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
Topical Clonidine Accelerates Cutaneous Wound Healing in Diabetic Rats by Regulating the Expression of Related Cytokine Signaling
Curr. Issues Mol. Biol. 2024, 46(6), 5668-5681; https://doi.org/10.3390/cimb46060339 (registering DOI) - 6 Jun 2024
Abstract
Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision
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Based on the analgesic and anti-inflammatory effects of clonidine in previous studies, we hypothesized that clonidine could accelerate wound healing in rats by regulating the expression of related cytokines. In this study, the wound healing effect of clonidine was evaluated using an excision wound model in diabetic rats and a HaCaT cell model. The wounds were treated daily with topical clonidine. The results analyzed by ImageJ2 software show that the wounds of the rats that were treated with 15 ng/mL clonidine recovered faster, and the wound size was also significantly reduced compared to the control group. Western blot assays determined that clonidine induced an increase in the expression of vascular growth factors, namely, Ang-1, Ang-2, and VEGF. Moreover, clonidine demonstrated a rescuing effect on JAK2 within the JAK/STAT pathway by inhibiting SOCS3 expression, leading to decreased SOCS3 levels and increased expression of JAK2 and phospho-STAT3. Histopathological analysis revealed that clonidine promoted complete epithelial repair and minimized inflammation in skin tissue. Additionally, clonidine stimulated HaCaT cell proliferation in vitro and enhanced cellular energy levels in the presence of AGEs. In conclusion, clonidine promoted vascular growth and wound healing by stimulating the expression of cytokines that are beneficial for wound healing.
Full article
(This article belongs to the Section Molecular Pharmacology)
Open AccessCommunication
Protective Effect of Red Light-Emitting Diode against UV-B Radiation-Induced Skin Damage in SKH:HR-2 Hairless Mice
by
Eun-Chae Cho, Surin Ahn, Kyung-Ok Shin, Joon Byeong Lee, Hyo-Jeong Hwang and Yean-Jung Choi
Curr. Issues Mol. Biol. 2024, 46(6), 5655-5667; https://doi.org/10.3390/cimb46060338 - 6 Jun 2024
Abstract
In this in vivo study on hairless mice, we examined the effects of light-emitting diode (LED) treatment applied prior to ultraviolet B (UVB) irradiation. We found that pre-treating with LED improved skin morphological and histopathological conditions compared to those only exposed to UVB
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In this in vivo study on hairless mice, we examined the effects of light-emitting diode (LED) treatment applied prior to ultraviolet B (UVB) irradiation. We found that pre-treating with LED improved skin morphological and histopathological conditions compared to those only exposed to UVB irradiation. In our study, histological evaluation of collagen and elastic fibers after LED treatment prior to UVB irradiation showed that this pretreatment significantly enhanced the quality of fibers, which were otherwise poor in density and irregularly arranged due to UV exposure alone. This suggests that LED treatment promotes collagen and elastin production, leading to improved skin properties. Additionally, we observed an increase in Claudin-1 expression and a reduction in nuclear factor-erythroid 2-related factor 2 (Nrf-2) and heme-oxygenase 1 (HO-1) expression within the LED-treated skin tissues, suggesting that LED therapy may modulate key skin barrier proteins and oxidative stress markers. These results demonstrate that pretreatment with LED light can enhance the skin’s resistance to UVB-induced damage by modulating gene regulation associated with skin protection. Further investigations are needed to explore the broader biological effects of LED therapy on other tissues such as blood vessels. This study underscores the potential of LED therapy as a non-invasive approach to enhance skin repair and counteract the effects of photoaging caused by UV exposure.
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(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessReview
Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment
by
Giulia Spoto, Graziana Ceraolo, Ambra Butera, Gabriella Di Rosa and Antonio Gennaro Nicotera
Curr. Issues Mol. Biol. 2024, 46(6), 5632-5654; https://doi.org/10.3390/cimb46060337 - 6 Jun 2024
Abstract
Chorea is a hyperkinetic movement disorder frequently observed in the pediatric population, and, due to advancements in genetic techniques, an increasing number of genes have been associated with this disorder. In genetic conditions, chorea may be the primary feature of the disorder, or
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Chorea is a hyperkinetic movement disorder frequently observed in the pediatric population, and, due to advancements in genetic techniques, an increasing number of genes have been associated with this disorder. In genetic conditions, chorea may be the primary feature of the disorder, or be part of a more complex phenotype characterized by epileptic encephalopathy or a multisystemic syndrome. Moreover, it can appear as a persistent disorder (chronic chorea) or have an episodic course (paroxysmal chorea). Managing chorea in childhood presents challenges due to its varied clinical presentation, often involving a spectrum of hyperkinetic movement disorders alongside neuropsychiatric and multisystemic manifestations. Furthermore, during infancy and early childhood, transient motor phenomena resembling chorea occurring due to the rapid nervous system development during this period can complicate the diagnosis. This review aims to provide an overview of the main genetic causes of pediatric chorea that may manifest during infancy and early childhood, focusing on peculiarities that can aid in differential diagnosis among different phenotypes and discussing possible treatment options.
Full article
(This article belongs to the Special Issue Complex Molecular Mechanism of Monogenic Diseases 2.0)
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Open AccessArticle
Free Salivary Amino Acid Profile in Breast Cancer: Clinicopathological and Molecular Biological Features
by
Lyudmila V. Bel’skaya, Elena A. Sarf and Denis V. Solomatin
Curr. Issues Mol. Biol. 2024, 46(6), 5614-5631; https://doi.org/10.3390/cimb46060336 - 5 Jun 2024
Abstract
The study of salivary amino acid profiles has attracted the attention of researchers, since amino acids are actively involved in most metabolic processes, including breast cancer. In this study, we analyzed the amino acid profile of saliva in a sample including all molecular
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The study of salivary amino acid profiles has attracted the attention of researchers, since amino acids are actively involved in most metabolic processes, including breast cancer. In this study, we analyzed the amino acid profile of saliva in a sample including all molecular biological subtypes of breast cancer to obtain a more complete picture and evaluate the potential utility of individual amino acids or their combinations for diagnostic purposes. This study included 116 patients with breast cancer, 24 patients with benign breast disease, and 25 healthy controls. From all patients, strictly before the start of treatment, saliva samples were collected, and the quantitative content of 26 amino acids was determined. Statistically significant differences between the three groups are shown in the content of Asp, Gly, Leu + Ile, Orn, Phe, Pro, Thr, and Tyr. To differentiate the three groups from each other, a decision tree was built. To construct it, we selected those amino acids for which the change in concentrations in the subgroups was multidirectional (GABA, Hyl, Arg, His, Pro, and Car). For the first time, it is shown that the amino acid profile of saliva depends on the molecular biological subtype of breast cancer. The most significant differences are shown for the luminal B HER2-positive and TNBC subgroups. In our opinion, it is critically important to consider the molecular biological subtype of breast cancer when searching for potential diagnostic markers.
Full article
(This article belongs to the Collection Molecular Mechanisms in Human Diseases)
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Open AccessReview
Exploring the Therapeutic Potential: Bioactive Molecules and Dietary Interventions in Multiple Sclerosis Management
by
Gabriele Tancreda, Silvia Ravera and Isabella Panfoli
Curr. Issues Mol. Biol. 2024, 46(6), 5595-5613; https://doi.org/10.3390/cimb46060335 - 3 Jun 2024
Abstract
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It
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Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system, the etiology of which is still unclear. Its hallmarks are inflammation and axonal damage. As a disease primarily impacting younger individuals, the social cost of MS is high. It has been proposed that environmental factors, smoking, and dietary habits acting on a genetic susceptibility play a role in MS. Recent studies indicate that diet can significantly influence the onset and progression of MS. This review delves into the impact of natural bioactive molecules on MS development and explores the dietary interventions that hold promise in managing the disease. Dietary patterns, including ketogenic and Mediterranean diets, are discussed. Theories about the potential mechanistic associations beneath the noted effects are also proposed. Several dietary components and patterns demonstrated the potential for a significant impact on MS. However, extensive prospective clinical trials are necessary to fully understand the role of natural bioactive molecules as disease modifiers in MS.
Full article
(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders and Remyelination Strategies of the CNS)
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Open AccessReview
Targeting Cancers with oHSV-Based Oncolytic Viral Immunotherapy
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Rakin Tammam Nasar, Ifeanyi Kingsley Uche and Konstantin G. Kousoulas
Curr. Issues Mol. Biol. 2024, 46(6), 5582-5594; https://doi.org/10.3390/cimb46060334 - 3 Jun 2024
Abstract
The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies (ACTs), has revolutionized traditional cancer treatment. However, these immunotherapeutic modalities have variable efficacies, and many of them exhibit adverse effects. Oncolytic viral
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The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies (ACTs), has revolutionized traditional cancer treatment. However, these immunotherapeutic modalities have variable efficacies, and many of them exhibit adverse effects. Oncolytic viral Immunotherapy (OViT), whereby viruses are used to directly or indirectly induce anti-cancer immune responses, is emerging as a novel immunotherapy for treating patients with different types of cancer. The herpes simplex virus type-1 (HSV-1) possesses many characteristics that inform its use as an effective OViT agents and remains a leading candidate. Its recent clinical success resulted in the Food and Drug Administration (FDA) approval of Talimogene laherparevec (T-VEC or Imlygic) in 2015 for the treatment of advanced melanoma. In this review, we discuss recent advances in the development of oncolytic HSV-1-based OViTs, their anti-tumor mechanism of action, and efficacy data from recent clinical trials. We envision this knowledge may be used to inform the rational design and application of future oHSV in cancer treatment.
Full article
(This article belongs to the Special Issue Research on Virus-Induced Cellular and Molecular Responses)
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Open AccessArticle
Network Pharmacology Analysis, Molecular Docking Integrated Experimental Verification Reveal the Mechanism of Gynostemma pentaphyllum in the Treatment of Type II Diabetes by Regulating the IRS1/PI3K/Akt Signaling Pathway
by
Songqin Yang, Mao Zhao, Mingxing Lu, Yuhan Feng, Xia Zhang, Daoping Wang and Wenwen Jiang
Curr. Issues Mol. Biol. 2024, 46(6), 5561-5581; https://doi.org/10.3390/cimb46060333 - 1 Jun 2024
Abstract
Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of
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Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3β and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.
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(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)
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Open AccessBrief Report
Construction of a Synergy Combination Model for Turmeric (Curcuma longa L.) and Black Pepper (Piper nigrum L.) Extracts: Enhanced Anticancer Activity against A549 and NCI-H292 Human Lung Cancer Cells
by
Hyun-Ki Cho, Chang-Gyun Park and Heung-Bin Lim
Curr. Issues Mol. Biol. 2024, 46(6), 5551-5560; https://doi.org/10.3390/cimb46060332 - 1 Jun 2024
Abstract
Extensive research on medicinal herbs for bioactive compounds proposes that they could replace synthetic drugs, reducing side effects and economic burdens. Especially, interest in the synergistic benefits of natural products is increasing, implying that their combined use may enhance therapeutic effectiveness. This study
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Extensive research on medicinal herbs for bioactive compounds proposes that they could replace synthetic drugs, reducing side effects and economic burdens. Especially, interest in the synergistic benefits of natural products is increasing, implying that their combined use may enhance therapeutic effectiveness. This study aimed to explore the synergetic effects of turmeric (Curcuma longa L.) and black pepper (Piper nigrum L.) extract on lung normal (MRC-5) and cancer (A549 and NCI-H292) cell lines. The turmeric extract (TM) only affected the lung cancer cell lines, but it had no impact on the MRC-5 cell line. On the other hand, the black pepper extract (BP) did not cause any damage to either the lung normal or cancer cell lines, even at concentrations of up to 400 µg/mL. Response surface methodology was used to predict the ideal synergistic concentrations (EC50) of TM and BP, which were found to be 48.5 and 241.7 µg/mL, respectively. Notably, the selected condition resulted in higher cytotoxicity compared to the exposure to TM alone, indicating a potent synergetic effect. The rate of curcumin degradation under this combined treatment was significantly decreased to 49.72 ± 5.00 nmol/h/µg for A549 cells and 47.53 ± 4.78 nmol/h/µg for NCI-H292 cells, respectively, as compared to curcumin alone. Taken together, this study confirmed the potent synergistic effect of TM and BP on lung cancer cell lines. Further research is required to identify their specific synergetic mechanisms. Our findings provide crucial foundational data on the synergistic effects of TM and BP.
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(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)
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Open AccessRetraction
RETRACTED: Al-Salmi, F.A.; Hamza, R.Z. Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats. Curr. Issues Mol. Biol. 2022, 44, 94–104
by
Fawziah A. Al-Salmi and Reham Z. Hamza
Curr. Issues Mol. Biol. 2024, 46(6), 5550; https://doi.org/10.3390/cimb46060331 - 31 May 2024
Abstract
Current Issues in Molecular Biology Editorial Office retracts the article titled “Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats” [...]
Full article
(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)
Open AccessReview
Glutathione in HIV-Associated Neurocognitive Disorders
by
Thomas Erdos, Mika Masuda and Vishwanath Venketaraman
Curr. Issues Mol. Biol. 2024, 46(6), 5530-5549; https://doi.org/10.3390/cimb46060330 - 31 May 2024
Abstract
A large portion of patients with Human Immunodeficiency Virus (HIV) have neurologic sequelae. Those with better-controlled HIV via antiretroviral therapies generally have less severe neurologic symptoms. However, for many patients, antiretrovirals do not adequately resolve symptoms. Since much of the pathogenesis of HIV/AIDS
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A large portion of patients with Human Immunodeficiency Virus (HIV) have neurologic sequelae. Those with better-controlled HIV via antiretroviral therapies generally have less severe neurologic symptoms. However, for many patients, antiretrovirals do not adequately resolve symptoms. Since much of the pathogenesis of HIV/AIDS (Autoimmune Deficiency Syndrome) involves oxidative stress either directly, through viral interaction, or indirectly, through inflammatory mechanisms, we have reviewed relevant trials of glutathione supplementation in each of the HIV-associated neurocognitive diseases and have found disease-specific results. For diseases for which trials have not been completed, predicted responses to glutathione supplementation are made based on relevant mechanisms seen in the literature. It is not sufficient to conclude that all HIV-associated neurocognitive disorders (HAND) will benefit from the antioxidant effects of glutathione supplementation. The potential effects of glutathione supplementation in patients with HAND are likely to differ based on the specific HIV-associated neurocognitive disease.
Full article
(This article belongs to the Special Issue Infectious Diseases and Molecular Epidemiology: Focus on Pathogenic Microorganisms)
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Open AccessArticle
Diversity of Expression Patterns of Lr34, Lr67, and Candidate Genes towards Lr46 with Analysis of Associated miRNAs in Common Wheat Hybrids in Response to Puccinia triticina Fungus
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Julia Spychała, Agnieszka Tomkowiak, Aleksandra Noweiska, Roksana Bobrowska, Jan Bocianowski, Aleksandra Sobiech and Michał Tomasz Kwiatek
Curr. Issues Mol. Biol. 2024, 46(6), 5511-5529; https://doi.org/10.3390/cimb46060329 - 31 May 2024
Abstract
Leaf rust caused by Puccinia triticina (Pt) is one of the most dangerous diseases causing significant losses in common wheat crops. In adult plants resistant to rust, a horizontal adult plant resistance (APR) type is observed, which protects the plant against multiple pathogen
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Leaf rust caused by Puccinia triticina (Pt) is one of the most dangerous diseases causing significant losses in common wheat crops. In adult plants resistant to rust, a horizontal adult plant resistance (APR) type is observed, which protects the plant against multiple pathogen races and is distinguished by greater persistence under production conditions. Crucial pleiotropic slow-rust genes such as Lr34, Lr46, Lr67, and Lr68, in combination with other genes of lesser influence, continue to increase durable resistance to rust diseases. Based on our previous results, we selected four candidate genes for Lr46 out of ten candidates and analysed them for expression before and after inoculation by P. triticina. As part of our study, we also investigated the expression patterns of miRNA molecules complementary to Lr34 and the candidate genes. The aim of the study was to analyse the expression profiles of candidate genes for the Lr46 gene and the Lr34 and Lr67 genes responsible for the differential leaf-rust resistance of hybrid forms of the F1 generation resulting from crosses between the Glenlea cultivar and cultivars from Polish breeding companies. In addition, the expression of five miRNAs (tae-miR9653b, tae-miR5384-3p, tae-miR9780, tae-miR9775 and tae-miR164), complementary to Lr34, and selected candidate genes were analysed using stem-loop RT-PCR and ddPCR. Biotic stress was induced in adult plants by inoculation with Pt fungal spores, under controlled conditions. Plant material was collected before and 6, 12, 24, and 48 h after inoculation (hpi). Differences in expression patterns of Lr34, Lr67, and candidate genes (for Lr46) were analysed by qRT-PCR and showed that gene expression changed at the analysed time points. Identification of molecular markers coupled to the Lr genes studied was also carried out to confirm the presence of these genes in wheat hybrids. qRT-PCR was used to examine the expression levels of the resistance genes. The highest expression of Lr46/Yr29 genes (Lr46-Glu2, Lr46-RLK1, Lr46-RLK2, and Lr46-RLK3) occurred at 12 and 24 hpi, and such expression profiles were obtained for only one candidate gene among the four genes analysed (Lr46-Glu2), indicating that it may be involved in resistance mechanisms of response to Pt infection.
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(This article belongs to the Special Issue Advanced Research in Wheat Genome and Breeding)
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Open AccessArticle
Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value
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Safia Iqbal, Md. Rezaul Karim, Shahnawaz Mohammad, Ramya Mathiyalagan, Md. Niaj Morshed, Deok-Chun Yang, Hyocheol Bae, Esrat Jahan Rupa and Dong Uk Yang
Curr. Issues Mol. Biol. 2024, 46(6), 5488-5510; https://doi.org/10.3390/cimb46060328 - 30 May 2024
Abstract
The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3.
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The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein–protein interactions, we also chose a collection of well-known functional protein partners for pleckstrin. Investigations were also carried out on the relationship between pleckstrins and other cancers regarding mutations and copy number alterations. The cumulative impact of pleckstrin and their associated genes on various cancers, Gene Ontology (GO), and pathway analyses were used for their evaluation. Thus, the expression profiles of PHLDA family members and their prognosis in various cancers may be revealed by this study. During this multiomics analysis, we found that among the PHLDA family, PHLDA1 may be a therapeutic target for several cancers, including kidney, colon, and brain cancer, while PHLDA2 can be a therapeutic target for cancers of the colon, esophagus, and pancreas. Additionally, PHLDA3 may be a useful therapeutic target for ovarian, renal, and gastric cancer.
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(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)
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Open AccessReview
Positive Effects of Physical Activity on Insulin Signaling
by
Paulina Małkowska
Curr. Issues Mol. Biol. 2024, 46(6), 5467-5487; https://doi.org/10.3390/cimb46060327 - 30 May 2024
Abstract
Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies consistently demonstrate a strong association between physical activity levels and insulin sensitivity. Regular exercise interventions were shown to significantly improve
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Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies consistently demonstrate a strong association between physical activity levels and insulin sensitivity. Regular exercise interventions were shown to significantly improve glycemic control, highlighting exercise as a recommended therapeutic strategy for reducing insulin resistance. Physical inactivity is closely linked to islet cell insufficiency, exacerbating insulin resistance through various pathways including ER stress, mitochondrial dysfunction, oxidative stress, and inflammation. Conversely, physical training and exercise preserve and restore islet function, enhancing peripheral insulin sensitivity. Exercise interventions stimulate β-cell proliferation through increased circulating levels of growth factors, further emphasizing its role in maintaining pancreatic health and glucose metabolism. Furthermore, sedentary lifestyles contribute to elevated oxidative stress levels and ceramide production, impairing insulin signaling and glucose metabolism. Regular exercise induces anti-inflammatory responses, enhances antioxidant defenses, and promotes mitochondrial function, thereby improving insulin sensitivity and metabolic efficiency. Encouraging individuals to adopt active lifestyles and engage in regular exercise is crucial for preventing and managing insulin resistance and related metabolic disorders, ultimately promoting overall health and well-being.
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(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)
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Open AccessArticle
Application of the TaqMan ARMS-PCR Approach for Genotyping Drug-Induced Hearing Loss Using Dried Blood Samples
by
Jiefeng Tan, Xiaoqing Zhang, Xue Wei and Min Ding
Curr. Issues Mol. Biol. 2024, 46(6), 5454-5466; https://doi.org/10.3390/cimb46060326 - 29 May 2024
Abstract
A single nucleotide variant in mitochondrial DNA (mtDNA) 1555A>G is associated with drug-induced hearing loss. For the 1555A>G mutation site, 1555A wild-type and 1555G mutant-type plasmids were constructed, respectively. In this study, a PCR method based on the TaqMan amplification refractory mutation system
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A single nucleotide variant in mitochondrial DNA (mtDNA) 1555A>G is associated with drug-induced hearing loss. For the 1555A>G mutation site, 1555A wild-type and 1555G mutant-type plasmids were constructed, respectively. In this study, a PCR method based on the TaqMan amplification refractory mutation system was proposed to detect mtDNA 1555A>G. A common upstream primer, a common TaqMan probe, and two downstream allele-specific primers with mismatched bases were designed. One-step amplification and detection of the wild-type and mutant type at the 1555 site were realized for the deafness-related gene through two reactions. Based on this detection method, the minimum detection limit of the wild-type and mutant type detection systems for plasmids was 50 copies/μL. The minimum sensitivity for the detection of nucleic acids in real dried blood spot (DBS) samples was 0.1 ng/μL. In the normal DBS DNA sample, the detection limit of the mutation abundance reached 0.78%. The specificity of the detection method was 100%, and the coefficient of variation was less than 3.36%. This approach was validated using clinical DNA extracted from 113 DBS samples of newborns. Additionally, it showed 100% agreement with bi-directional Sanger sequencing. It can be used as an optional method for the clinical detection of deafness-related genes.
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(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessReview
Molecular Mechanisms in the Design of Novel Targeted Therapies for Neurodegenerative Diseases
by
Ilona Nowak, Marlena Paździor, Robert Sarna and Marcel Madej
Curr. Issues Mol. Biol. 2024, 46(6), 5436-5453; https://doi.org/10.3390/cimb46060325 - 29 May 2024
Abstract
Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human
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Neurodegenerative diseases are a diverse group of diseases characterized by a progressive loss of neurological function due to damage to nerve cells in the central nervous system. In recent years, there has been a worldwide increase in the expanding associated with increasing human life expectancy. Molecular mechanisms control many of the essential life processes of cells, such as replication, transcription, translation, protein synthesis and gene regulation. These are complex interactions that form the basis for understanding numerous processes in the organism and developing new diagnostic and therapeutic approaches. In the context of neurodegenerative diseases, molecular basis refers to changes at the molecular level that cause damage to or degeneration of nerve cells. These may include protein aggregates leading to pathological structures in brain cells, impaired protein transport in nerve cells, mitochondrial dysfunction, inflammatory processes or genetic mutations that impair nerve cell function. New medical therapies are based on these mechanisms and include gene therapies, reduction in inflammation and oxidative stress, and the use of miRNAs and regenerative medicine. The aim of this study was to bring together the current state of knowledge regarding selected neurodegenerative diseases, presenting the underlying molecular mechanisms involved, which could be potential targets for new forms of treatment.
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(This article belongs to the Special Issue Molecular Genetics and Genomics in Brain Disorders)
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Open AccessArticle
Small Peptide Derived from SFRP5 Suppresses Melanogenesis by Inhibiting Wnt Activity
by
Yoon-Seo Choi, Jin-Gwen Hong, Dong-Young Lim, Min-Seo Kim, Sang-Hoon Park, Hee-Cheol Kang, Won-Sang Seo and Jongsung Lee
Curr. Issues Mol. Biol. 2024, 46(6), 5420-5435; https://doi.org/10.3390/cimb46060324 - 29 May 2024
Abstract
Melanocytes, located in the epidermis’ basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor
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Melanocytes, located in the epidermis’ basal layer, are responsible for melanin pigment production, crucial for skin coloration and protection against UV radiation-induced damage. Melanin synthesis is intricately regulated by various factors, including the Wnt signaling pathway, particularly mediated by the microphthalmia-associated transcription factor (MITF). While MITF is recognized as a key regulator of pigmentation, its regulation by the Wnt pathway remains poorly understood. This study investigates the role of Sfrp5pepD, a peptide antagonist of the Wnt signaling pathway, in modulating melanogenesis and its potential therapeutic implications for pigmentary disorders. To tackle this issue, we investigated smaller peptides frequently utilized in cosmetics or pharmaceuticals. Nevertheless, there is a significant scarcity of reports on peptides associated with melanin-related signal modulation or inhibiting melanin production. Results indicate that Sfrp5pepD effectively inhibits Wnt signaling by disrupting the interaction between Axin-1 and β-catenin, thus impeding downstream melanogenic processes. Additionally, Sfrp5pepD suppresses the interaction between MITF and β-catenin, inhibiting their nuclear translocation and downregulating melanogenic enzyme expression, ultimately reducing melanin production. These inhibitory effects are validated in cell culture models suggesting potential clinical applications for hyperpigmentation disorders. Overall, this study elucidates the intricate interplay between Wnt signaling and melanogenesis, highlighting Sfrp5pepD as a promising therapeutic agent for pigmentary disorders. Sfrp5pepD, with a molecular weight of less than 500 Da, is anticipated to penetrate the skin unlike SFRPs. This suggests a strong potential for their use as cosmetics or transdermal absorption agents. Additional investigation into its mechanisms and clinical significance is necessary to enhance its effectiveness in addressing melanin-related skin conditions.
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(This article belongs to the Section Molecular Medicine)
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Open AccessReview
Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation
by
Carlo Berrino and Aadilah Omar
Curr. Issues Mol. Biol. 2024, 46(6), 5397-5419; https://doi.org/10.3390/cimb46060323 - 29 May 2024
Abstract
The Sonic Hedgehog (Shh) signalling pathway plays a critical role in normal development and tissue homeostasis, guiding cell differentiation, proliferation, and survival. Aberrant activation of this pathway, however, has been implicated in the pathogenesis of various cancers, largely due to its role in
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The Sonic Hedgehog (Shh) signalling pathway plays a critical role in normal development and tissue homeostasis, guiding cell differentiation, proliferation, and survival. Aberrant activation of this pathway, however, has been implicated in the pathogenesis of various cancers, largely due to its role in regulating cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells with the ability to self-renew, differentiate, and initiate tumour growth, contributing significantly to tumorigenesis, recurrence, and resistance to therapy. This review focuses on the intricate activity of the Shh pathway within the context of CSCs, detailing the molecular mechanisms through which Shh signalling influences CSC properties, including self-renewal, differentiation, and survival. It further explores the regulatory crosstalk between the Shh pathway and other signalling pathways in CSCs, highlighting the complexity of this regulatory network. Here, we delve into the upstream regulators and downstream effectors that modulate Shh pathway activity in CSCs. This review aims to cast a specific focus on the role of the Shh pathway in CSCs, provide a detailed exploration of molecular mechanisms and regulatory crosstalk, and discuss current and developing inhibitors. By summarising key findings and insights gained, we wish to emphasise the importance of further elucidating the interplay between the Shh pathway and CSCs to develop more effective cancer therapies.
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(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Open AccessReview
Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies
by
Razmik Mirzayans
Curr. Issues Mol. Biol. 2024, 46(6), 5379-5396; https://doi.org/10.3390/cimb46060322 - 28 May 2024
Abstract
The many limitations of implementing anticancer strategies under the term “precision oncology” have been extensively discussed. While some authors propose promising future directions, others are less optimistic and use phrases such as illusion, hype, and false hypotheses. The reality is revealed by practicing
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The many limitations of implementing anticancer strategies under the term “precision oncology” have been extensively discussed. While some authors propose promising future directions, others are less optimistic and use phrases such as illusion, hype, and false hypotheses. The reality is revealed by practicing clinicians and cancer patients in various online publications, one of which has stated that “in the quest for the next cancer cure, few researchers bother to look back at the graveyard of failed medicines to figure out what went wrong”. The message is clear: Novel therapeutic strategies with catchy names (e.g., synthetic “lethality”) have not fulfilled their promises despite decades of extensive research and clinical trials. The main purpose of this review is to discuss key challenges in solid tumor therapy that surprisingly continue to be overlooked by the Nomenclature Committee on Cell Death (NCCD) and numerous other authors. These challenges include: The impact of chemotherapy-induced genome chaos (e.g., multinucleation) on resistance and relapse, oncogenic function of caspase 3, cancer cell anastasis (recovery from late stages of apoptosis), and pitfalls of ubiquitously used preclinical chemosensitivity assays (e.g., cell “viability” and tumor growth delay studies in live animals) that score such pro-survival responses as “lethal” events. The studies outlined herein underscore the need for new directions in the management of solid tumors.
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(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)
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Open AccessArticle
Association of Glycoprotein IIIa PlA1/A2 Polymorphism with Risk of Stroke: Updated Meta-Analysis
by
Camelia Alexandra Coadă, Mihai Lupu, Iulia Florea, Stella Di Constanzo, Sara Coluccelli and Ioan Şimon
Curr. Issues Mol. Biol. 2024, 46(6), 5364-5378; https://doi.org/10.3390/cimb46060321 - 28 May 2024
Abstract
Cardiovascular diseases are the main cause of death in the world, with ischemic heart disease (i.e., myocardial infarction) and cerebrovascular disease (i.e., stroke) taking the highest toll. Advances in diagnosis and treatment have led to a significant alleviation of ischemic complications, specifically in
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Cardiovascular diseases are the main cause of death in the world, with ischemic heart disease (i.e., myocardial infarction) and cerebrovascular disease (i.e., stroke) taking the highest toll. Advances in diagnosis and treatment have led to a significant alleviation of ischemic complications, specifically in the realm of pharmacotherapy and interventional devices, while pharmacogenomics has yet to be fully leveraged to improve the burden of disease. Atherothrombotic events might occur earlier or respond worse to treatment in patients with genetic variants of GP IIb/IIIa. Therefore, we aimed to quantitate the involvement of the PlA2 variant in the risk of cerebral stroke events. A systematic search and meta-analysis were performed by pooling the risks of individual studies. A total of 31 studies comprising 5985 stroke patients and 7886 controls were analyzed. A meta-analysis of four studies on hemorrhagic stroke patients showed no association with the PIA2 rs5918(C) polymorphism in both fixed-effect (OR = 0.90 95%CI [0.71; 1.14]; p = 0.398) and random-effect models (OR = 0.86 95%CI [0.62; 1.20]; p-value = 0.386). The power of this analysis was below <30%, indicating a limited ability to detect a true effect. An analysis of the 28 studies on ischemic stroke revealed a significant association with the PIA2 rs5918(C) allele in both fixed-effect (OR = 1.16 95%CI [1.06; 1.27]; p = 0.001) and random-effect models (OR = 1.20 95%CI [1.04; 1.38]; p-value = 0.012), with a power of >80%. The PIA2 allele was associated with an increased risk of ischemic stroke. No association was found with hemorrhagic stroke, most likely due to the small number of available studies, which resulted in a lack of power.
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(This article belongs to the Special Issue Cerebrovascular Diseases: From Pathogenesis to Treatment)
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Open AccessCommunication
Complete Mitogenome of “Pumpo” (Bos taurus), a Top Bull from a Peruvian Genetic Nucleus, and Its Phylogenetic Analysis
by
Richard Estrada, Deyanira Figueroa, Yolanda Romero, Wuesley Yusmein Alvarez-García, Diorman Rojas, Wigoberto Alvarado, Jorge L. Maicelo, Carlos Quilcate and Carlos I. Arbizu
Curr. Issues Mol. Biol. 2024, 46(6), 5352-5363; https://doi.org/10.3390/cimb46060320 - 28 May 2024
Abstract
The mitochondrial genome of Pumpo (Bos taurus), a prominent breed contributing to livestock farming, was sequenced using the Illumina HiSeq 2500 platform. Assembly and annotation of the mitochondrial genome were achieved through a multifaceted approach employing bioinformatics tools such as Trim
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The mitochondrial genome of Pumpo (Bos taurus), a prominent breed contributing to livestock farming, was sequenced using the Illumina HiSeq 2500 platform. Assembly and annotation of the mitochondrial genome were achieved through a multifaceted approach employing bioinformatics tools such as Trim Galore, SPAdes, and Geseq, followed by meticulous manual inspection. Additionally, analyses covering tRNA secondary structure and codon usage bias were conducted for comprehensive characterization. The 16,341 base pair mitochondrial genome comprises 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. Phylogenetic analysis places Pumpo within a clade predominantly composed of European cattle, reflecting its prevalence in Europe. This comprehensive study underscores the importance of mitochondrial genome analysis in understanding cattle evolution and highlights the potential of genetic improvement programs in livestock farming, thus contributing to enhanced livestock practices.
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(This article belongs to the Special Issue Mitochondrial Genome 2024)
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