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Curr. Issues Mol. Biol., Volume 46, Issue 6 (June 2024) – 74 articles

Cover Story (view full-size image): Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. MS development and progression depend on the perpetuation of chronic inflammation and high oxidative stress production, which are attributable to several factors, such as infections, an unhealthy diet, autoimmune responses, genetic predisposition, and gut microbiota alterations. In recent years, several studies suggest supplementing traditional treatments with the use of bioactive molecules (e.g., ubiquinone, resveratrol, curcumin, epigallocatechin gallate, citicoline, ellagic acid, boswellic acid, and plant extracts) and dietary interventions (Mediterranean vs. ketogenic) that, acting as antioxidants and anti-inflammatory agents, can help counteract neuroinflammation and oxidative damage. View this paper
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16 pages, 2856 KiB  
Article
Selection of Reference Genes for Expression Normalization by RT-qPCR in Dracocephalum moldavica L.
by Shasha Li, Xiaomin Ge, Guoqing Bai and Chen Chen
Curr. Issues Mol. Biol. 2024, 46(6), 6284-6299; https://doi.org/10.3390/cimb46060375 - 20 Jun 2024
Viewed by 152
Abstract
Dracocephalum moldavica is widely used as an ornamental, medicine, and perfume in industry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) is widely and accurately utilized for gene expression evaluations. Selecting optimal reference genes is essential for normalizing RT-qPCR results. However, the identification of [...] Read more.
Dracocephalum moldavica is widely used as an ornamental, medicine, and perfume in industry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) is widely and accurately utilized for gene expression evaluations. Selecting optimal reference genes is essential for normalizing RT-qPCR results. However, the identification of suitable reference genes in D. moldavica has not been documented. A total of 12 reference genes in D. moldavica were identified by PEG6000 (15%) treatment under hypertonia conditions in different tissues (roots, stem, leaves, flower, seeds and sepal) and during three stages of flower development, then used to validate the expression stability. There were four algorithms (delta Ct, geNorm, NormFinder, and BestKeeper) used to analyze the stability. Finally, the RefFinder program was employed to evaluate the candidate reference genes’ stability. The results showed that ACTIN, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and EF1α (elongation factor-1α) were stable reference genes under the PEG6000 treatment. Heat shock protein 70 (HSP70) was the most stable gene across different flower development stages. ADP-ribosylation factor (ARF) was the most stable gene in different tissues and total samples. This study provides reliable gene expression studies for future research in D. moldavica. Full article
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17 pages, 3569 KiB  
Article
Low Levels of IgM Recognizing 4-Hydroxy-2-Nonenal-Modified Apolipoprotein A-I Peptide and Its Association with the Severity of Coronary Artery Disease in Taiwanese Patients
by Meng-Huan Lei, Po-Wen Hsu, Yin-Tai Tsai, Chen-Chi Chang, I-Jung Tsai, Hung Hsu, Ming-Hui Cheng, Ying-Li Huang, Hung-Tse Lin, Yu-Cheng Hsu and Ching-Yu Lin
Curr. Issues Mol. Biol. 2024, 46(6), 6267-6283; https://doi.org/10.3390/cimb46060374 - 20 Jun 2024
Viewed by 169
Abstract
Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels [...] Read more.
Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251–262 and ApoA-I70–83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251–262 HNE, IgM anti-ApoA-I70–83 HNE, IgG anti-ApoA-I251–262, IgG anti-ApoA-I70–83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251–262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251–262 HNE may increase the severity of CAD at high and low levels, respectively. Full article
(This article belongs to the Special Issue A Focus on the Molecular Basis of Cardiovascular Diseases)
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19 pages, 1723 KiB  
Review
The Omics Revolution in Understanding Chicken Reproduction: A Comprehensive Review
by Armughan Ahmed Wadood and Xiquan Zhang
Curr. Issues Mol. Biol. 2024, 46(6), 6248-6266; https://doi.org/10.3390/cimb46060373 - 20 Jun 2024
Viewed by 204
Abstract
Omics approaches have significantly contributed to our understanding of several aspects of chicken reproduction. This review paper gives an overview of the use of omics technologies such as genomics, transcriptomics, proteomics, and metabolomics to elucidate the mechanisms of chicken reproduction. Genomics has transformed [...] Read more.
Omics approaches have significantly contributed to our understanding of several aspects of chicken reproduction. This review paper gives an overview of the use of omics technologies such as genomics, transcriptomics, proteomics, and metabolomics to elucidate the mechanisms of chicken reproduction. Genomics has transformed the study of chicken reproduction by allowing the examination of the full genetic makeup of chickens, resulting in the discovery of genes associated with reproductive features and disorders. Transcriptomics has provided insights into the gene expression patterns and regulatory mechanisms involved in reproductive processes, allowing for a better knowledge of developmental stages and hormone regulation. Furthermore, proteomics has made it easier to identify and quantify the proteins involved in reproductive physiology to better understand the molecular mechanisms driving fertility, embryonic development, and egg quality. Metabolomics has emerged as a useful technique for understanding the metabolic pathways and biomarkers linked to reproductive performance, providing vital insights for enhancing breeding tactics and reproductive health. The integration of omics data has resulted in the identification of critical molecular pathways and biomarkers linked with chicken reproductive features, providing the opportunity for targeted genetic selection and improved reproductive management approaches. Furthermore, omics technologies have helped to create biomarkers for fertility and embryonic viability, providing the poultry sector with tools for effective breeding and reproductive health management. Finally, omics technologies have greatly improved our understanding of chicken reproduction by revealing the molecular complexities that underpin reproductive processes. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)
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11 pages, 8423 KiB  
Article
SRSF3 Knockdown Inhibits Lipopolysaccharide-Induced Inflammatory Response in Macrophages
by Yu Fu, Yanjing Wang, Luyao Zhang, Tianliu He, Weiye Shi, Xueling Guo and Yingze Wang
Curr. Issues Mol. Biol. 2024, 46(6), 6237-6247; https://doi.org/10.3390/cimb46060372 - 20 Jun 2024
Viewed by 157
Abstract
Serine/arginine-rich splicing factor 3 (SRSF3), the smallest member of the SR protein family, serves multiple roles in RNA processing, including splicing, translation, and stability. Recent studies have shown that SRSF3 is implicated in several inflammatory diseases. However, its impact on macrophage inflammation remains [...] Read more.
Serine/arginine-rich splicing factor 3 (SRSF3), the smallest member of the SR protein family, serves multiple roles in RNA processing, including splicing, translation, and stability. Recent studies have shown that SRSF3 is implicated in several inflammatory diseases. However, its impact on macrophage inflammation remains unclear. Herein, we determined the expression of SRSF3 in inflammatory macrophages and found that the level of SRSF3 was increased in macrophages within atherosclerotic plaques, as well as in RAW-264.7 macrophages stimulated by lipopolysaccharides. Moreover, the downregulation of SRSF3 suppressed the levels of inflammatory cytokines by deactivating the nuclear factor κB (NFκB) pathway. Furthermore, the alternative splicing of myeloid differentiation protein 2 (MD2), a co-receptor of toll-like receptor 4 (TLR4), is regulated by SRSF3. The depletion of SRSF3 increased the level of the shorter MD2B splicing variants, which contributed to inflammatory inhibition in macrophages. In conclusion, our findings imply that SRSF3 regulates lipopolysaccharide-stimulated inflammation, in part by controlling the alternative splicing of MD2 mRNA in macrophages. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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14 pages, 1765 KiB  
Article
Oxytocin Exhibits Neuroprotective Effects on Hippocampal Cultures under Severe Oxygen–Glucose Deprivation Conditions
by Mara Ioana Ionescu, Ioana-Florentina Grigoras, Rosana-Bristena Ionescu, Diana Maria Chitimus, Robert Mihai Haret, Bogdan Ianosi, Mihai Ceanga and Ana-Maria Zagrean
Curr. Issues Mol. Biol. 2024, 46(6), 6223-6236; https://doi.org/10.3390/cimb46060371 - 19 Jun 2024
Viewed by 346
Abstract
Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen–glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may [...] Read more.
Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen–glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may confound any measured treatment effect. Oxytocin (OXT) has emerged as a potential neuroprotective agent against the deleterious effects of PA. Previous studies have demonstrated OXT’s potential to enhance neuronal survival in immature hippocampal cultures exposed to OGD, possibly by modulating gamma-aminobutyric acid-A receptor activity. Moreover, OXT’s precise impact on developing hippocampal neurons under different severities of OGD/PA remains uncertain. In this study, we investigated the effects of OXT (0.1 µM and 1 µM) on 7-day-old primary rat hippocampal cultures subjected to 2 h OGD/sham normoxic conditions. Cell culture viability was determined using the resazurin assay. Our results indicate that the efficacy of 1 µM OXT treatment varied according to the severity of the OGD-induced lesion, exhibiting a protective effect (p = 0.022) only when cellular viability dropped below 49.41% in non-treated OGD cultures compared to normoxic ones. Furthermore, administration of 0.1 µM OXT did not yield significant effects, irrespective of lesion severity (p > 0.05). These findings suggest that 1 µM OXT treatment during OGD confers neuroprotection exclusively in severe lesions in hippocampal neurons after 7 days in vitro. Further research is warranted to elucidate the mechanisms involved in OXT-mediated neuroprotection. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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24 pages, 9653 KiB  
Article
Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis
by Adán Arizmendi-Izazaga, Napoleón Navarro-Tito, Hilda Jiménez-Wences, Adilene Evaristo-Priego, Víctor Daniel Priego-Hernández, Roberto Dircio-Maldonado, Ana Elvira Zacapala-Gómez, Miguel Ángel Mendoza-Catalán, Berenice Illades-Aguiar, Mónica Ascención De Nova Ocampo, Eric Genaro Salmerón-Bárcenas, Marco Antonio Leyva-Vázquez and Julio Ortiz-Ortiz
Curr. Issues Mol. Biol. 2024, 46(6), 6199-6222; https://doi.org/10.3390/cimb46060370 - 19 Jun 2024
Viewed by 199
Abstract
Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell [...] Read more.
Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1β to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus. Full article
(This article belongs to the Special Issue Tumorigenesis and Tumor Microenvironment)
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13 pages, 2682 KiB  
Article
Structure and Phylogenetic Relationships of Scolopacidae Mitogenomes (Charadriiformes: Scolopacidae)
by Quanheng Li, Peiyue Jiang, Mingxuan Li, Jingjing Du, Jianxiang Sun, Nuo Chen, Yu Wu, Qing Chang and Chaochao Hu
Curr. Issues Mol. Biol. 2024, 46(6), 6186-6198; https://doi.org/10.3390/cimb46060369 - 19 Jun 2024
Viewed by 219
Abstract
The family Scolopacidae presents a valuable subject for evolutionary research; however, molecular studies of Scolopacidae are still relatively understudied, and the phylogenetic relationships of certain species remain unclear. In this study, we sequenced and obtained complete mitochondrial DNA (mtDNA) from Actitis hypoleucos and [...] Read more.
The family Scolopacidae presents a valuable subject for evolutionary research; however, molecular studies of Scolopacidae are still relatively understudied, and the phylogenetic relationships of certain species remain unclear. In this study, we sequenced and obtained complete mitochondrial DNA (mtDNA) from Actitis hypoleucos and partial mtDNA from Numenius arquata, Limosa limosa, and Limnodromus semipalmatus. The complete mtDNA contained 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 tRNA genes, and a control region. Scolopacidae contained three types of start codons and five types of stop codons (including one incomplete stop codon, T--). In 13 protein-coding genes, average uncorrected pairwise distances (Aupd) revealed that ATP8 was the least conserved while COX3 had the lowest evolutionary rate. The ratio of Ka/Ks suggested that all PCGs were under purifying selection. Using two methods (maximum likelihood and Bayesian inference) to analyze the phylogenetic relationships of the family Scolopacidae, it was found that the genera Xenus and Actitis were clustered into another sister group, while the genus Phalaropus is more closely related to the genus Tringa. The genera Limnodromus, Gallinago, and Scolopax form a monophyletic group. This study improves our understanding of the evolutionary patterns and phylogenetic relationships of the family Scolopacidae. Full article
(This article belongs to the Special Issue Mitochondrial Genome 2024)
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17 pages, 2626 KiB  
Article
Molecular Approaches Detect Early Signals of Programmed Cell Death in Hippolyte inermis Leach
by Francesca Glaviano, Roberta Esposito, Emanuele Somma, Amir Sagi, Eliahu D. Aflalo, Maria Costantini and Valerio Zupo
Curr. Issues Mol. Biol. 2024, 46(6), 6169-6185; https://doi.org/10.3390/cimb46060368 - 18 Jun 2024
Viewed by 224
Abstract
The protandric shrimp Hippolyte inermis is the only known marine invertebrate whose sex determination is strongly influenced by the composition of its food. In H. inermis, a sex reversal is triggered by the ingestion of diatoms of the genus Cocconeis associated with [...] Read more.
The protandric shrimp Hippolyte inermis is the only known marine invertebrate whose sex determination is strongly influenced by the composition of its food. In H. inermis, a sex reversal is triggered by the ingestion of diatoms of the genus Cocconeis associated with leaves of the seagrass Posidonia oceanica. These diatoms contain compounds that promote programmed cell death (PCD) in H. inermis and also in human cancer cells. Transcriptomic analyses suggested that ferroptosis is the primary trigger of the shrimp’s sex reversal, leading to the rapid destruction of the androgen gland (AG) followed by a chain of apoptotic events transforming the testes into ovaries. Here, we propose a molecular approach to detect the effects of compounds stimulating the PCD. An RNA extraction method, suitable for young shrimp post-larvae (five days after metamorphosis; PL5 stage), was established. In addition, six genes involved in apoptosis, four involved in ferroptosis, and seven involved in the AG switch were mined from the transcriptome, and their expression levels were followed using real-time qPCR in PL5 fed on Cocconeis spp., compared to PL5 fed on a basic control feed. Our molecular approach, which detected early signals of sex reversal, represents a powerful instrument for investigating physiological progression and patterns of PCD in marine invertebrates. It exemplifies the physiological changes that may start a few days after the settlement of post-larvae and determine the life destiny of an individual. Full article
(This article belongs to the Special Issue Mitochondrial Genome 2024)
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30 pages, 2899 KiB  
Review
Molecular Biomarkers of Canine Reproductive Functions
by Marzena Mogielnicka-Brzozowska and Aleksandra Wiktoria Cichowska
Curr. Issues Mol. Biol. 2024, 46(6), 6139-6168; https://doi.org/10.3390/cimb46060367 - 17 Jun 2024
Viewed by 270
Abstract
The aim of the current study is to review potential molecular biomarker substances selected so far as useful for assessing the quality of dog semen. Proteins, lipids, carbohydrates, and ions can serve as molecular biomarkers of reproductive functions (BRFs) for evaluating male reproductive [...] Read more.
The aim of the current study is to review potential molecular biomarker substances selected so far as useful for assessing the quality of dog semen. Proteins, lipids, carbohydrates, and ions can serve as molecular biomarkers of reproductive functions (BRFs) for evaluating male reproductive health and identifying potential risk factors for infertility or reproductive disorders. Evaluation of BRF levels in semen samples or reproductive tissues may provide insights into the underlying causes of infertility, such as impaired sperm function, abnormal sperm–egg interaction, or dysfunction of the male reproductive tract. Molecular biomarker proteins may be divided into two groups: proteins that are well-studied, such as A-kinase anchoring proteins (AKAPs), albumins (ALBs), alkaline phosphatase (ALPL), clusterin (CLU), canine prostate-specific esterase (CPSE), cysteine-rich secretory protein 2 (CRISP2), lactotransferrin (LTF), metalloproteinases (MMPs), and osteopontin (OPN) and proteins that are not well-studied. Non-protein markers include lipid-based substances (fatty acids, phosphatidylcholine), carbohydrates (glycosaminoglycans), and ions (zinc, calcium). Assessing the levels of BRFs in semen samples may provide valuable information for breeding management and reproductive assessments in dogs. This review systematizes current knowledge that could serve as a starting point for developing practical tests with the use of biomarkers of canine reproductive functions and their predictive value for assisted reproductive technique outcomes and semen preservation. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)
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18 pages, 1853 KiB  
Article
Antidepressant Effect of Enzymatic Porcine Placenta Hydrolysate in Repeated Immobilization Stress-Induced Ovariectomized Female Mice
by Minsook Ye, Sharon Nguyen, Min Ju Kim, Jee Sun Hwang, Gun Won Bae, Keun-Hang Susan Yang and Insop Shim
Curr. Issues Mol. Biol. 2024, 46(6), 6121-6138; https://doi.org/10.3390/cimb46060366 - 17 Jun 2024
Viewed by 244
Abstract
When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study [...] Read more.
When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic the symptoms of women with menopause-related depression, a stressed ovariectomized (OVX) female mouse model was used to evaluate the antidepressant effects of EPPH. The female mice were randomly divided into five groups: (1) the sham-operated (Sham) group, (2) the OVX + repeated stress + saline-treated (OVX + ST) group, (3) the OVX + repeated stress + estradiol (0.2 mg/kg)-treated (positive control) group, (4) the OVX + repeated stress + EPPH (300 mg/kg)-treated (300) group, and (5) the OVX + repeated stress + EPPH (1500 mg/kg)-treated (1500) group. Female mice were OVX and repeatedly immobilization-stressed for 2 weeks (2 h/day). A tail suspension test was conducted on the 13th day, followed by the forced swimming test on the 14th day to assess the antidepressant effects of EPPH. After the behavioral tests, the levels of CORT, PGE2, and IL-1β were evaluated. In addition, c-Fos expression in the paraventricular nucleus (PVN) was evaluated using immunohistochemistry. The concentrations of NO, PGE2, and IL-1β stimulated by LPS were significantly reduced via the addition of EPPH to RAW 264.7 cells. EPPH significantly promoted neurite outgrowth in PC12 cells compared to that of the controls. In the tail suspension test, the duration of immobility was reduced in mice treated with EPPH 1500 compared to the OVX + ST group. The EPPH 1500 group had significantly decreased levels of c-Fos-positive neurons in the PVN and reduced levels of CORT and IL-1β in the serum of the Sham group. These results suggested that the high dose of EPPH administration induced the antidepressant-like effect in the ovariectomized mice with repeated stress via downregulating the levels of CORT, IL-1β, and PGE2 in the serum through reducing the expression of c-Fos in the PVN regions. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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9 pages, 772 KiB  
Case Report
Obesity as a Confounding Factor in the Diagnosis of Wilson’s Disease: Case Report of Two Siblings with the Same Genotype but Different Clinical Courses
by Emanuele Bracciamà, Annamaria Sapuppo, Laura Rapisarda, Enrico Siciliano, Anna Caciotti, Amelia Morrone, Martino Ruggieri, Giuseppina Cantarella, Renato Bernardini and Gaetano Bertino
Curr. Issues Mol. Biol. 2024, 46(6), 6112-6120; https://doi.org/10.3390/cimb46060365 - 17 Jun 2024
Viewed by 314
Abstract
Wilson’s disease (WD) is a biallelic disease-causing variant in the ATP7B gene on chromosome 13q14.3 that results in copper accumulation in many organs, particularly the liver and brain. The phenotypic spectrum is wide and symptoms at onset can be heterogeneous. We describe two [...] Read more.
Wilson’s disease (WD) is a biallelic disease-causing variant in the ATP7B gene on chromosome 13q14.3 that results in copper accumulation in many organs, particularly the liver and brain. The phenotypic spectrum is wide and symptoms at onset can be heterogeneous. We describe two Sicilian siblings, a young man and his elder sister, both compound heterozygous for the variants c.1286-2A>G and c.2668G>A (p.Val890Met) in the ATB7B gene. The male patient presented with liver cirrhosis, which quickly progressed to end-stage liver disease (Child–Pugh score = C10), while his sister had moderate steatotic liver disease (SLD). Our findings highlight that SLD may not always be related to obesity in overweight patients, especially when there are other potential risk factors such as a family history of chronic liver disease, or the persistence of high transaminase despite the adoption of adequate dietary and pharmacological intervention. Screening for conditions such as WD could identify patients at risk of developing SLD and avoid delays in diagnosis. Phenotypic variability in WD is considerable; therefore, further studies are needed to identify which WD patients have a greater risk of developing SLD and determine factors that can predict the severity of the disease. Full article
(This article belongs to the Section Molecular Medicine)
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12 pages, 3423 KiB  
Article
Anti-Inflammatory Response of New Postbiotics in TNF-α/IFN-γ-Induced Atopic Dermatitis-like HaCaT Keratinocytes
by Yoo-Kyung Kim, Minji Cho and Dae-Jung Kang
Curr. Issues Mol. Biol. 2024, 46(6), 6100-6111; https://doi.org/10.3390/cimb46060364 - 17 Jun 2024
Viewed by 240
Abstract
This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax china L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads [...] Read more.
This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax china L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of the heat-killed probiotics Lactobacillus acidophilus (LAC) and Lactobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-κB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers, such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-κB activation compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its therapeutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, presenting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fermentation process. Full article
(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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15 pages, 721 KiB  
Article
Stable Production of a Tethered Recombinant Eel Luteinizing Hormone Analog with High Potency in CHO DG44 Cells
by Munkhzaya Byambaragchaa, Sei Hyen Park, Sang-Gwon Kim, Min Gyu Shin, Shin-Kwon Kim, Sung-Pyo Hur, Myung-Hum Park, Myung-Hwa Kang and Kwan-Sik Min
Curr. Issues Mol. Biol. 2024, 46(6), 6085-6099; https://doi.org/10.3390/cimb46060363 - 15 Jun 2024
Viewed by 376
Abstract
We produced a recombinant eel luteinizing hormone (rec-eel LH) analog with high potency in Chinese hamster ovary DG44 (CHO DG44) cells. The tethered eel LH mutant (LH-M), which had a linker comprising the equine chorionic gonadotropin (eLH/CG) β-subunit carboxyl-terminal peptide (CTP) region (amino [...] Read more.
We produced a recombinant eel luteinizing hormone (rec-eel LH) analog with high potency in Chinese hamster ovary DG44 (CHO DG44) cells. The tethered eel LH mutant (LH-M), which had a linker comprising the equine chorionic gonadotropin (eLH/CG) β-subunit carboxyl-terminal peptide (CTP) region (amino acids 115 to 149), was inserted between the β-subunit and α-subunit of wild-type tethered eel LH (LH-wt). Monoclonal cells transfected with the tethered eel LH-wt and eel LH-M plasmids were isolated from five to nine clones of CHO DG44 cells, respectively. The secreted quantities abruptly increased on day 3, with peak levels of 5000–7500 ng/mL on day 9. The molecular weight of tethered rec-eel LH-wt was 32–36 kDa, while that of tethered rec-eel LH-M increased to approximately 38–44 kDa, indicating the detection of two bands. Treatment with the peptide N-glycanase F decreased the molecular weight by approximately 8 kDa. The oligosaccharides at the eCG β-subunit O-linked glycosylation sites were appropriately modified post-translation. The EC50 value and maximal responsiveness of eel LH-M increased by approximately 2.90- and 1.29-fold, respectively, indicating that the mutant exhibited more potent biological activity than eel LH-wt. Phosphorylated extracellular regulated kinase (pERK1/2) activation resulted in a sharp peak 5 min after agonist treatment, with a rapid decrease thereafter. These results indicate that the new tethered rec-eel LH analog had more potent activity in cAMP response than the tethered eel LH-wt in vitro. Taken together, this new eel LH analog can be produced in large quantities using a stable CHO DG44 cell system. Full article
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16 pages, 353 KiB  
Review
Candida auris Updates: Outbreak Evaluation through Molecular Assays and Antifungal Stewardship—A Narrative Review
by Silvia Ionescu, Ionut Luchian, Costin Damian, Ancuta Goriuc, Elena Porumb-Andrese, Cosmin Gabriel Popa, Roxana Gabriela Cobzaru, Carmen Ripa and Ramona Gabriela Ursu
Curr. Issues Mol. Biol. 2024, 46(6), 6069-6084; https://doi.org/10.3390/cimb46060362 - 15 Jun 2024
Viewed by 279
Abstract
Candida auris was reported by the WHO as second to Cryptococcus neoformans, in the list of nineteen fungal priority pathogens, along with two species with a new nomenclature, Nakaseomyces glabrata (Candida glabrata) and Pichia kudriavzevii (Candida krusei). This [...] Read more.
Candida auris was reported by the WHO as second to Cryptococcus neoformans, in the list of nineteen fungal priority pathogens, along with two species with a new nomenclature, Nakaseomyces glabrata (Candida glabrata) and Pichia kudriavzevii (Candida krusei). This novel classification was based on antifungal resistance, the number of deaths, evidence-based treatment, access to diagnostics, annual incidence, and complications and sequelae. We assessed which molecular assays have been used to diagnose Candida auris outbreaks in the last five years. Using “Candida auris; outbreak; molecular detection” as keywords, our search in PubMed revealed 32 results, from which we selected 23 original papers published in 2019–2024. The analyzed studies revealed that the detection methods were very different: from the VITEK® 2 System to MALDI TOF (Matrix-Assisted Laser Desorption Ionization–Time of Flight), NGS (Next-Generation Sequencing), WGS (Whole Genome Sequencing), and commercially available real-time PCR (Polymerase Chain Reaction) assays. Moreover, we identified studies that detected antifungal resistance genes (e.g., FKS for echinocandins and ERG11 for azoles). The analyzed outbreaks were from all continents, which confirms the capability of this yeast to spread between humans and to contaminate the environment. It is important that real-time PCR assays were developed for accurate and affordable detection by all laboratories, including the detection of antifungal resistance genes. This will allow the fast and efficient implementation of stewardship programs in hospitals. Full article
17 pages, 812 KiB  
Review
Cadmium Stress Signaling Pathways in Plants: Molecular Responses and Mechanisms
by Valentina Vitelli, Agnese Giamborino, Andrea Bertolini, Alessandro Saba and Andrea Andreucci
Curr. Issues Mol. Biol. 2024, 46(6), 6052-6068; https://doi.org/10.3390/cimb46060361 - 14 Jun 2024
Viewed by 175
Abstract
Heavy metal (HM) pollution, specifically cadmium (Cd) contamination, is a worldwide concern for its consequences for plant health and ecosystem stability. This review sheds light on the intricate mechanisms underlying Cd toxicity in plants and the various strategies employed by these organisms to [...] Read more.
Heavy metal (HM) pollution, specifically cadmium (Cd) contamination, is a worldwide concern for its consequences for plant health and ecosystem stability. This review sheds light on the intricate mechanisms underlying Cd toxicity in plants and the various strategies employed by these organisms to mitigate its adverse effects. From molecular responses to physiological adaptations, plants have evolved sophisticated defense mechanisms to counteract Cd stress. We highlighted the role of phytochelatins (PCn) in plant detoxification, which chelate and sequester Cd ions to prevent their accumulation and minimize toxicity. Additionally, we explored the involvement of glutathione (GSH) in mitigating oxidative damage caused by Cd exposure and discussed the regulatory mechanisms governing GSH biosynthesis. We highlighted the role of transporter proteins, such as ATP-binding cassette transporters (ABCs) and heavy metal ATPases (HMAs), in mediating the uptake, sequestration, and detoxification of Cd in plants. Overall, this work offered valuable insights into the physiological, molecular, and biochemical mechanisms underlying plant responses to Cd stress, providing a basis for strategies to alleviate the unfavorable effects of HM pollution on plant health and ecosystem resilience. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)
11 pages, 1319 KiB  
Communication
Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer
by Hao Sha and Weifeng Zhu
Curr. Issues Mol. Biol. 2024, 46(6), 6041-6051; https://doi.org/10.3390/cimb46060360 - 14 Jun 2024
Viewed by 218
Abstract
Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables [...] Read more.
Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables and issues of reverse causation. This study used a two-way two-sample Mendelian randomization (MR) method to test the hypothesized genetic causal relationship between PUFAs and PC risk. Data from an extensive genome-wide association study (GWAS) were analyzed, focusing on FAω3 and FAω6 levels, their ratios, and DHA as variables and PC incidence as outcomes. This relationship was comprehensively evaluated using related MR methods, such as inverse variance weighting (IVW), MR Egger, and weighted median (WM). This study finds a significant negative correlation between FAω3 and DHA levels and PC risk, while FAω6 levels show no significant correlation. Interestingly, the ratio of FAω6 to FAω3 was positively associated with increased risk of PC. Neither the MR Egger nor the MR-PRESSO tests detected significant pleiotropy, nor did the Cochrane’s Q test show significant heterogeneity. Leave-one-out analyzes further confirmed the robustness of these results. Using MR analysis of two samples, this study provides genetic causal evidence that FAω3 and DHA levels reduce the risk of PC, whereas the ratio of FAω6 to FAω3 increases the risk of PC. These insights highlight the potential utility of supplementing FAω3 and DHA or altering PUFAs in developing PC prevention strategies. Full article
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23 pages, 5266 KiB  
Article
Anti-Melanogenic and Anti-Inflammatory Effects of 2′-Hydroxy-4′,6′-dimethoxychalcone in B16F10 and RAW264.7 Cells
by Sungmin Bae, Jung-No Lee and Chang-Gu Hyun
Curr. Issues Mol. Biol. 2024, 46(6), 6018-6040; https://doi.org/10.3390/cimb46060359 - 14 Jun 2024
Viewed by 277
Abstract
Chalcone is a type of flavonoid compound that is widely biosynthesized in plants. Studies have shown that consuming flavonoids from fruits and vegetables or applying individual ingredients reduces the risk of skin disease. However, the effects of chalcone on melanogenesis and inflammation have [...] Read more.
Chalcone is a type of flavonoid compound that is widely biosynthesized in plants. Studies have shown that consuming flavonoids from fruits and vegetables or applying individual ingredients reduces the risk of skin disease. However, the effects of chalcone on melanogenesis and inflammation have not been fully investigated. The aim of this study was to evaluate the anti-melanogenic and anti-inflammatory effects of 2′-hydroxy-3,4′-dimethoxychalcone (3,4′-DMC), 2′-hydroxy-4,4′-dimethoxychalcone (4,4′-DMC), 2′-hydroxy-3′,4′-dimethoxychalcone (3′,4′-DMC), and 2′-hydroxy-4′,6′-dimethoxychalcone (4′,6′-DMC). Among the derivatives of 2′-hydroxy-4′-methoxychalcone, 4′,6′-DMC demonstrated the most potent melanogenesis-inhibitory and anti-inflammatory effects. As evidenced by various biological assays, 4′,6′-DMC showed no cytotoxicity and notably decreased the expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 enzymes. Furthermore, it reduced cellular melanin content and intracellular tyrosinase activity in B16F10 melanoma cells by downregulating microphthalmia-associated transcription factor (MITF), cAMP-dependent protein kinase (PKA), cAMP response element-binding protein (CREB), p38, c-Jun N-terminal kinase (JNK), β-catenin, glycogen synthase kinase-3β (GSK3β), and protein kinase B (AKT) proteins, while upregulating extracellular signal-regulated kinase (ERK) and p-β-catenin. Additionally, treatment with 4′,6′-DMC significantly mitigated the lipopolysaccharide (LPS)-induced expression of NO, PGE2, inflammatory cytokines, COX-2, and iNOS proteins. Overall, 4′,6′-DMC treatment notably alleviated LPS-induced damage by reducing nuclear factor kappa B (NF-κB), p38, JNK protein levels, and NF-kB/p65 nuclear translocation. Finally, the topical applicability of 4′,6′-DMC was evaluated in a preliminary human skin irritation test and no adverse effects were found. These findings suggest that 4′,6′-DMC may offer new possibilities for use as functional ingredients in cosmeceuticals and ointments. Full article
(This article belongs to the Special Issue Natural Product in Skin Inflammation and Barrier Function Damage)
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19 pages, 1540 KiB  
Review
The Neuromuscular Disorder Mediated by Extracellular Vesicles in Amyotrophic Lateral Sclerosis
by Elisabetta Carata, Marco Muci, Simona Di Giulio, Tiziano Di Giulio, Stefania Mariano and Elisa Panzarini
Curr. Issues Mol. Biol. 2024, 46(6), 5999-6017; https://doi.org/10.3390/cimb46060358 - 14 Jun 2024
Viewed by 318
Abstract
Amyotrophic lateral sclerosis (ALS) represents a neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons, resulting in muscular atrophy and eventual paralysis. While much research has concentrated on investigating the impact of major mutations associated with ALS on [...] Read more.
Amyotrophic lateral sclerosis (ALS) represents a neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons, resulting in muscular atrophy and eventual paralysis. While much research has concentrated on investigating the impact of major mutations associated with ALS on motor neurons and central nervous system (CNS) cells, recent studies have unveiled that ALS pathogenesis extends beyond CNS imbalances, encompassing dysregulation in other tissues such as skeletal muscle. Evidence from animal models and patients supports this broader perspective. Skeletal muscle, once considered solely as an effector organ, is now recognized as possessing significant secretory activity capable of influencing motor neuron survival. However, the precise cellular and molecular mechanisms underlying the detrimental effects observed in muscle and its associated structures in ALS remain poorly understood. Additionally, emerging data suggest that extracellular vesicles (EVs) may play a role in the establishment and function of the neuromuscular junction (NMJ) under both physiological and pathological conditions and in wasting and regeneration of skeletal muscles, particularly in neurodegenerative diseases like ALS. This review aims to explore the key findings about skeletal muscle involvement in ALS, shedding light on the potential underlying mechanisms and contributions of EVs and their possible application for the design of biosensors. Full article
(This article belongs to the Special Issue Exosomes and Extracellular Vesicles in Neuroprotection)
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15 pages, 2230 KiB  
Article
Antioxidant and Neuroprotective Effects of Fucoxanthin and Its Metabolite Fucoxanthinol: A Comparative In Vitro Study
by Letizia Pruccoli, Martina Balducci, Barbara Pagliarani and Andrea Tarozzi
Curr. Issues Mol. Biol. 2024, 46(6), 5984-5998; https://doi.org/10.3390/cimb46060357 - 14 Jun 2024
Viewed by 375
Abstract
Fucoxanthin is the most abundant carotenoid found in marine brown algae that exhibits several healthy properties. Dietary fucoxanthin is metabolized in the intestine, plasma, and other tissues to various metabolites, including fucoxanthinol. In this regard, the contribution of fucoxanthinol to the healthy properties [...] Read more.
Fucoxanthin is the most abundant carotenoid found in marine brown algae that exhibits several healthy properties. Dietary fucoxanthin is metabolized in the intestine, plasma, and other tissues to various metabolites, including fucoxanthinol. In this regard, the contribution of fucoxanthinol to the healthy properties of its precursor, fucoxanthin, against pathogenetic events associated with neurodegenerative diseases remains unexplored. Here, we evaluated and compared the antioxidant and neuroprotective effects of the carotenoids fucoxanthin and fucoxanthinol in in vitro models of Alzheimer’s (AD) and Parkinson’s (PD) disease. Neuronal SH-SY5Y cells were used to evaluate the antioxidant properties of the carotenoids against ABTS radical in the membrane and cytoplasm and oxidative stress elicited by tert-butyl hydroperoxide using the 2′,7′-dichlorodihydrofluorescein diacetate probe. We also assessed the ability of the carotenoids to increase the glutathione (GSH) and activate the Nrf2/Keap1/ARE pathway using the monochlorobimane probe and western blotting method, respectively. The neuroprotective effects of the carotenoids against the neurotoxicity generated by oligomers of Beta-Amyloid (1–42) peptide (OAβ) and 6-hydroxydopamine (6-OHDA), which are neurotoxins of AD and PD, respectively, were finally evaluated in the same neuronal cells using the thiazolyl blue tetrazolium bromide assay. Both carotenoids could reach the cytoplasm, which explains the mainly free radical scavenging activity at this level. Notably, fucoxanthinol had higher and lower antioxidant activity than fucoxanthin at extracellular and cellular levels. Although studied carotenoids exerted the ability to activate the Nrf2/Keap1/ARE pathway, leading to an increase of intracellular GSH, our results suggested that the antioxidant activity of the carotenoids could be mainly attributed to their radical scavenging activity in neuronal membrane and cytoplasm, where they accumulate. Fucoxanthinol also shared similar neuroprotective effects as fucoxanthin against the neurotoxicity generated by OAβ and 6-OHDA, suggesting a potential neuroprotective contribution to the action of fucoxanthin administered as a food supplement in in vivo experimental models. These results encourage further research to evaluate the bioavailability of fucoxanthinol and other metabolites of fucoxanthin at the brain level to elucidate the dietary neuroprotective potential of fucoxanthin. Full article
(This article belongs to the Special Issue Synthesis and Theoretical Study of Bioactive Molecules)
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19 pages, 949 KiB  
Review
MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options
by Yuming Shi, Erfan Taherifard, Ali Saeed and Anwaar Saeed
Curr. Issues Mol. Biol. 2024, 46(6), 5965-5983; https://doi.org/10.3390/cimb46060356 - 13 Jun 2024
Viewed by 231
Abstract
Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, [...] Read more.
Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC. Full article
(This article belongs to the Special Issue Tumorigenesis and Tumor Microenvironment)
15 pages, 937 KiB  
Review
Gastropod Allergy: A Comprehensive Narrative Review
by Elena Mederos-Luis, Paloma Poza-Guedes, Fernando Pineda, Inmaculada Sánchez-Machín and Ruperto González-Pérez
Curr. Issues Mol. Biol. 2024, 46(6), 5950-5964; https://doi.org/10.3390/cimb46060355 - 13 Jun 2024
Viewed by 306
Abstract
Food allergies have increased significantly in recent decades, with shellfish being a leading cause of food allergy and anaphylaxis worldwide, affecting both children and adults. The prevalence of shellfish allergies is estimated to be approximately 0.5–2.5% of the general population, varying significantly by [...] Read more.
Food allergies have increased significantly in recent decades, with shellfish being a leading cause of food allergy and anaphylaxis worldwide, affecting both children and adults. The prevalence of shellfish allergies is estimated to be approximately 0.5–2.5% of the general population, varying significantly by geographical location, age, and consumption habits. Although mollusk consumption has risen, the prevalence of mollusk allergies remains unknown. While extensive research has focused on crustacean allergies, mollusk allergies, particularly those related to gastropods, have received comparatively less attention. Clinical manifestations of shellfish allergy range from localized symptoms to life-threatening systemic reactions, such as anaphylaxis. Notably, severe bronchospasm is a predominant clinical feature in cases involving gastropods. Several allergens have been identified in mollusks, including paramyosin, tropomyosin, and sarcoplasmic calcium-binding protein. In gastropods, documented allergens include tropomyosin, paramyosin, the heavy chain of myosin, and Der p 4 amylase. Diagnosis typically involves a thorough clinical history, skin testing, in vitro quantification of immunoglobulin (Ig) E, and confirmation through an oral challenge, although the latter is reserved for selected cases. This narrative review highlights the limited research on gastropod allergy. It provides a comprehensive list of purified and recombinant allergens and discusses the applications of component-resolved diagnosis as well as current therapeutic developments. Full article
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21 pages, 1746 KiB  
Review
Unlocking the Potential: Semaglutide’s Impact on Alzheimer’s and Parkinson’s Disease in Animal Models
by Andreea Daniela Meca, Ianis Kevyn Stefan Boboc, Liliana Mititelu-Tartau and Maria Bogdan
Curr. Issues Mol. Biol. 2024, 46(6), 5929-5949; https://doi.org/10.3390/cimb46060354 - 13 Jun 2024
Viewed by 263
Abstract
Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This review provides a comprehensive description of SEM’s mechanism of action and its effects in [...] Read more.
Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). This review provides a comprehensive description of SEM’s mechanism of action and its effects in preclinical studies of these debilitating conditions. In animal models of AD, SEM has proved beneficial effects on multiple pathological hallmarks of the disease. SEM administration has been associated with reductions in amyloid-beta plaque deposition and mitigation of neuroinflammation. Moreover, SEM treatment has been shown to ameliorate behavioral deficits related to anxiety and social interaction. SEM-treated animals exhibit improvements in spatial learning and memory retention tasks, as evidenced by enhanced performance in maze navigation tests and novel object recognition assays. Similarly, in animal models of PD, SEM has demonstrated promising neuroprotective effects through various mechanisms. These include modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis. Additionally, SEM has been shown to improve motor function and ameliorate dopaminergic neuronal loss, offering the potential for disease-modifying treatment strategies. Overall, the accumulating evidence from preclinical studies suggests that SEM holds promise as a novel therapeutic approach for AD and PD. Further research is warranted to elucidate the underlying mechanisms of SEM’s neuroprotective effects and to translate these findings into clinical applications for the treatment of these devastating neurodegenerative disorders. Full article
(This article belongs to the Special Issue Molecules at Play in Neurological Diseases 2024)
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20 pages, 2441 KiB  
Article
Uropathogenic E. coli and Hybrid Pathotypes in Mexican Women with Urinary Tract Infections: A Comprehensive Molecular and Phenotypic Overview
by Manuel G. Ballesteros-Monrreal, Pablo Mendez-Pfeiffer, Bryan Ortíz, Enrique Bolado-Martínez, Maritza Lizeth Álvarez-Ainza, Yessica Enciso-Martínez, Margarita M. P. Arenas-Hernández, Betsaida Diaz-Murrieta, Edwin Barrios-Villa and Dora Valencia
Curr. Issues Mol. Biol. 2024, 46(6), 5909-5928; https://doi.org/10.3390/cimb46060353 - 13 Jun 2024
Viewed by 475
Abstract
Uropathogenic Escherichia coli (UPEC) is the main cause of urinary tract infections (UTIs) and carries virulence and resistance factors often found in mobilizable genetic elements, such as plasmids or pathogenicity islands (PAIs). UPEC is part of the extraintestinal pathogenic E. coli (ExPEC), but [...] Read more.
Uropathogenic Escherichia coli (UPEC) is the main cause of urinary tract infections (UTIs) and carries virulence and resistance factors often found in mobilizable genetic elements, such as plasmids or pathogenicity islands (PAIs). UPEC is part of the extraintestinal pathogenic E. coli (ExPEC), but hybrid strains possessing both diarrheagenic E. coli (DEC) and ExPEC traits, termed “hypervirulent”, present a significant health threat. This study assessed the prevalence of UPEC PAIs, ExPEC sequence types (ST), DEC genes, carbapenemase and extended-spectrum β-lactamase (ESBL) phenotypes, resistance genotypes, and plasmids in 40 clinical isolates of UPEC. Results showed that 72.5% of isolates had PAIs, mainly PAI IV536 (53%). ESBL phenotypes were found in 65% of β-lactam-resistant isolates, with 100% of carbapenem-resistant isolates producing carbapenemase. The predominant ESBL gene was blaCTX-M-2 (60%), and the most common resistance gene in fluoroquinolone and aminoglycoside-resistant isolates was aac(6′)Ib (93%). Plasmids were present in 57% of isolates, and 70% belonged to the ST131 clonal group. Molecular markers for DEC pathotypes were detected in 20 isolates, with 60% classified as hybrid pathotypes. These findings indicate significant pathogenic potential and the presence of hybrid pathotypes in E. coli UTI clinical isolates in the Mexican population. Full article
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15 pages, 1802 KiB  
Review
The Role of Licorice Chalcones as Molecular Genes and Signaling Pathways Modulator—A Review of Experimental Implications for Nicotine-Induced Non-Small Cell Lung Cancer Treatment
by Naser A. Alsharairi
Curr. Issues Mol. Biol. 2024, 46(6), 5894-5908; https://doi.org/10.3390/cimb46060352 - 13 Jun 2024
Viewed by 462
Abstract
Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation [...] Read more.
Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation of the nicotinic acetylcholine receptor (α7nAChR)-mediated cell-signaling pathways and molecular genes involved in proliferation, angiogenesis, and metastasis. Chalcones (CHs) and their derivatives are intermediate plant metabolites involved in flavonol biosynthesis. Isoliquiritigenin (ILTG), licochalcone A–E (LicoA–E), and echinatin (ECH) are the most common natural CHs isolated from the root of Glycyrrhiza (also known as licorice). In vitro and/or vivo experiments have shown that licorice CHs treatment exhibits a range of pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. Despite advances in NSCLC treatment, the mechanisms of licorice CHs in nicotine-induced NSCLC treatment remain unknown. Therefore, the aim of this paper is to review experimental studies through the PubMed/Medline database that reveal the effects of licorice CHs and their potential mechanisms in nicotine-induced NSCLC treatment. Full article
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13 pages, 3568 KiB  
Article
The Root Extract of Rosa multiflora Ameliorates Nonalcoholic Steatohepatitis Development via Blockade of De Novo Lipogenesis and Inflammation
by Nam-Hee Kim, Seung-Jin Lee, Kyeong-Jin Lee, Ae Ri Song, Hyun-Je Park, Jong Soo Kang, Joo Young Cha and Yong-Hyun Han
Curr. Issues Mol. Biol. 2024, 46(6), 5881-5893; https://doi.org/10.3390/cimb46060351 - 12 Jun 2024
Viewed by 212
Abstract
Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained [...] Read more.
Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation. Full article
(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)
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15 pages, 3653 KiB  
Article
Identification of a New B-Cell Epitope on the Capsid Protein of Avian Leukosis Virus and Its Application
by Zui Wang, Lina Liu, Junfeng Dou, Li Li, Qin Lu, Xinxin Jin, Huabin Shao, Zhengyu Cheng, Tengfei Zhang, Qingping Luo and Weicheng Bei
Curr. Issues Mol. Biol. 2024, 46(6), 5866-5880; https://doi.org/10.3390/cimb46060350 - 12 Jun 2024
Viewed by 233
Abstract
Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) [...] Read more.
Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 106.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that 218IIKYVLDRQK227 was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup’s specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV. Full article
(This article belongs to the Section Molecular Microbiology)
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21 pages, 1306 KiB  
Review
Sickle Cell Disease: Current Drug Treatments and Functional Foods with Therapeutic Potential
by Elisângela Gonçalves, Slim Smaoui, Miguel Brito, J. M. Oliveira, Ana Paula Arez and Loleny Tavares
Curr. Issues Mol. Biol. 2024, 46(6), 5845-5865; https://doi.org/10.3390/cimb46060349 - 12 Jun 2024
Viewed by 790
Abstract
Sickle cell anemia (SCA), the most common form of sickle cell disease (SCD), is a genetic blood disorder. Red blood cells break down prematurely, causing anemia and often blocking blood vessels, leading to chronic pain, organ damage, and increased infection risk. SCD arises [...] Read more.
Sickle cell anemia (SCA), the most common form of sickle cell disease (SCD), is a genetic blood disorder. Red blood cells break down prematurely, causing anemia and often blocking blood vessels, leading to chronic pain, organ damage, and increased infection risk. SCD arises from a single-nucleotide mutation in the β-globin gene, substituting glutamic acid with valine in the β-globin chain. This review examines treatments evaluated through randomized controlled trials for managing SCD, analyzes the potential of functional foods (dietary components with health benefits) as a complementary strategy, and explores the use of bioactive compounds as functional food ingredients. While randomized trials show promise for certain drugs, functional foods enriched with bioactive compounds also hold therapeutic potential. Further research is needed to confirm clinical efficacy, optimal dosages, and specific effects of these compounds on SCD, potentially offering a cost-effective and accessible approach to managing the disease. Full article
(This article belongs to the Special Issue Bioactive Molecules: Structure-Activity Relationship)
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20 pages, 1447 KiB  
Review
Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy
by Yiduo Liu, Han Li, Dejia Dai, Jiakang He and Zhengmin Liang
Curr. Issues Mol. Biol. 2024, 46(6), 5825-5844; https://doi.org/10.3390/cimb46060348 - 11 Jun 2024
Viewed by 277
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy [...] Read more.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) complex, is a zoonotic disease that remains one of the leading causes of death worldwide. Latent tuberculosis infection reactivation is a challenging obstacle to eradicating TB globally. Understanding the gene regulatory network of Mtb during dormancy is important. This review discusses up-to-date information about TB gene regulatory networks during dormancy, focusing on the regulation of lipid and energy metabolism, dormancy survival regulator (DosR), White B-like (Wbl) family, Toxin-Antitoxin (TA) systems, sigma factors, and MprAB. We outline the progress in vaccine and drug development associated with Mtb dormancy. Full article
(This article belongs to the Collection Feature Papers Collection in Molecular Microbiology)
13 pages, 4045 KiB  
Article
Biological Activities of Citrus-Derived Extracellular Vesicles on Human Cells: The Role of Preservation
by Theodora Karamanidou, Konstantinos Krommydas, Maria Karanikou, Dimitrios Tsamos, Konstantinos Michalakis, Dimitris Kletsas, Alexander Tsouknidas and Harris Pratsinis
Curr. Issues Mol. Biol. 2024, 46(6), 5812-5824; https://doi.org/10.3390/cimb46060347 - 11 Jun 2024
Viewed by 344
Abstract
Extracellular vesicles (EVs) have been identified as important mediators for cell-to-cell communication. Citrus-based EVs in particular offer an excellent platform for nutraceutical delivery systems, as their endemic cargo includes micronutrients (e.g., ascorbic acid), which contribute to their antioxidant capacity. Despite being extensively investigated [...] Read more.
Extracellular vesicles (EVs) have been identified as important mediators for cell-to-cell communication. Citrus-based EVs in particular offer an excellent platform for nutraceutical delivery systems, as their endemic cargo includes micronutrients (e.g., ascorbic acid), which contribute to their antioxidant capacity. Despite being extensively investigated as to their therapeutic and diagnostic potential, their cargo is inherently unstable and thus directly affected by their storage and preservation. In this study, EVs were isolated from citrus fruit using tangential flow filtration and evaluated for their physicochemical characteristics, antioxidant activity and effects on human cells. To assess how their isolation and preservation methods affect these properties, the EVs were tested immediately after isolation (from fresh and freeze-thawed juices) or following freeze-drying. A measurable biological effect of cryoprotection on citrus-derived EVs was evident, whether during or after isolation. This was more pronounced in the cell-based assays, ranging from −4% to +32% in human skin fibroblast proliferation. Nevertheless, the effects on human cancer cells varied depending on the cell line. Although these results should be considered preliminary observations, subject to further investigation, it is safe to state that any type of preservation is expected to impact the EVs’ biological activity. Full article
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18 pages, 11668 KiB  
Article
Drug-Resistance Biomarkers in Patient-Derived Colorectal Cancer Organoid and Fibroblast Co-Culture System
by Kyoung-Bin Ryu, Jeong-ah Seo, Kyerim Lee, Juhyun Choi, Geon Yoo, Ji-hye Ha and Mee Ryung Ahn
Curr. Issues Mol. Biol. 2024, 46(6), 5794-5811; https://doi.org/10.3390/cimb46060346 - 11 Jun 2024
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Abstract
Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. [...] Read more.
Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. We used an indirect co-culture system comprising colorectal cancer organoids and cancer-associated fibroblasts to simulate the tumor microenvironment. Immunofluorescence staining validated the characteristics of both organoids and fibroblasts, showing high expression of epithelial cell markers (EPCAM), colon cancer markers (CK20), proliferation markers (KI67), and fibroblast markers (VIM, SMA). Transcriptome profiling was conducted after treatment with anticancer drugs, such as 5-fluorouracil and oxaliplatin, to identify chemoresistance-related genes. Changes in gene expression in the co-cultured colorectal cancer organoids following anticancer drug treatment, compared to monocultured organoids, particularly in pathways related to interferon-alpha/beta signaling and major histocompatibility complex class II protein complex assembly, were identified. These two gene groups potentially mediate drug resistance associated with JAK/STAT signaling. The interaction between colorectal cancer organoids and fibroblasts crucially modulates the expression of genes related to drug resistance. These findings suggest that the interaction between colorectal cancer organoids and fibroblasts significantly influences gene expression related to drug resistance, highlighting potential biomarkers and therapeutic targets for overcoming chemoresistance. Enhanced understanding of the interactions between cancer cells and their microenvironment can lead to advancements in personalized medical research.. Full article
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