower development. By constructing a gene regulatory network (GRN) for floral organ development, core transcription factors (TFs) controlling organ initiation and growth were discovered. This analysis of the development of female, male, and monoecious flowers in spinach provides new insights into the molecular mechanisms of floral organ development and sexual differentiation in dioecious and monoecious plants in spinach.
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(This article belongs to the Special Issue Functional and Structural Genomics Studies for Plant Breeding)
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hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice
by
Wei Chen, Sharon Y. Kim, Alicia Lee, Yun-Jeong Kim, Chungyu Chang, Hung Ton-That, Reuben Kim, Sangjae Kim and No-Hee Park
Int. J. Mol. Sci. 2024, 25(11), 6126; https://doi.org/10.3390/ijms25116126 (registering DOI) - 1 Jun 2024
Abstract
GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various
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GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer’s disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.
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(This article belongs to the Special Issue Advances in Molecular and Translational Medicine 2.0)
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Open AccessReview
Nanoengineered Silica-Based Biomaterials for Regenerative Medicine
by
Mohamed A. A. Abdelhamid, Hazim O. Khalifa, Mi-Ran Ki and Seung Pil Pack
Int. J. Mol. Sci. 2024, 25(11), 6125; https://doi.org/10.3390/ijms25116125 (registering DOI) - 1 Jun 2024
Abstract
The paradigm of regenerative medicine is undergoing a transformative shift with the emergence of nanoengineered silica-based biomaterials. Their unique confluence of biocompatibility, precisely tunable porosity, and the ability to modulate cellular behavior at the molecular level makes them highly desirable for diverse tissue
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The paradigm of regenerative medicine is undergoing a transformative shift with the emergence of nanoengineered silica-based biomaterials. Their unique confluence of biocompatibility, precisely tunable porosity, and the ability to modulate cellular behavior at the molecular level makes them highly desirable for diverse tissue repair and regeneration applications. Advancements in nanoengineered silica synthesis and functionalization techniques have yielded a new generation of versatile biomaterials with tailored functionalities for targeted drug delivery, biomimetic scaffolds, and integration with stem cell therapy. These functionalities hold the potential to optimize therapeutic efficacy, promote enhanced regeneration, and modulate stem cell behavior for improved regenerative outcomes. Furthermore, the unique properties of silica facilitate non-invasive diagnostics and treatment monitoring through advanced biomedical imaging techniques, enabling a more holistic approach to regenerative medicine. This review comprehensively examines the utilization of nanoengineered silica biomaterials for diverse applications in regenerative medicine. By critically appraising the fabrication and design strategies that govern engineered silica biomaterials, this review underscores their groundbreaking potential to bridge the gap between the vision of regenerative medicine and clinical reality.
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(This article belongs to the Special Issue Application of Nanotechnology in Regenerative Medicine)
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Genome-Wide Transcriptomic and Metabolomic Analyses Unveiling the Defence Mechanisms of Populus tremula against Sucking and Chewing Insect Herbivores
by
Filip Pastierovič, Kanakachari Mogilicherla, Jaromír Hradecký, Alina Kalyniukova, Ondřej Dvořák, Amit Roy and Ivana Tomášková
Int. J. Mol. Sci. 2024, 25(11), 6124; https://doi.org/10.3390/ijms25116124 (registering DOI) - 1 Jun 2024
Abstract
Plants and insects coevolved as an evolutionarily successful and enduring association. The molecular arms race led to evolutionary novelties regarding unique mechanisms of defence and detoxification in plants and insects. While insects adopt mechanisms to conquer host defence, trees develop well-orchestrated and species-specific
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Plants and insects coevolved as an evolutionarily successful and enduring association. The molecular arms race led to evolutionary novelties regarding unique mechanisms of defence and detoxification in plants and insects. While insects adopt mechanisms to conquer host defence, trees develop well-orchestrated and species-specific defence strategies against insect herbivory. However, current knowledge on the molecular underpinnings of fine-tuned tree defence responses against different herbivore insects is still restricted. In the current study, using a multi-omics approach, we unveiled the defence response of Populus tremula against aphids (Chaitophorus populialbae) and spongy moths (Lymantria dispar) herbivory. Comparative differential gene expression (DGE) analyses revealed that around 272 and 1203 transcripts were differentially regulated in P. tremula after moth and aphid herbivory compared to uninfested controls. Interestingly, 5716 transcripts were differentially regulated in P. tremula between aphids and moth infestation. Further investigation showed that defence-related stress hormones and their lipid precursors, transcription factors, and signalling molecules were over-expressed, whereas the growth-related counterparts were suppressed in P. tremula after aphid and moth herbivory. Metabolomics analysis documented that around 37% of all significantly abundant metabolites were associated with biochemical pathways related to tree growth and defence. However, the metabolic profiles of aphid and moth-fed trees were quite distinct, indicating species-specific response optimization. After identifying the suitable reference genes in P. tremula, the omics data were further validated using RT-qPCR. Nevertheless, our findings documented species-specific fine-tuning of the defence response of P. tremula, showing conservation on resource allocation for defence overgrowth under aphid and moth herbivory. Such findings can be exploited to enhance our current understanding of molecular orchestration of tree responses against herbivory and aid in developing insect pest resistance P. tremula varieties.
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(This article belongs to the Special Issue New Insights into Plants and Insects Interactions)
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