Journal Description
Current Issues in Molecular Biology
Current Issues in Molecular Biology
is an international, scientific, peer-reviewed, open access journal on molecular biology, published monthly online by MDPI (from Volume 43 Issue 1-2021).
- 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), PMC, PubMed, Embase, CAPlus / SciFinder, FSTA, AGRIS, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.5 days after submission; acceptance to publication is undertaken in 3.5 days (median values for papers published in this journal in the first half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
Impact Factor:
3.1 (2022);
5-Year Impact Factor:
3.3 (2022)
Latest Articles
Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of Cannabis sativa against Type 2 Diabetes
Curr. Issues Mol. Biol. 2023, 45(9), 7228-7241; https://doi.org/10.3390/cimb45090457 (registering DOI) - 01 Sep 2023
Abstract
The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C.
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The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein–protein and target–compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa’s antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO.
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(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)
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Prokaryotic Expression, Purification, and Antibacterial Activity of the Hepcidin Peptide of Crescent Sweetlips (Plectorhinchus cinctus)
Curr. Issues Mol. Biol. 2023, 45(9), 7212-7227; https://doi.org/10.3390/cimb45090456 (registering DOI) - 31 Aug 2023
Abstract
The hepcidin peptide of crescent sweetlips (Plectorhinchus cinctus) is a cysteine-rich, cationic antimicrobial peptide that plays a crucial role in the innate immune system’s defense against invading microbes. The aim of this study was to identify the optimal parameters for prokaryotic
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The hepcidin peptide of crescent sweetlips (Plectorhinchus cinctus) is a cysteine-rich, cationic antimicrobial peptide that plays a crucial role in the innate immune system’s defense against invading microbes. The aim of this study was to identify the optimal parameters for prokaryotic expression and purification of this hepcidin peptide and characterize its antibacterial activity. The recombinant hepcidin peptides were expressed in Escherichia coli strain Arctic Express (DE3), with culture and induction conditions optimized using response surface methodology (RSM). The obtained hepcidin peptides were then purified before tag cleavage, and their antibacterial activity was determined. The obtained results revealed that induction temperature had the most significant impact on the production of soluble recombinant peptides. The optimum induction conditions were determined to be an isopropylthio-β-galactoside (IPTG) concentration of 0.21 mmol/L, induction temperature of 18.81 °C, and an induction time of 16.01 h. Subsequently, the recombinant hepcidin peptide was successfully purified using Ni-IDA affinity chromatography followed by SUMO protease cleavage. The obtained hepcidin peptide (without His-SUMO tag) demonstrated strong antimicrobial activity in vitro against V. parahaemolyticus, E. coli, and S. aureus. The results showed prokaryotic (E. coli) expression is a feasible way to produce the hepcidin peptide of crescent sweetlips in a cost-effective way, which has great potential to be used as an antimicrobial agent in aquaculture.
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(This article belongs to the Special Issue Advanced Research in Antimicrobial and Antiviral Drugs)
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The Intestinal Microbiome and the Metabolic Syndrome—How Its Manipulation May Affect Metabolic-Associated Fatty Liver Disease (MAFLD)
Curr. Issues Mol. Biol. 2023, 45(9), 7197-7211; https://doi.org/10.3390/cimb45090455 - 31 Aug 2023
Abstract
Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and
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Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and preserving the epithelial barrier function. Disturbances in the IM have been shown to influence the development and progression of MAFLD and play a role in the development of metabolic syndrome (MS). The main treatment for MAFLD involves lifestyle changes, which also influence the IM. Manipulation of the IM by fecal microbial transplantation (FMT) has been approved for the treatment of recurrent Closteroides difficile infection. This may be administered by endoscopic administration from the lower or upper GI tract. Other methods of administration include nasogastric tube, enema, and oral capsules of stool from healthy donors. In this narrative review, we elaborate on the role of the IM in developing MS and MAFLD and on the current experience with IM modulation by FMT on MAFLD.
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(This article belongs to the Topic Clinical, Translational and Basic Research on Liver Diseases, 2nd Volume)
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Six Express Sequence Tag–Simple Sequence Repeat Primers Reveal Genetic Diversity in the Cultivars of Three Zanthoxylum Species
Curr. Issues Mol. Biol. 2023, 45(9), 7183-7196; https://doi.org/10.3390/cimb45090454 - 30 Aug 2023
Abstract
Zanthoxylum (Sichuan pepper), with its rich cultivars, has long been widely cultivated in China for its unique seasoning and medicinal uses, but most of its cultivars have similar morphological characteristics. Therefore, we hypothesized that the genetic diversity of Zanthoxylum cultivars is low because
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Zanthoxylum (Sichuan pepper), with its rich cultivars, has long been widely cultivated in China for its unique seasoning and medicinal uses, but most of its cultivars have similar morphological characteristics. Therefore, we hypothesized that the genetic diversity of Zanthoxylum cultivars is low because of their apomixis and long cultivation history. In this study, we aimed to investigate the genetic diversity of three Zanthoxylum species on the cultivar level based on express sequence tag–simple sequence repeat (EST-SSR) primers. In total, 121 samples of three Zanthoxylum species (Z. bungeanum, Z. armatum and Z. piperitum) were collected from different areas in China for genetic diversity analysis. A total of six specificity and polymorphism EST-SSR primers, which we selected from among 120 primers based on two transcriptomes (Z. bungeanum, Z. armatum) in our earlier study, were used to evaluate genetic diversity based on capillary electrophoresis technology. The results of our analysis using the unweighted pair group method with arithmetic mean (UPGMA) indicated that most of the samples are clustered in one clade in the UPGMA dendrogram, and the average genetic distance was 0.6409. Principal component analysis (PCA) showed that Z. piperitum may have a closer genetic relationship with Z. bungeanum than with Z. armatum. An analysis of molecular variation (AMOVA) showed that the genetic variation mainly stemmed from individuals within populations; the genetic differentiation coefficient (PhiPT) was 0.429, the gene flow (Nm) between populations was 0.333, and the differences among populations were not significant (p > 0.001). For the intraspecific populations of ZB, the percentage of genetic variation was 53% among populations and 47% within populations, with non-significant differences between populations (p > 0.001). The genetic differentiation coefficient (PhiT) was 0.529, and the gene flow (Nm) was 0.223. For the intraspecific populations of ZA, the results indicated that the percentage of genetic variation was 29% among populations and 71% within populations, with non-significant differences between populations (p > 0.001); the genetic differentiation coefficient (PhiPT) was 0.293, and the gene flow (Nm) was 0.223. Through genetic structure analysis (GSA), we predicted that these 121 samples belonged to two optimal subgroups, which means that all the samples probably originated from two gene pools. Above all, this indicated that the genetic diversity of the 121 Zanthoxylum samples was relatively low at both the species and cultivar levels, a finding which was consistent with our initial assumptions. This study provides a reference, with molecular-level data, for the further identification of Zanthoxylum species.
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(This article belongs to the Section Molecular Plant Sciences)
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Pathological Effects of SARS-CoV-2 Associated with Hematological Abnormalities
Curr. Issues Mol. Biol. 2023, 45(9), 7161-7182; https://doi.org/10.3390/cimb45090453 - 28 Aug 2023
Abstract
The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has claimed the lives of 6.9 million people and infected over 765 million. It has become a major worldwide health problem and is also known to
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The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has claimed the lives of 6.9 million people and infected over 765 million. It has become a major worldwide health problem and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower respiratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse outcomes. Prophylactic anticoagulation is essential to prevent complications and death rates associated with the virus’s effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation (DIC) exhibits some similarities to DIC induced by sepsis. Lactate dehydrogenase (LDH), D-dimer, ferritin, and C-reactive protein (CRP) biomarkers often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.
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(This article belongs to the Special Issue Tailored Molecular and Pathophysiological Approach to COVID-19: Ambition and Need)
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Mouse Model of Anti-Obesity Effects of Blautia hansenii on Diet-Induced Obesity
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, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7147-7160; https://doi.org/10.3390/cimb45090452 - 26 Aug 2023
Abstract
Reportedly, a relationship exists between intestinal microflora and obesity-related lifestyle diseases. Blautia spp. a major intestinal microbiota, accounts for 3–11% of human intestinal microflora. Epidemiological reports have described that people with more visceral fat have less Blautia hansenii in their intestinal tract irrespective of
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Reportedly, a relationship exists between intestinal microflora and obesity-related lifestyle diseases. Blautia spp. a major intestinal microbiota, accounts for 3–11% of human intestinal microflora. Epidemiological reports have described that people with more visceral fat have less Blautia hansenii in their intestinal tract irrespective of age or gender. However, the effect of oral administration of heat-sterilized Blautia hansenii on obesity has not been clarified. Therefore, the aim of this study was to evaluate the effects of dietary Blautia hansenii administration on obesity in high-fat-diet-induced obesity in a mouse model. Heat-sterilized cells of Blautia hansenii were used. C57BL/6J mice (normal mice, n = 7) were fed with each experimental diet for nine weeks. Diets for experimentation were: normal-fat (NF) diets, high-fat (HF) diets, and high-fat + Blautia hansenii (HF + Blautia) diets. The HF + Blautia group was administered about 1 × 109 (CFU/mouse/day) of Blautia hansenii. During the periods of experimentation, body weight, food intake, water consumption, and fecal weight were recorded, and glucose tolerance tests were performed. Subsequently, the white adipose tissue (WAT) weight and serum components were measured. Short-chain fatty acid contents in the feces and cecum were analyzed. Furthermore, changes in the intestinal microflora were analyzed using meta-genomics analysis. Results showed that the total weight of WAT in the HF + Blautia group was significantly lower (13.2%) than that of the HF group. Moreover, the HF + Blautia group exhibited better glucose tolerance than the HF group. Productivity of short-chain fatty acids in the intestinal tract was at a significantly (p < 0.05) low level in the HF group; on the other hand, it recovered in the HF + Blautia group. Furthermore, there was a higher ratio of Blautia (p < 0.05) in the intestinal tracts of the HF + Blautia group than in the HF group. These results suggest that Blautia hansenii administration suppresses obesity induced by a high-fat diet.
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(This article belongs to the Special Issue Metabolic Interactions between the Gut Microbiome and Organism)
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Mutual Modulation of the Activities of Human CYP2D6 and Four UGTs during the Metabolism of Propranolol
Curr. Issues Mol. Biol. 2023, 45(9), 7130-7146; https://doi.org/10.3390/cimb45090451 - 26 Aug 2023
Abstract
Cytochromes P450 (CYP) and UDP-glucuronosyltransferases (UGT) are two enzyme families that play an important role in drug metabolism, catalyzing either the functionalization or glucuronidation of xenobiotics. However, their mutual interactions are poorly understood. In this study, the functional interactions of human CYP2D6 with
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Cytochromes P450 (CYP) and UDP-glucuronosyltransferases (UGT) are two enzyme families that play an important role in drug metabolism, catalyzing either the functionalization or glucuronidation of xenobiotics. However, their mutual interactions are poorly understood. In this study, the functional interactions of human CYP2D6 with four human UGTs (UGT1A7, UGT1A8, UGT1A9, and UGT2A1) were investigated using our previously established co-expression model system in the fission yeast Schizosaccharomyces pombe. The substrate employed was propranolol because it is well metabolized by CYP2D6. Moreover, the CYP2D6 metabolite 4-hydroxypropranolol is a known substrate for the four UGTs included in this study. Co-expression of either UGT1A7, UGT1A8, or UGT1A9 was found to increase the activity of CYP2D6 by a factor of 3.3, 2.1 or 2.8, respectively, for the conversion of propranolol to 4-hydroxypropranolol. In contrast, UGT2A1 co-expression did not change CYP2D6 activity. On the other hand, the activities of all four UGTs were completely suppressed by co-expression of CYP2D6. This data corroborates our previous report that CYP2D6 is involved in functional CYP-UGT interactions and suggest that such interactions can contribute to both adverse drug reactions and changes in drug efficacy.
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(This article belongs to the Special Issue Recent Advances in Cytochrome P450 (CYP))
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QTL Mapping and Genome-Wide Association Study Reveal Genetic Loci and Candidate Genes Related to Soluble Solids Content in Melon
Curr. Issues Mol. Biol. 2023, 45(9), 7110-7129; https://doi.org/10.3390/cimb45090450 - 26 Aug 2023
Abstract
Melon (Cucumis melo L.) is an economically important Cucurbitaceae crop grown around the globe. The sweetness of melon is a significant factor in fruit quality and consumer appeal, and the soluble solids content (SSC) is a key index of melon sweetness. In
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Melon (Cucumis melo L.) is an economically important Cucurbitaceae crop grown around the globe. The sweetness of melon is a significant factor in fruit quality and consumer appeal, and the soluble solids content (SSC) is a key index of melon sweetness. In this study, 146 recombinant inbred lines (RILs) derived from two oriental melon materials with different levels of sweetness containing 1427 bin markers, and 213 melon accessions containing 1,681,775 single nucleotide polymorphism (SNP) markers were used to identify genomic regions influencing SSC. Linkage mapping detected 10 quantitative trait loci (QTLs) distributed on six chromosomes, seven of which were overlapped with the reported QTLs. A total of 211 significant SNPs were identified by genome-wide association study (GWAS), 138 of which overlapped with the reported QTLs. Two new stable, co-localized regions on chromosome 3 were identified by QTL mapping and GWAS across multiple environments, which explained large phenotypic variance. Five candidate genes related to SSC were identified by QTL mapping, GWAS, and qRT-PCR, two of which were involved in hydrolysis of raffinose and sucrose located in the new stable loci. The other three candidate genes were involved in raffinose synthesis, sugar transport, and production of substrate for sugar synthesis. The genomic regions and candidate genes will be helpful for molecular breeding programs and elucidating the mechanisms of sugar accumulation.
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(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants)
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Axonal Protection by Oral Nicotinamide Riboside Treatment with Upregulated AMPK Phosphorylation in a Rat Glaucomatous Degeneration Model
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, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7097-7109; https://doi.org/10.3390/cimb45090449 - 25 Aug 2023
Abstract
Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), has been studied to support human health against metabolic stress, cardiovascular disease, and neurodegenerative disease. In the present study, we investigated the effects of oral NR on axonal damage in a
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Nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), has been studied to support human health against metabolic stress, cardiovascular disease, and neurodegenerative disease. In the present study, we investigated the effects of oral NR on axonal damage in a rat ocular hypertension model. Intraocular pressure (IOP) elevation was induced by laser irradiation and then the rats received oral NR of 1000 mg/kg/day daily. IOP elevation was seen 7, 14, and 21 days after laser irradiation compared with the controls. We confirmed that oral NR administration significantly increased NAD+ levels in the retina. After 3-week oral administration of NR, morphometric analysis of optic nerve cross-sections showed that the number of axons was protected compared with that in the untreated ocular hypertension group. Oral NR administration significantly prevented retinal ganglion cell (RGC) fiber loss in retinal flat mounts, as shown by neurofilament immunostaining. Immunoblotting samples from the optic nerves showed that oral NR administration augmented the phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) level in rats with and without ocular hypertension induction. Immunohistochemical analysis showed that some p-AMPK-immunopositive fibers were colocalized with neurofilament immunoreactivity in the control group, and oral NR administration enhanced p-AMPK immunopositivity. Our findings suggest that oral NR administration protects against glaucomatous RGC axonal degeneration with the possible upregulation of p-AMPK.
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(This article belongs to the Topic Animal Models of Human Disease)
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A Fermented Wheat Germ Extract Contains Protein Components Active against NSCLC Xenografts In Vivo
Curr. Issues Mol. Biol. 2023, 45(9), 7087-7096; https://doi.org/10.3390/cimb45090448 - 25 Aug 2023
Abstract
Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due to toxicity. Thus, the
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Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due to toxicity. Thus, the need remains for non-toxic, effective NSCLC therapies, especially in an elderly patient population. Our lab has previously identified a protein fraction from the nutraceutical Avemar®—dubbed fermented wheat germ protein (FWGP)—with demonstrated efficacy in lymphoma models both in vitro and in vivo. Here, we show that FWGP also has anti-tumor activity in vitro and in vivo against lung cancer. In vitro cytotoxicity against multiple lung cancer cell lines yielded IC50 values comparable to those previously established with the parent product, Avemar. Further, significant A549 xenograft growth inhibition occurred in athymic nu/nu mice receiving FWGP in both pre-radiated and non-radiated models when compared to the untreated control. Encouragingly, mice treated with FWGP experienced no toxicities as detected by weight reduction or blood chemistry analysis. These data support the further study of FWGP as a potential non-toxic therapy for lung cancer and other oncologic indications.
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(This article belongs to the Special Issue Protein Hydrolysates: Biological Activity and Applications)
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Long Noncoding RNA TALAM1 Is a Transcriptional Target of the RUNX2 Transcription Factor in Lung Adenocarcinoma
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, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7075-7086; https://doi.org/10.3390/cimb45090447 - 24 Aug 2023
Abstract
Background: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development
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Background: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal–epithelial transition processes. In this paper, we identified TALAM1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings. Methods: We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF. In addition, we performed shRNA-mediated knockdown of RUNX2 in this lung adenocarcinoma cell line to confirm the regulatory role of RUNX2 in TALAM1 expression. Results: We observed RUNX2 overexpression in cell lines and primary cultured lung cancer cells. Interestingly, we found that lncRNA TALAM1 was a target of RUNX2 and that RUNX2 exerted a negative regulatory effect on TALAM1 transcription.
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(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)
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Targeting FAK/PYK2 with SJP1602 for Anti-Tumor Activity in Triple-Negative Breast Cancer
Curr. Issues Mol. Biol. 2023, 45(9), 7058-7074; https://doi.org/10.3390/cimb45090446 - 24 Aug 2023
Abstract
Triple-negative breast cancer (TNBC) presents significant challenges due to its aggressive nature and limited treatment options. Focal adhesion kinase (FAK) has emerged as a critical factor promoting tumor growth and metastasis in TNBC. Despite encouraging results from preclinical and early clinical trials with
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Triple-negative breast cancer (TNBC) presents significant challenges due to its aggressive nature and limited treatment options. Focal adhesion kinase (FAK) has emerged as a critical factor promoting tumor growth and metastasis in TNBC. Despite encouraging results from preclinical and early clinical trials with various FAK inhibitors, none have yet achieved clinical success in TNBC treatment. This study investigates the therapeutic potential of a novel dual inhibitor of FAK and PYK2, named SJP1602, for TNBC. In vitro experiments demonstrate that SJP1602 effectively inhibits FAK and PYK2 activities, showing potent effects on both kinases. SJP1602 shows concentration-dependent inhibition of cell growth, migration, invasion, and 3D spheroid formation in TNBC cell lines, surpassing the efficacy of other FAK inhibitors. Pharmacokinetic studies in rats indicate favorable bioavailability and sustained plasma concentrations of SJP1602, supporting its potential as a therapeutic agent. Furthermore, in TNBC xenograft models, SJP1602 exhibits significant dose-dependent inhibition of tumor growth. These promising results emphasize the potential of SJP1602 as a potent dual inhibitor of FAK and PYK2, deserving further investigation in clinical trials for TNBC treatment.
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(This article belongs to the Section Molecular Medicine)
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Targeted Expression to Liver of an antimiR-33 Sponge as a Gene Therapy Strategy against Hypercholesterolemia: In Vitro Study
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, , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 7043-7057; https://doi.org/10.3390/cimb45090445 - 24 Aug 2023
Abstract
Atherosclerosis is the leading cause of cardiovascular diseases in Mexico and worldwide. The membrane transporters ABCA1 and ABCG1 are involved in the reverse transport of cholesterol and stimulate the HDL synthesis in hepatocytes, therefore the deficiency of these transporters promotes the acceleration of
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Atherosclerosis is the leading cause of cardiovascular diseases in Mexico and worldwide. The membrane transporters ABCA1 and ABCG1 are involved in the reverse transport of cholesterol and stimulate the HDL synthesis in hepatocytes, therefore the deficiency of these transporters promotes the acceleration of atherosclerosis. MicroRNA-33 (miR-33) plays an important role in lipid metabolism and exerts a negative regulation on the transporters ABCA1 and ABCG1. It is known that by inhibiting the function of miR-33 with antisense RNA, HDL levels increase and atherogenic risk decreases. Therefore, in this work, a genetic construct, pPEPCK-antimiR-33-IRES2-EGFP, containing a specific antimiR-33 sponge with two binding sites for miR-33 governed under the PEPCK promoter was designed, constructed, and characterized, the identity of which was confirmed by enzymatic restriction, PCR, and sequencing. Hep G2 and Hek 293 FT cell lines, as well as a mouse hepatocyte primary cell culture were transfected with this plasmid construction showing expression specificity of the PEPCK promoter in hepatic cells. An analysis of the relative expression of miR-33 target messengers showed that the antimiR-33 sponge indirectly induces the expression of its target messengers (ABCA1 and ABCG1). This strategy could open new specific therapeutic options for hypercholesterolemia and atherosclerosis, by blocking the miR-33 specifically in hepatocytes.
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(This article belongs to the Special Issue A Focus on Molecular Basis in Cardiac Diseases)
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Eupatilin Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Mice
Curr. Issues Mol. Biol. 2023, 45(9), 7027-7042; https://doi.org/10.3390/cimb45090444 - 23 Aug 2023
Abstract
Acute kidney injury (AKI) is a common complication of sepsis. Eupatilin (EUP) is a natural flavone with multiple biological activities and has beneficial effects against various inflammatory disorders. However, whether EUP has a favorable effect on septic AKI remains unknown. Here, we examined
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Acute kidney injury (AKI) is a common complication of sepsis. Eupatilin (EUP) is a natural flavone with multiple biological activities and has beneficial effects against various inflammatory disorders. However, whether EUP has a favorable effect on septic AKI remains unknown. Here, we examined the effect of EUP on lipopolysaccharide (LPS)-evoked AKI in mice. LPS-evoked renal dysfunction was attenuated by EUP, as reflected by reductions in serum creatinine and blood urea nitrogen levels. LPS injection also induced structural damage such as tubular cell detachment, tubular dilatation, brush border loss of proximal tubules, and upregulation of tubular injury markers. However, EUP significantly ameliorated this structural damage. EUP decreased serum and renal cytokine levels, prevented macrophage infiltration, and inhibited mitogen-activated protein kinase and NF-κB signaling cascades. Lipid peroxidation and DNA oxidation were increased after LPS treatment. However, EUP mitigated LPS-evoked oxidative stress through downregulation of NPDPH oxidase 4 and upregulation of antioxidant enzymes. EUP also inhibited p53-mediated apoptosis in LPS-treated mice. Therefore, these results suggest that EUP ameliorates LPS-evoked AKI through inhibiting inflammation, oxidative stress, and apoptosis.
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(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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HSP90 Inhibitor PU-H71 in Combination with BH3-Mimetics in the Treatment of Acute Myeloid Leukemia
Curr. Issues Mol. Biol. 2023, 45(9), 7011-7026; https://doi.org/10.3390/cimb45090443 - 23 Aug 2023
Abstract
Targeting the molecular chaperone HSP90 and the anti-apoptotic proteins MCL1 and BCL2 may be a promising novel approach in the treatment of acute myeloid leukemia (AML). The HSP90 inhibitor PU-H71, MCL1 inhibitor S63845, and BCL2 inhibitor venetoclax were assessed as single agents and
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Targeting the molecular chaperone HSP90 and the anti-apoptotic proteins MCL1 and BCL2 may be a promising novel approach in the treatment of acute myeloid leukemia (AML). The HSP90 inhibitor PU-H71, MCL1 inhibitor S63845, and BCL2 inhibitor venetoclax were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells. AML cells represented all major morphologic and molecular subtypes including FLT3-ITD and TP53 mutant AML cell lines and a variety of patient-derived AML cells. Results: PU-H71 and combination treatments with MCL1 inhibitor S63845 or BCL2 inhibitor venetoclax induced cell cycle arrest and apoptosis in susceptible AML cell lines and primary AML. The majority of the primary AML samples were responsive to PU-H71 in combination with BH3 mimetics. Elevated susceptibility to PU-H71 and S63845 was associated with FLT3 mutated AML with CD34 < 20%. Elevated susceptibility to PU-H71 and venetoclax was associated with primary AML with CD117 > 80% and CD11b < 45%. The combination of HSP90 inhibitor PU-H71 and MCL1 inhibitor S63845 may be a candidate treatment for FLT3-mutated AML with moderate CD34 positivity while the combination of HSP90 inhibitor PU-H71 and BCL2 inhibitor venetoclax may be more effective in the treatment of primitive AML with high CD117 and low CD11b positivity.
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(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer, 2nd Edition)
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The Chemosensing Role of CatSper in Mammalian Sperm: An Updated Review
Curr. Issues Mol. Biol. 2023, 45(9), 6995-7010; https://doi.org/10.3390/cimb45090442 - 23 Aug 2023
Abstract
After sperm enter the female reproductive tract, the physicochemical and biochemical microenvironment undergoes significant changes. In particular, the large changes in various ions encountered by sperm may alter the physiology of sperm, ultimately compromising capacitation and fertilization. Thus, the rapid response to environmental
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After sperm enter the female reproductive tract, the physicochemical and biochemical microenvironment undergoes significant changes. In particular, the large changes in various ions encountered by sperm may alter the physiology of sperm, ultimately compromising capacitation and fertilization. Thus, the rapid response to environmental variations is vital for sperm functions. For example, Calcium, the most crucial ion for sperm functions, enters into sperm via Ca2+ permeable ion channels. The cation channel of sperm (CatSper) is a sperm-specific, pH-sensitive, and Ca2+-permeable ion channel. It is responsible for the predominant Ca2+ entry in mammalian sperm and is involved in nearly every event of sperm to acquire fertilizing capability. In addition, CatSper also serves as a pivotal polymodal chemosensor in mammalian sperm by responding to multiple chemical cues. Physiological chemicals (such as progesterone, prostaglandins, β-defensins, and odorants) provoke Ca2+ entry into sperm by activating CatSper and thus triggering sperm functions. Additionally, synthetic and natural chemicals (such as medicines, endocrine disrupting chemicals, drugs of abuse, and antioxidants) affect sperm functions by regulating CatSper-dependent Ca2+ signaling. Therefore, understanding the interactions between CatSper and extracellular ligands sheds light on the mechanisms underlying male infertility and offers innovative diagnostic and treatment approaches. This underscores the importance of CatSper as a crucial regulatory target in male reproduction, linking sperm function with the extracellular environment. In conclusion, this review comprehensively summarizes the relevant studies describing the environmental factors that affect CatSper in humans and rodents.
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(This article belongs to the Special Issue Molecular Research in Reproductive Biology)
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Open AccessCommunication
Dose Rate Effect on Cell Survival in BNCT
Curr. Issues Mol. Biol. 2023, 45(9), 6986-6994; https://doi.org/10.3390/cimb45090441 - 23 Aug 2023
Abstract
The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%.
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The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%. However, the necessity of maintaining a constant beam dose rate has not been fully discussed. We therefore clarified the effect of different physical dose rates of the accelerator BNCT on biological effects. SAS and A172 cells exposed to 10B-boronophenylalanine were irradiated using a neutron beam (normal operating current, 100 μA) at the Aomori Quantum Science Center. Thermal neutron flux was attenuated to 50.0 ± 0.96% under 50 μA irradiation compared to that under 100 μA irradiation. Cells were given physical doses of 1.67 and 3.36 Gy at 30 and 60 mC, respectively, and survival was significantly increased after 50 μA irradiation for both cell types (p = 0.0052 for SAS; p = 0.046 for A172, for 60 mC). Differences in accelerator BNCT beam dose rates have non-negligible effects on biological effects. Dose rate fluctuations and differences should not be easily permitted to obtain consistent biological effects.
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(This article belongs to the Special Issue Understanding Cellular Radiation Responses for Radiation Therapy)
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Open AccessArticle
Immunomodulatory and Antioxidant Properties of Ipomoea batatas Flour and Extracts Obtained by Green Extraction
by
, , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 6967-6985; https://doi.org/10.3390/cimb45090440 - 22 Aug 2023
Abstract
Sweet potato (SP), Ipomoea batatas Lam, belongs to the Convolvulaceae family. It produces edible storage roots. Currently, orange varieties contribute to improving food systems and managing vitamin A deficiency. Processing of this food crop into flour allows better conservation. However, nutrition health data
[...] Read more.
Sweet potato (SP), Ipomoea batatas Lam, belongs to the Convolvulaceae family. It produces edible storage roots. Currently, orange varieties contribute to improving food systems and managing vitamin A deficiency. Processing of this food crop into flour allows better conservation. However, nutrition health data regarding SP flour obtained by green extraction remains scarce. In this study, we therefore explored its phytochemistry and its associated bioactivity potential for human health. We analyzed the nutritional composition of orange flesh sweet potato (OFSP) flour and assessed the antioxidant (free radical scavenging) and immunomodulatory (on inflammatory murine macrophages) properties of the extract. More specifically, we measured the impact of OFSP flour extract on mediators such as Nitric Oxide (NO) and the production of pro-inflammatory cytokines such as Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-alpha), Monocyte Chemoattractant Protein-1 (MCP-1), and Prostaglandin-E2 (PGE-2). Our results indicated significant fiber, mineral, beta-carotene, and polyphenols content in the extracts, and antioxidant and immunomodulatory bioactivities were also demonstrated with a concentration-dependent inhibition of cytokine production. Taken together, our results suggest that Ipomoea batatas flour could, in addition to being a good source of energy and beta-carotene provitamin A, constitute a food of interest for the prophylaxis of metabolic diseases associated with an underlying low-grade inflammatory state.
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(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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Open AccessCase Report
Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with Haemophilus influenzae Meningitis in a Newborn
by
, , , , , , , , , , , , , and
Curr. Issues Mol. Biol. 2023, 45(9), 6958-6966; https://doi.org/10.3390/cimb45090439 - 22 Aug 2023
Abstract
Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact
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Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology.
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(This article belongs to the Special Issue Human and Animal Infectious Diseases: Prevention, Diagnosis, and Treatment)
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Open AccessArticle
Involvement of Glycogen Synthase Kinase 3β (GSK3β) in Formation of Phosphorylated Tau and Death of Retinal Ganglion Cells of Rats Caused by Optic Nerve Crush
Curr. Issues Mol. Biol. 2023, 45(9), 6941-6957; https://doi.org/10.3390/cimb45090438 - 22 Aug 2023
Abstract
Tauopathy is a neurodegenerative condition associated with oligomeric tau formation through abnormal phosphorylation. We previously showed that tauopathy is involved in death of retinal ganglion cells (RGCs) after optic nerve crush (ONC). It has been proposed that glycogen synthase kinase 3β (GSK3β) is
[...] Read more.
Tauopathy is a neurodegenerative condition associated with oligomeric tau formation through abnormal phosphorylation. We previously showed that tauopathy is involved in death of retinal ganglion cells (RGCs) after optic nerve crush (ONC). It has been proposed that glycogen synthase kinase 3β (GSK3β) is involved in the hyperphosphorylation of tau in Alzheimer’s disease. To determine the roles of GSK3β in tauopathy-related death of RGCs, lithium chloride (LiCl), a GSK3β inhibitor, was injected intravitreally just after ONC. The neuroprotective effects of LiCl were determined by counting Tuj-1-stained RGCs on day 7. Changes of phosphorylated (ser 396) tau in the retina were determined by Simple Western analysis (WES) on day 3. Retinal GSK3β levels were determined by immunohistochemistry (IHC) and an ELISA. There was a 1.9- and 2.1-fold increase in the levels of phosphorylated tau monomers and dimers on day 3 after ONC. LiCl significantly suppressed the increase in the levels of phosphorylated tau induced by ONC. GSK3β was mainly present in somas of RGCs, and ELISA showed that retinal levels increased to 2.0-fold on day 7. IHC showed that the GSK3β expression increased over time and remained in RGCs that were poorly stained by Tuj-1. The GSK3β and tau expression was colocalized in RGCs. The number of RGCs decreased from 1881 ± 188 (sham control) to 1150 ± 192 cells/mm2 on day 7, and LiCl preserved the levels at 1548 ± 173 cells/mm2. Accordingly, GSK3β may be a promising target for some optic nerve injuries.
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(This article belongs to the Special Issue Neuropathology: From Molecular Mechanisms to Therapeutic Solutions)
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