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 13.5 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names are published annually in the journal.
Impact Factor:
3.1 (2022);
5-Year Impact Factor:
3.3 (2022)
Latest Articles
Norcantharidin Enhances the Antitumor Effect of 5-Fluorouracil by Inducing Apoptosis of Cervical Cancer Cells: Network Pharmacology, Molecular Docking, and Experimental Validation
Curr. Issues Mol. Biol. 2024, 46(5), 3906-3918; https://doi.org/10.3390/cimb46050242 (registering DOI) - 25 Apr 2024
Abstract
The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated
[...] Read more.
The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.
Full article
(This article belongs to the Section Molecular Pharmacology)
►
Show Figures
Open AccessReview
The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease
by
Minela Aida Maranduca, Cristian Tudor Cozma, Andreea Clim, Alin Constantin Pinzariu, Ionut Tudorancea, Irene Paula Popa, Cristina Iuliana Lazar, Roxana Moscalu, Nina Filip, Mihaela Moscalu, Mihai Constantin, Dragos Viorel Scripcariu, Dragomir Nicolae Serban and Ionela Lacramioara Serban
Curr. Issues Mol. Biol. 2024, 46(5), 3877-3905; https://doi.org/10.3390/cimb46050241 (registering DOI) - 25 Apr 2024
Abstract
Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone–Vitamin D–Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in
[...] Read more.
Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone–Vitamin D–Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated “trade-off hypothesis” reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient’s prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin–Angiotensin–Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.
Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
►▼
Show Figures
Figure 1
Open AccessArticle
Network Meta-Analysis: Effect of Cold Stress on the Gene Expression of Swine Adipocytes ATGL, CIDEA, UCP2, and UCP3
by
Zhenhua Guo, Lei Lv, Di Liu, Hong Ma, Liang Wang, Bo Fu and Fang Wang
Curr. Issues Mol. Biol. 2024, 46(5), 3866-3876; https://doi.org/10.3390/cimb46050240 (registering DOI) - 25 Apr 2024
Abstract
Cold stress significantly affects gene expression in adipocytes; studying this phenomenon can help reveal the pathogeneses of conditions such as obesity and insulin resistance. Adipocyte triglyceride lipase (ATGL); cell death-inducing deoxyribonucleic acid (DNA) fragmentation factor subunit alpha (DFFA)-like effector (CIDEA
[...] Read more.
Cold stress significantly affects gene expression in adipocytes; studying this phenomenon can help reveal the pathogeneses of conditions such as obesity and insulin resistance. Adipocyte triglyceride lipase (ATGL); cell death-inducing deoxyribonucleic acid (DNA) fragmentation factor subunit alpha (DFFA)-like effector (CIDEA); and uncoupling protein genes UCP1, UCP2, and UCP3 are the most studied genes in pig adipose tissues under cold stress. However, contradictory results have been observed in gene expression changes to UCP3 and UCP2 when adipose tissues under cold stress were examined. Therefore, we conducted a meta-analysis of 32 publications in total on the effect of cold stress on the expression of ATGL, CIDEA, UCP2, and UCP3. Our results showed that cold stress affected the expression of swine adipocyte genes; specifically, it was positively correlated with the expression of UCP3 in swine adipocytes. Conversely, expression of ATGL was negatively affected under cold stress conditions. In addition, the loss of functional UCP1 in pigs likely triggered a compensatory increase in UCP3 activity. We also simulated the docking results of UCP2 and UCP3. Our results showed that UCP2 could strongly bind to adenosine triphosphate (ATP), meaning that UCP3 played a more significant role in pig adipocytes.
Full article
(This article belongs to the Special Issue Lipid Metabolism in Obesity)
►▼
Show Figures
Figure 1
Open AccessArticle
Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer
by
Miguel A. Ortega, Laura Jiménez-Álvarez, Oscar Fraile-Martinez, Cielo Garcia-Montero, Luis G. Guijarro, Leonel Pekarek, Silvestra Barrena-Blázquez, Ángel Asúnsolo, Laura López-González, María Del Val Toledo-Lobo, Melchor Álvarez-Mon, Miguel A. Saez, Alberto Gutiérrez-Calvo and Raúl Díaz-Pedrero
Curr. Issues Mol. Biol. 2024, 46(5), 3839-3865; https://doi.org/10.3390/cimb46050239 (registering DOI) - 25 Apr 2024
Abstract
Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use
[...] Read more.
Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan–Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC’s pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.
Full article
(This article belongs to the Special Issue Molecular Advances in Cancer and the Tumor Microenvironment)
►▼
Show Figures
Figure 1
Open AccessReview
Actinomycetes Associated with Arthropods as a Source of New Bioactive Compounds
by
Carlos Olano and Miriam Rodríguez
Curr. Issues Mol. Biol. 2024, 46(5), 3822-3838; https://doi.org/10.3390/cimb46050238 - 24 Apr 2024
Abstract
Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the
[...] Read more.
Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the drug industry pipeline. Different strategies have been pursued to increase the chances of discovering new molecules, such as studying underexplored environments like arthropod symbionts, which represent a relevant reservoir for active metabolites. This review summarizes recent research on the identification of bioactive molecules produced by Actinomycetes associated with arthropods’ microbiome. The metabolites have been categorized based on their structural properties and host, highlighting that multidisciplinary approaches will be the key to fully understanding this complex relationship.
Full article
(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)
►▼
Show Figures
Figure 1
Open AccessCommunication
Meat-Borne-Parasite: A Nanopore-Based Meta-Barcoding Work-Flow for Parasitic Microbiodiversity Assessment in the Wild Fauna of French Guiana
by
Adria Matoute, Simone Maestri, Mona Saout, Laure Laghoe, Stéphane Simon, Hélène Blanquart, Miguel Angel Hernandez Martinez and Magalie Pierre Demar
Curr. Issues Mol. Biol. 2024, 46(5), 3810-3821; https://doi.org/10.3390/cimb46050237 - 24 Apr 2024
Abstract
French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there has been limited data available on the description of parasites circulating in this area, especially on protozoan
[...] Read more.
French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there has been limited data available on the description of parasites circulating in this area, especially on protozoan belonging to the phylum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on the Oxford Nanopore Technologies sequencing platform using the 18S gene of 14 Apicomplexa positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify 10 samples out of 14 as Apicomplexa positive and reveal the presence of co-carriages. The same samples were also sequenced with the Illumina platform for validation purposes. For samples identified as Apicomplexa positive by both platforms, a strong positive correlation at up to the genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detection, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.
Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
►▼
Show Figures
Figure 1
Open AccessReview
Insights into the Molecular Mechanism of Endothelial Glycocalyx Dysfunction during Heart Surgery
by
Antea Kršek, Lara Batičić, Božena Ćurko-Cofek, Tanja Batinac, Gordana Laškarin, Silvija Miletić-Gršković and Vlatka Sotošek
Curr. Issues Mol. Biol. 2024, 46(5), 3794-3809; https://doi.org/10.3390/cimb46050236 - 23 Apr 2024
Abstract
The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its main function is to participate in separating the circulating blood from the inner layers of the vessels
[...] Read more.
The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its main function is to participate in separating the circulating blood from the inner layers of the vessels and the surrounding tissues. Physiologically, the EGC stimulates mechanotransduction, the endothelial charge, thrombocyte adhesion, leukocyte tissue recruitment, and molecule extravasation. Hence, severe impairment of the EGC has been implicated in various pathological conditions, including sepsis, diabetes, chronic kidney disease, inflammatory disorders, hypernatremia, hypervolemia, atherosclerosis, and ischemia/reperfusion injury. Moreover, alterations in EGC have been associated with altered responses to therapeutic interventions in conditions such as cardiovascular diseases. Investigation into the function of the glycocalyx has expanded knowledge about vascular disorders and indicated the need to consider new approaches in the treatment of severe endothelial dysfunction. This review aims to present the current understanding of the molecular mechanisms underlying cardiovascular diseases and to elucidate the impact of heart surgery on EGC dysfunction.
Full article
(This article belongs to the Special Issue Focus on Molecular Basis of Cardiac Diseases)
►▼
Show Figures
Figure 1
Open AccessArticle
Açaí (Euterpe oleracea Mart.) Seed Oil and Its Nanoemulsion: Chemical Characterisation, Toxicity Evaluation, Antioxidant and Anticancer Activities
by
Katia Regina Assunção Borges, Lais Araújo Souza Wolff, Marcos Antonio Custódio Neto da Silva, Allysson Kayron de Carvalho Silva, Carmem Duarte Lima Campos, Franscristhiany Silva Souza, Amanda Mara Teles, André Álvares Marques Vale, Henrique Pascoa, Eliana Martins Lima, Eduardo Martins de Sousa, Ana Clara Silva Nunes, Rui M. Gil da Costa, Ana Isabel Faustino-Rocha, Rafael Cardoso Carvalho and Maria do Desterro Soares Brandão Nascimento
Curr. Issues Mol. Biol. 2024, 46(5), 3763-3793; https://doi.org/10.3390/cimb46050235 - 23 Apr 2024
Abstract
This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical
[...] Read more.
This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical cancer cell lines, alongside assessing its antioxidant and toxicity properties both in vitro and in vivo. Extracted from fruits sourced in Brazil, the oil underwent thorough chemical characterization using gas chromatography–mass spectrometry. The resulting nanoemulsion was prepared and evaluated for stability, particle size, and antioxidant properties. The nanoemulsion exhibited translucency, fluidity, and stability post centrifugation and temperature tests, with a droplet size of 238.37, PDI -9.59, pH 7, and turbidity 0.267. In vitro assessments on cervical cancer cell lines revealed antitumour effects, including inhibition of cell proliferation, migration, and colony formation. Toxicity tests conducted in cell cultures and female Swiss mice demonstrated no adverse effects of both açaí seed oil and nanoemulsion. Overall, açaí seed oil, particularly when formulated into a nanoemulsion, presents potential for cancer treatment due to its bioactive properties and safety profile.
Full article
(This article belongs to the Section Molecular Pharmacology)
►▼
Show Figures
Figure 1
Open AccessArticle
Optimizing Embryo Collection for Application of CRISPR/Cas9 System and Generation of Fukutin Knockout Rat Using This Method
by
Dong-Won Seol, Byoung-Jin Park, Deog-Bon Koo, Ji-Su Kim, Yong-Hyun Jeon, Jae-Eon Lee, Joon-Suk Park, Hoon Jang and Gabbine Wee
Curr. Issues Mol. Biol. 2024, 46(5), 3752-3762; https://doi.org/10.3390/cimb46050234 - 23 Apr 2024
Abstract
Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient
[...] Read more.
Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized–egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.
Full article
(This article belongs to the Topic Animal Models of Human Disease 2.0)
►▼
Show Figures
Figure 1
Open AccessArticle
Enhancing Yield and Improving Grain Quality in Japonica Rice: Targeted EHD1 Editing via CRISPR-Cas9 in Low-Latitude Adaptation
by
Jian Song, Liqun Tang, Honghuan Fan, Xiaozheng Xu, Xinlu Peng, Yongtao Cui and Jianjun Wang
Curr. Issues Mol. Biol. 2024, 46(4), 3741-3751; https://doi.org/10.3390/cimb46040233 - 22 Apr 2024
Abstract
The “Indica to Japonica” initiative in China focuses on adapting Japonica rice varieties from the northeast to the unique photoperiod and temperature conditions of lower latitudes. While breeders can select varieties for their adaptability, the sensitivity to light and temperature often
[...] Read more.
The “Indica to Japonica” initiative in China focuses on adapting Japonica rice varieties from the northeast to the unique photoperiod and temperature conditions of lower latitudes. While breeders can select varieties for their adaptability, the sensitivity to light and temperature often complicates and prolongs the process. Addressing the challenge of cultivating high-yield, superior-quality Japonica rice over expanded latitudinal ranges swiftly, in the face of these sensitivities, is critical. Our approach harnesses the CRISPR-Cas9 technology to edit the EHD1 gene in the premium northeastern Japonica cultivars Jiyuanxiang 1 and Yinongxiang 12, which are distinguished by their exceptional grain quality—increased head rice rates, gel consistency, and reduced chalkiness and amylose content. Field trials showed that these new ehd1 mutants not only surpass the wild types in yield when grown at low latitudes but also retain the desirable traits of their progenitors. Additionally, we found that disabling Ehd1 boosts the activity of Hd3a and RFT1, postponing flowering by approximately one month in the ehd1 mutants. This research presents a viable strategy for the accelerated breeding of elite northeastern Japonica rice by integrating genomic insights with gene-editing techniques suitable for low-latitude cultivation.
Full article
(This article belongs to the Special Issue Molecular Breeding and Genetics Research in Plants)
►▼
Show Figures
Figure 1
Open AccessArticle
Phospho-Chitooligosaccharides below 1 kDa Inhibit HIV-1 Entry In Vitro
by
Fatih Karadeniz and Se-Kwon Kim
Curr. Issues Mol. Biol. 2024, 46(4), 3729-3740; https://doi.org/10.3390/cimb46040232 - 22 Apr 2024
Abstract
Despite present antiviral agents that can effectively work against HIV-1 replication, side effects and drug resistance have pushed researchers toward novel approaches. In this context, there is a continued focus on discovering new and more effective antiviral compounds, particularly those that have a
[...] Read more.
Despite present antiviral agents that can effectively work against HIV-1 replication, side effects and drug resistance have pushed researchers toward novel approaches. In this context, there is a continued focus on discovering new and more effective antiviral compounds, particularly those that have a natural origin. Polysaccharides are known for their numerous bioactivities, including inhibiting HIV-1 infection and replication. In the present study, phosphorylated chitosan oligosaccharides (PCOSs) were evaluated for their anti-HIV-1 potential in vitro. Treatment with PCOSs effectively protected cells from HIV-1-induced lytic effects and suppressed the production of HIV-1 p24 protein. In addition, results show that PCOSs lost their protective effect upon post-infection treatment. According to the results of ELISA, PCOSs notably disrupted the binding of HIV-1 gp120 protein to T cell surface receptor CD4, which is required for HIV-1 entry. Overall, the results point out that PCOSs might prevent HIV-1 infection at the entry stage, possibly via blocking the viral entry through disruption of virus–cell fusion. Nevertheless, the current results only present the potential of PCOSs, and further studies to elucidate its action mechanism in detail are needed to employ phosphorylation of COSs as a method to develop novel antiviral agents.
Full article
(This article belongs to the Special Issue Drugs: Mechanisms of Action, Molecular Targets and Biological Activities, 2nd Edition)
►▼
Show Figures
Figure 1
Open AccessArticle
Analysis of microRNA Expression Profiles in Broiler Muscle Tissues by Feeding Different Levels of Guanidinoacetic Acid
by
Mengqian Liu, Mengyuan Li, Jinrui Ruan, Junjing Jia, Changrong Ge and Weina Cao
Curr. Issues Mol. Biol. 2024, 46(4), 3713-3728; https://doi.org/10.3390/cimb46040231 - 22 Apr 2024
Abstract
The aim of this study was to explore the molecular mechanisms through which different levels of GAA affect chicken muscle development by influencing miRNA expression, to lay a theoretical foundation for the identification of key functional small RNAs related to poultry muscle development,
[...] Read more.
The aim of this study was to explore the molecular mechanisms through which different levels of GAA affect chicken muscle development by influencing miRNA expression, to lay a theoretical foundation for the identification of key functional small RNAs related to poultry muscle development, and to provide new insights into the regulatory mechanisms of GAA on muscle development and meat quality in broilers. It provides a new theoretical basis for using GAA as a feed additive to improve feed performance. Small RNA sequencing technology was utilized to obtain the expression profiles of miRNA in the broiler pectoral muscle fed with different levels of GAA (0 g/kg, 1.2 g/kg and 3.6 g/kg). An analysis of differentially expressed miRNAs revealed 90 such miRNAs in the three combination comparisons, with gga-miR-130b-5p exhibiting significant differences across all three combinations. Furthermore, three of the differentially expressed miRNAs were performed by RT-qPCR verification, yielding results consistent with those obtained from small RNA sequencing. Target gene prediction, as well as the GO and KEGG enrichment analysis of differentially expressed miRNAs, indicated their involvement in muscle cell differentiation and other processes, particularly those associated with the MAPK signaling pathway. This study has, thus, provided valuable insights and resources for the further exploration of the miRNA molecular mechanism underlying the influence of guanidine acetic acid on broiler muscle development. Combined with previous studies and small RNA sequencing, adding 1.2 g/kg GAA to the diet can better promote the muscle development of broilers.
Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
►▼
Show Figures
Figure 1
Open AccessArticle
Effects of Lignin-Diverted Reductant with Polyphenol Oxidases on Cellulose Degradation by Wild and Mutant Types of Lytic Polysaccharide Monooxygenase
by
Kai Li, Yuan Wang, Xiao Guo and Bo Wang
Curr. Issues Mol. Biol. 2024, 46(4), 3694-3712; https://doi.org/10.3390/cimb46040230 - 21 Apr 2024
Abstract
Establishing a multi-enzyme synergistic lignocellulosic biodegradation system using lytic polysaccharide monooxygenase (LPMO) and polyphenol oxidases is vital for efficiently utilizing plant biomass waste, ultimately benefiting the carbon cycle and promoting environmental protection. Single-residue mutations of LPMO can improve the efficiency of lignocellulosic biomass
[...] Read more.
Establishing a multi-enzyme synergistic lignocellulosic biodegradation system using lytic polysaccharide monooxygenase (LPMO) and polyphenol oxidases is vital for efficiently utilizing plant biomass waste, ultimately benefiting the carbon cycle and promoting environmental protection. Single-residue mutations of LPMO can improve the efficiency of lignocellulosic biomass degradation. However, the activity of mutant-type LPMO in relation to lignin-diverted reducing agents has not been sufficiently explored. In this study, laccase and tyrosinase were initially investigated and their optimal conditions and impressive thermal stability were revealed, indicating their potential synergistic abilities with LPMO in lignocellulose biodegradation. When utilizing gallic acid as a reducing agent, the activities of LPMOs were increased by over 10%, which was particularly evident in mutant-type LPMOs after the addition of polyphenol oxidases. In particular, the combination of tyrosinase with either 4-hydroxy-3-methoxyphenylacetone or p-coumaric acid was shown to enhance the efficacy of LPMOs. Furthermore, the highest activity levels of wild-type LPMOs were observed with the addition of laccase and 3-methylcatechol. The similarities between wild and mutant LPMOs regarding their activities in lignin-diverted phenolic compounds and reducing agents are almost identical, suggesting that the single-residue mutation of LPMO does not have a detrimental effect on its performance. Above all, this study indicates that understanding the performance of both wild and mutant types of LPMOs in the presence of polyphenol oxidases and various reducing agents constitutes a key link in the industrialization of the multi-enzyme degradation of lignocellulose.
Full article
(This article belongs to the Section Molecular Plant Sciences)
►▼
Show Figures
Figure 1
Open AccessArticle
Signaling Transduction Pathways and G-Protein-Coupled Receptors in Different Stages of the Embryonic Diapause Termination Process in Artemia
by
Tong Hao, Zhentao Song, Mingzhi Zhang and Lingrui Zhang
Curr. Issues Mol. Biol. 2024, 46(4), 3676-3693; https://doi.org/10.3390/cimb46040229 - 20 Apr 2024
Abstract
Artemia is a widely distributed small aquatic crustacean, renowned for its ability to enter a state of embryonic diapause. The embryonic diapause termination (EDT) is closely linked to environmental cues, but the precise underlying mechanisms remain elusive. In this study, ATAC-seq and RNA-seq
[...] Read more.
Artemia is a widely distributed small aquatic crustacean, renowned for its ability to enter a state of embryonic diapause. The embryonic diapause termination (EDT) is closely linked to environmental cues, but the precise underlying mechanisms remain elusive. In this study, ATAC-seq and RNA-seq sequencing techniques were employed to explore the gene expression profiles in Artemia cysts 30 min after EDT. These profiles were compared with those during diapause and 5 h after EDT. The regulatory mechanisms governing the EDT process were analyzed through Gene Ontology (GO) enrichment analysis of differentially expressed genes. Furthermore, the active G-protein-coupled receptors (GPCRs) were identified through structural analysis. The results unveiled that the signaling transduction during EDT primarily hinges on GPCRs and the cell surface receptor signaling pathway, but distinct genes are involved across different stages. Hormone-mediated signaling pathways and the tachykinin receptor signaling pathway exhibited heightened activity in the ‘0–30 min’ group, whereas the Wnt signaling pathway manifested its function solely in the ‘30 min–5 h’ group. These results imply a complete divergence in the mechanisms of signal regulation during these two stages. Moreover, through structural analysis, five GPCRs operating at different stages of EDT were identified. These findings provide valuable insights into the signal regulation mechanisms governing Artemia diapause.
Full article
(This article belongs to the Special Issue Reproductive Biology and Germ Cell Development)
►▼
Show Figures
Figure 1
Open AccessReview
The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis
by
Kajetan Kiełbowski, Wiktoria Stańska, Estera Bakinowska, Marcin Rusiński and Andrzej Pawlik
Curr. Issues Mol. Biol. 2024, 46(4), 3640-3675; https://doi.org/10.3390/cimb46040228 - 19 Apr 2024
Abstract
Alarmins are immune-activating factors released after cellular injury or death. By secreting alarmins, cells can interact with immune cells and induce a variety of inflammatory responses. The broad family of alarmins involves several members, such as high-mobility group box 1, S100 proteins, interleukin-33,
[...] Read more.
Alarmins are immune-activating factors released after cellular injury or death. By secreting alarmins, cells can interact with immune cells and induce a variety of inflammatory responses. The broad family of alarmins involves several members, such as high-mobility group box 1, S100 proteins, interleukin-33, and heat shock proteins, among others. Studies have found that the concentrations and expression profiles of alarmins are altered in immune-mediated diseases. Furthermore, they are involved in the pathogenesis of inflammatory conditions. The aim of this narrative review is to present the current evidence on the role of alarmins in rheumatoid arthritis, osteoarthritis, and psoriasis. We discuss their potential involvement in mechanisms underlying the progression of these diseases and whether they could become therapeutic targets. Moreover, we summarize the impact of pharmacological agents used in the treatment of these diseases on the expression of alarmins.
Full article
(This article belongs to the Special Issue Molecular Research in Osteoarthritis and Osteoarticular Diseases)
►▼
Show Figures
Figure 1
Open AccessArticle
Phytocannabinoids CBD, CBG, and their Derivatives CBD-HQ and CBG-A Induced In Vitro Cytotoxicity in 2D and 3D Colon Cancer Cell Models
by
Dorota Bęben, Oliwia Siwiela, Anna Szyjka, Michał Graczyk, Daniel Rzepka, Ewa Barg and Helena Moreira
Curr. Issues Mol. Biol. 2024, 46(4), 3626-3639; https://doi.org/10.3390/cimb46040227 - 19 Apr 2024
Abstract
Phytocannabinoids, compounds found in Cannabis sativa L., are used in oncology and palliative care to reduce the adverse reactions of standard therapies. Cancer patients use formulations of Cannabis sativa L. to manage the anxiety, pain, and nausea associated with cancer treatment, and there
[...] Read more.
Phytocannabinoids, compounds found in Cannabis sativa L., are used in oncology and palliative care to reduce the adverse reactions of standard therapies. Cancer patients use formulations of Cannabis sativa L. to manage the anxiety, pain, and nausea associated with cancer treatment, and there is growing evidence that some of them may exhibit anticancer properties. In this study, we tested the anticancer potential of selected cannabinoids CBD (cannabidiol) and its quinone derivative CBD-HQ (cannabidiol hydroquinone), CBG (cannabigerol) and its acid derivative CBG-A (cannabigerolic acid), as well as a combination of CBD+CBG on the colon cancer cell line SW-620. The MTT assay was used to determine the cannabinoids’ ability to induce colon cancer cell death. All cannabinoids were cytotoxic at the lowest concentration (3 μg/mL). The half maximal inhibitory concentration (IC50) ranged from 3.90 to 8.24 μg/mL, depending on the substance. Cytotoxicity was confirmed in a 3D spheroidal cell culture with calcein and propidium iodide staining. The amount of intracellular reactive oxygen species (ROS) was examined using a DCF-DA assay. CBG showed the lowest antioxidant activity of all the cannabinoids tested. The level of intracellular ROS decreased only by 0.7–18%. However, CBG-A induced the strongest reduction in ROS level by 31–39%. Our results suggest that cannabinoids represent an interesting research direction with great implementation potential. These preliminary results represent the beginning of research into the potential of these substances for anticancer treatment and underscore the potential for further research.
Full article
(This article belongs to the Special Issue Phytochemicals and Cancer, 2nd Edition)
►▼
Show Figures
Figure 1
Open AccessArticle
Correlation between the RNA Expression and the DNA Methylation of Estrogen Receptor Genes in Normal and Malignant Human Tissues
by
Ju Rong, Xiaojun Xie, Yongdong Niu and Zhongjing Su
Curr. Issues Mol. Biol. 2024, 46(4), 3610-3625; https://doi.org/10.3390/cimb46040226 - 19 Apr 2024
Abstract
Estrogen plays a multifaceted function in humans via interacting with the estrogen receptors ERα, ERβ, and G protein-coupled estrogen receptor 1 (GPER1). Previous research has predominantly concentrated on elucidating the signaling route of estrogen. However, the comprehensive understanding of the expression profile and
[...] Read more.
Estrogen plays a multifaceted function in humans via interacting with the estrogen receptors ERα, ERβ, and G protein-coupled estrogen receptor 1 (GPER1). Previous research has predominantly concentrated on elucidating the signaling route of estrogen. However, the comprehensive understanding of the expression profile and control of these estrogen receptors in various human tissues is not well known. In the present study, the RNA levels of estrogen receptors in various normal and malignant human tissues were retrieved from the human protein atlas, the cancer genome atlas (TCGA), and the genotype-tissue expression (GTEx) databases for analyzing the expression profile of estrogen receptors through gene expression profiling interactive analysis (GEPIA). The status of DNA methylation of estrogen receptor genes from TCGA were analyzed through the software Wanderer and cBioPortal. The MethSurv tool was utilized to estimate the relevance between specific cytosine–guanine (CG) methylation and tumor survival. The expression profile analysis revealed that ERα, ERβ, and GPER1 have unique expression patterns in diverse tissues and malignancies. The interesting results were the higher expression of ERβ RNA in the male testis than in females and the positive association between the RNA level of ERα and the androgen receptor in different human normal tissues. Especially, the significant changes in GPER1 expression in multiple malignancies showed a consistent decrease with no exception, which indicates the role of GPER1 in common tumor inhibition. The finding on the expression profile provides clues for exploring novel potential physiological and pathophysiological functions of estrogen. The DNA methylation analysis manifested that the expression of GPER1 and ERα showed a substantial correlation with the methylation of specific CG sites in the cis-regulating region of the gene. However, no such association was observed for ERβ. When comparing tumor tissues to normal tissues, the DNA methylation of certain CG sites of estrogen receptors showed a correlation with tumor survival but did not always correlate with the expression of that gene or with the expression of DNA methyltransferases. We proposed that the variation in DNA methylation at different CG sites in estrogen receptor genes had other functions beyond its regulatory role in its gene expression, and this might be associated with the progression and therapy efficiency of the tumor based on the modulation of the chromatin configuration.
Full article
(This article belongs to the Special Issue New Advances in Non-coding RNAs)
►▼
Show Figures
Figure 1
Open AccessArticle
Microbiome Sex-Related Diversity in Non-Muscle-Invasive Urothelial Bladder Cancer
by
Konrad Bilski, Natalia Żeber-Lubecka, Maria Kulecka, Michalina Dąbrowska, Aneta Bałabas, Jerzy Ostrowski, Aleksandra Dobruch and Jakub Dobruch
Curr. Issues Mol. Biol. 2024, 46(4), 3595-3609; https://doi.org/10.3390/cimb46040225 - 19 Apr 2024
Abstract
Sex-specific discrepancies in bladder cancer (BCa) are reported, and new studies imply that microbiome may partially explain the diversity. We aim to provide characterization of the bladder microbiome in both sexes diagnosed with non-muscle-invasive BCa with specific insight into cancer grade. In our
[...] Read more.
Sex-specific discrepancies in bladder cancer (BCa) are reported, and new studies imply that microbiome may partially explain the diversity. We aim to provide characterization of the bladder microbiome in both sexes diagnosed with non-muscle-invasive BCa with specific insight into cancer grade. In our study, 16S rRNA next-generation sequencing was performed on midstream urine, bladder tumor sample, and healthy-appearing bladder mucosa. Bacterial DNA was isolated using QIAamp Viral RNA Mini Kit. Metagenomic analysis was performed using hypervariable fragments of the 16S rRNA gene on Ion Torrent Personal Genome Machine platform. Of 41 sample triplets, 2153 taxa were discovered: 1739 in tumor samples, 1801 in healthy-appearing bladder mucosa and 1370 in midstream urine. Women were found to have smaller taxa richness in Chao1 index than men (p = 0.03). In comparison to low-grade tumors, patients with high-grade lesions had lower bacterial diversity and richness in urine. Significant differences between sexes in relative abundance of communities at family level were only observed in high-grade tumors.
Full article
(This article belongs to the Section Molecular Microbiology)
►▼
Show Figures
Figure 1
Open AccessArticle
Association between KRAS and PIK3CA Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line
by
Kosuke Kanno, Kentaro Nakayama, Sultana Razia, Sohel Hasibul Islam, Zahan Umme Farzana, Shahataj Begum Sonia, Hitomi Yamashita, Masako Ishikawa, Tomoka Ishibashi, Kayo Imamura, Tohru Kiyono and Satoru Kyo
Curr. Issues Mol. Biol. 2024, 46(4), 3579-3594; https://doi.org/10.3390/cimb46040224 - 19 Apr 2024
Abstract
Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations
[...] Read more.
Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.
Full article
(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)
►▼
Show Figures
Figure 1
Open AccessArticle
Alginate Improves the Chondrogenic Capacity of 3D PCL Scaffolds In Vitro: A Histological Approach
by
Lara Milián, María Oliver-Ferrándiz, Ignacio Peregrín, María Sancho-Tello, José Javier Martín-de-Llano, Cristina Martínez-Ramos, Carmen Carda and Manuel Mata
Curr. Issues Mol. Biol. 2024, 46(4), 3563-3578; https://doi.org/10.3390/cimb46040223 - 19 Apr 2024
Abstract
Polycaprolactone (PCL) scaffolds have demonstrated an effectiveness in articular cartilage regeneration due to their biomechanical properties. On the other hand, alginate hydrogels generate a 3D environment with great chondrogenic potential. Our aim is to generate a mixed PCL/alginate scaffold that combines the chondrogenic
[...] Read more.
Polycaprolactone (PCL) scaffolds have demonstrated an effectiveness in articular cartilage regeneration due to their biomechanical properties. On the other hand, alginate hydrogels generate a 3D environment with great chondrogenic potential. Our aim is to generate a mixed PCL/alginate scaffold that combines the chondrogenic properties of the two biomaterials. Porous PCL scaffolds were manufactured using a modified salt-leaching method and embedded in a culture medium or alginate in the presence or absence of chondrocytes. The chondrogenic capacity was studied in vitro. Type II collagen and aggrecan were measured by immunofluorescence, cell morphology by F-actin fluorescence staining and gene expression of COL1A1, COL2A1, ACAN, COL10A1, VEGF, RUNX1 and SOX6 by reverse transcription polymerase chain reaction (RT-PCR). The biocompatibility of the scaffolds was determined in vivo using athymic nude mice and assessed by histopathological and morphometric analysis. Alginate improved the chondrogenic potential of PCL in vitro by increasing the expression of type II collagen and aggrecan, as well as other markers related to chondrogenesis. All scaffolds showed good biocompatibility in the in vivo model. The presence of cells in the scaffolds induced an increase in vascularization of the PCL/alginate scaffolds. The results presented here reinforce the benefits of the combined use of PCL and alginate for the regeneration of articular cartilage.
Full article
(This article belongs to the Section Molecular Medicine)
►▼
Show Figures
Graphical abstract
Journal Menu
► ▼ Journal MenuJournal Browser
► ▼ Journal Browser-
arrow_forward_ios
Forthcoming issue
arrow_forward_ios Current issue - Volumes not published by MDPI
- Vol. 42 (2021)
- Vol. 41 (2021)
- Vol. 40 (2021)
- Vol. 39 (2020)
- Vol. 38 (2020)
- Vol. 37 (2020)
- Vol. 36 (2020)
- Vol. 35 (2020)
- Vol. 34 (2019)
- Vol. 33 (2019)
- Vol. 32 (2019)
- Vol. 31 (2019)
- Vol. 30 (2019)
- Vol. 29 (2018)
- Vol. 28 (2018)
- Vol. 27 (2018)
- Vol. 26 (2018)
- Vol. 25 (2018)
- Vol. 24 (2017)
- Vol. 23 (2017)
- Vol. 22 (2017)
- Vol. 21 (2017)
- Vol. 20 (2016)
- Vol. 19 (2016)
- Vol. 18 (2016)
- Vol. 17 (2015)
- Vol. 16 (2014)
- Vol. 15 (2013)
- Vol. 14 (2012)
- Vol. 13 (2011)
- Vol. 12 (2010)
- Vol. 11 (2009)
- Vol. 10 (2008)
- Vol. 9 (2007)
- Vol. 8 (2006)
- Vol. 7 (2005)
- Vol. 6 (2004)
- Vol. 5 (2003)
- Vol. 4 (2002)
- Vol. 3 (2001)
- Vol. 2 (2000)
- Vol. 1 (1999)
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biomedicines, CIMB, Endocrines, IJMS, JMP, Life, Reprod. Med.
Pathogenesis of Pregnancy-Related Complications 2.0
Topic Editors: Ilona Hromadnikova, Katerina KotlabovaDeadline: 31 August 2024
Topic in
BioMed, Biomedicines, CIMB, Foods, Nutrients
Novel Therapeutic Nutrient Molecules, 2nd Volume
Topic Editors: Sathish Kumar Natarajan, Jiujiu Yu, Corrine K Hanson, Melissa ThoeneDeadline: 31 December 2024
Topic in
BioChem, Biomolecules, CIMB, Molecules, Pharmaceutics, Sci. Pharm.
Design, Synthesis and Biological Evaluation of Novel Small Molecules as Multi-target Enzyme Inhibitors
Topic Editors: Davide Moi, Daniele Passarella, Andrea CitarellaDeadline: 31 January 2025
Topic in
CIMB, Molecules, Pharmaceuticals, Pharmaceutics, Sci. Pharm.
Challenges and Opportunities in Drug Delivery Research
Topic Editors: Lenuta Profire, Ioana Mirela VasincuDeadline: 31 March 2025
Conferences
Special Issues
Special Issue in
CIMB
Molecular Research in Food Science
Guest Editors: Chih-Cheng Lin, Jia-Feng ChangDeadline: 30 April 2024
Special Issue in
CIMB
Advanced Research of Ionizing Radiation in Cancers
Guest Editors: Carlo Aprile, Lorenzo Lodola, Onelio GeattiDeadline: 31 May 2024
Special Issue in
CIMB
Molecular Research on Female Reproductive Diseases
Guest Editor: Hsien-Ming WuDeadline: 30 June 2024
Special Issue in
CIMB
Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies
Guest Editors: Kinga Lis, Natalia Ukleja-SokołowskaDeadline: 31 July 2024
Topical Collections
Topical Collection in
CIMB
Feature Papers Collection in Molecular Microbiology
Collection Editor: Bruce Seal
Topical Collection in
CIMB
Application of Natural and Pseudo Natural Products in Drug Discovery and Development
Collection Editor: Hidayat Hussain
Topical Collection in
CIMB
Feature Papers in Current Issues in Molecular BiologyCollection Editor: Madhav Bhatia