Current Issues in Molecular Biology

15 pages, 1322 KiB

Open AccessReview

Ghrelin/GHSR System in Depressive Disorder: Pathologic Roles and Therapeutic Implications

by Xingli Pan, Yuxin Gao, Kaifu Guan, Jing Chen and Bingyuan Ji

Curr. Issues Mol. Biol. 2024, 46(7), 7324-7338; https://doi.org/10.3390/cimb46070434 (registering DOI) - 10 Jul 2024

Viewed by 160

Abstract

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, its pathologic mechanisms remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays [...] Read more.

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, its pathologic mechanisms remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays a dual role in experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, this hormone modifies signals connected to depression. The present review focuses on the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK, to produce antidepressant effects, given which it is expected to become a potential therapeutic target for the treatment of depression. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics in Brain Disorders)

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21 pages, 4258 KiB

Open AccessArticle

Lonicera japonica Thunb. Ethanol Extract Exerts a Protective Effect on Normal Human Gastric Epithelial Cells by Modulating the Activity of Tumor-Necrosis-Factor-α-Induced Inflammatory Cyclooxygenase 2/Prostaglandin E2 and Matrix Metalloproteinase 9

by Hsi-Lung Hsieh, Ming-Chin Yu, Yu-Chia Chang, Yi-Hsuan Wu, Kuo-Hsiung Huang and Ming-Ming Tsai

Curr. Issues Mol. Biol. 2024, 46(7), 7303-7323; https://doi.org/10.3390/cimb46070433 - 9 Jul 2024

Viewed by 146

Abstract

Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E₂ (PEG₂) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the [...] Read more.

Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E₂ (PEG₂) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric inflammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol extract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal human gastric mucosa epithelial cells (GES-1). The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE₂ and MMP-9 proteins induced by TNF-α to examine the anti-inflammatory properties of Lj extracts. The results indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG₂ and MMP-9 activity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflammation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG₂ and MMP-9 through the activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH exhibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation. Full article

(This article belongs to the Special Issue Bioactive Natural and Synthetic Saccharides against Human Diseases)

12 pages, 4039 KiB

Open AccessArticle

Application of Transcriptome-Based Gene Set Featurization for Machine Learning Model to Predict the Origin of Metastatic Cancer

by Yeonuk Jeong, Jinah Chu, Juwon Kang, Seungjun Baek, Jae-Hak Lee, Dong-Sub Jung, Won-Woo Kim, Yi-Rang Kim, Jihoon Kang and In-Gu Do

Curr. Issues Mol. Biol. 2024, 46(7), 7291-7302; https://doi.org/10.3390/cimb46070432 - 9 Jul 2024

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Abstract

Identifying the primary site of origin of metastatic cancer is vital for guiding treatment decisions, especially for patients with cancer of unknown primary (CUP). Despite advanced diagnostic techniques, CUP remains difficult to pinpoint and is responsible for a considerable number of cancer-related fatalities. [...] Read more.

Identifying the primary site of origin of metastatic cancer is vital for guiding treatment decisions, especially for patients with cancer of unknown primary (CUP). Despite advanced diagnostic techniques, CUP remains difficult to pinpoint and is responsible for a considerable number of cancer-related fatalities. Understanding its origin is crucial for effective management and potentially improving patient outcomes. This study introduces a machine learning framework, ONCOfind-AI, that leverages transcriptome-based gene set features to enhance the accuracy of predicting the origin of metastatic cancers. We demonstrate its potential to facilitate the integration of RNA sequencing and microarray data by using gene set scores for characterization of transcriptome profiles generated from different platforms. Integrating data from different platforms resulted in improved accuracy of machine learning models for predicting cancer origins. We validated our method using external data from clinical samples collected through the Kangbuk Samsung Medical Center and Gene Expression Omnibus. The external validation results demonstrate a top-1 accuracy ranging from 0.80 to 0.86, with a top-2 accuracy of 0.90. This study highlights that incorporating biological knowledge through curated gene sets can help to merge gene expression data from different platforms, thereby enhancing the compatibility needed to develop more effective machine learning prediction models. Full article

(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)

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33 pages, 580 KiB

Open AccessReview

The Impact of HIV and Parasite Single Infection and Coinfection on Telomere Length: A Systematic Review

by Engelinah D. Macamo, Zilungile L. Mkhize-Kwitshana, Julian Mthombeni and Pragalathan Naidoo

Curr. Issues Mol. Biol. 2024, 46(7), 7258-7290; https://doi.org/10.3390/cimb46070431 - 8 Jul 2024

Viewed by 128

Abstract

HIV and parasite infections accelerate biological aging, resulting in immune senescence, apoptosis and cellular damage. Telomere length is considered to be one of the most effective biomarkers of biological aging. HIV and parasite infection have been reported to shorten telomere length in the [...] Read more.

HIV and parasite infections accelerate biological aging, resulting in immune senescence, apoptosis and cellular damage. Telomere length is considered to be one of the most effective biomarkers of biological aging. HIV and parasite infection have been reported to shorten telomere length in the host. This systematic review aimed to highlight work that explored the influence of HIV and parasite single infections and coinfection on telomere length. Using specific keywords related to the topic of interest, an electronic search of several online databases (Google Scholar, Web of Science, Scopus, Science Direct and PubMed) was conducted to extract eligible articles. The association between HIV infection or parasite infection and telomere length and the association between HIV and parasite coinfection and telomere length were assessed independently. The studies reported were mostly conducted in the European countries. Of the 42 eligible research articles reviewed, HIV and parasite single infections were independently associated with telomere length shortening. Some studies found no association between antiretroviral therapy (ART) and telomere length shortening, while others found an association between ART and telomere length shortening. No studies reported on the association between HIV and parasite coinfection and telomere length. HIV and parasite infections independently accelerate telomere length shortening and biological aging. It is possible that coinfection with HIV and parasites may further accelerate telomere length shortening; however, this is a neglected field of research with no reported studies to date. Full article

(This article belongs to the Special Issue Human and Animal Infectious Diseases: Prevention, Diagnosis, and Treatment)

19 pages, 1840 KiB

Open AccessReview

The Latest Look at PDT and Immune Checkpoints

by David Aebisher, Agnieszka Przygórzewska and Dorota Bartusik-Aebisher

Curr. Issues Mol. Biol. 2024, 46(7), 7239-7257; https://doi.org/10.3390/cimb46070430 - 8 Jul 2024

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Abstract

Photodynamic therapy (PDT) can not only directly eliminate cancer cells, but can also stimulate antitumor immune responses. It also affects the expression of immune checkpoints. The purpose of this review is to collect, analyze, and summarize recent news about PDT and immune checkpoints, [...] Read more.

Photodynamic therapy (PDT) can not only directly eliminate cancer cells, but can also stimulate antitumor immune responses. It also affects the expression of immune checkpoints. The purpose of this review is to collect, analyze, and summarize recent news about PDT and immune checkpoints, along with their inhibitors, and to identify future research directions that may enhance the effectiveness of this approach. A search for research articles published between January 2023 and March 2024 was conducted in PubMed/MEDLINE. Eligibility criteria were as follows: (1) papers describing PDT and immune checkpoints, (2) only original research papers, (3) only papers describing new reports in the field of PDT and immune checkpoints, and (4) both in vitro and in vivo papers. Exclusion criteria included (1) papers written in a language other than Polish or English, (2) review papers, and (3) papers published before January 2023. 24 papers describing new data on PDT and immune checkpoints have been published since January 2023. These included information on the effects of PDT on immune checkpoints, and attempts to associate PDT with ICI and with other molecules to modulate immune checkpoints, improve the immunosuppressive environment of the tumor, and resolve PDT-related problems. They also focused on the development of new nanoparticles that can improve the delivery of photosensitizers and drugs selectively to the tumor. The effect of PDT on the level of immune checkpoints and the associated activity of the immune system has not been fully elucidated further, and reports in this area are divergent, indicating the complexity of the interaction between PDT and the immune system. PDT-based strategies have been shown to have a beneficial effect on the delivery of ICI to the tumor. The utility of PDT in enhancing the induction of the antitumor response by participating in the triggering of immunogenic cell death, the exposure of tumor antigens, and the release of various alarm signals that together promote the activation of dendritic cells and other components of the immune system has also been demonstrated, with the result that PDT can enhance the antitumor immune response induced by ICI therapy. PDT also enables multifaceted regulation of the tumor’s immunosuppressive environment, as a result of which ICI therapy has the potential to achieve better antitumor efficacy. The current review has presented evidence of PDT’s ability to modulate the level of immune checkpoints and the effectiveness of the association of PDT with ICIs and other molecules in inducing an effective immune response against cancer cells. However, these studies are at an early stage and many more observations need to be made to confirm their efficacy. The new research directions indicated may contribute to the development of further strategies. Full article

(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2024)

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20 pages, 2118 KiB

Open AccessCommunication

Preliminary Study on the Restoration of the Phospholipid Profile in Serum from Patients with COVID-19 by Treatment with Vitamin E

by María Elena Soto, Linaloe Manzano-Pech, Verónica Guarner-Lans, Adrían Palacios-Chavarría, Rafael Ricardo Valdez-Vázquez, Raúl Martínez-Memije, Mohammed El-Hafidi, Félix Leao Rodríguez-Fierros and Israel Pérez-Torres

Curr. Issues Mol. Biol. 2024, 46(7), 7219-7238; https://doi.org/10.3390/cimb46070429 - 8 Jul 2024

Viewed by 380

Abstract

SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative [...] Read more.

SARS-CoV-2 is an obligatory intracellular pathogen that requires a lipid bilayer membrane for its transport to build its nucleocapsid envelope and fuse with the host cell. The biological membranes are constituted by phospholipids (PLs), and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFAs), fatty acids of the phospholipids (FAPLs), total phospholipids (TPLs), 8-isoprostane, thromboxane B₂ (TXB₂), prostaglandins (PGE₂ and 6-keto-PGF1_α), interleukin-6 (IL-6), and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HSs). COVID-19 patients showed a decrease in Vit E, TPLs, FAPLs, and TFAs in serum in comparison to HSs (p ≤ 0.01), and Vit E treatment restored their levels (p ≤ 0.04). Likewise, there was an increase in IL-6 and CRP in COVID-19 patients in comparison with HSs (p ≤ 0.001), and treatment with Vit E decreased their levels (p ≤ 0.001). Treatment with Vit E as monotherapy can contribute to restoring the modified FA profile of the PLs in the SARS-CoV-2 infection, and this leads to a decrease in lipid peroxidation, OS, and the inflammatory process. Full article

(This article belongs to the Section Molecular Medicine)

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32 pages, 2057 KiB

Open AccessArticle

The Effect of Removal of External Proteins PsbO, PsbP and PsbQ on Flash-Induced Molecular Oxygen Evolution and Its Biphasicity in Tobacco PSII

by Sonia Krysiak and Kvetoslava Burda

Curr. Issues Mol. Biol. 2024, 46(7), 7187-7218; https://doi.org/10.3390/cimb46070428 - 8 Jul 2024

Viewed by 314

Abstract

The oxygen evolution within photosystem II (PSII) is one of the most enigmatic processes occurring in nature. It is suggested that external proteins surrounding the oxygen-evolving complex (OEC) not only stabilize it and provide an appropriate ionic environment but also create water channels, [...] Read more.

The oxygen evolution within photosystem II (PSII) is one of the most enigmatic processes occurring in nature. It is suggested that external proteins surrounding the oxygen-evolving complex (OEC) not only stabilize it and provide an appropriate ionic environment but also create water channels, which could be involved in triggering the ingress of water and the removal of O₂ and protons outside the system. To investigate the influence of these proteins on the rate of oxygen release and the efficiency of OEC function, we developed a measurement protocol for the direct measurement of the kinetics of oxygen release from PSII using a Joliot-type electrode. PSII-enriched tobacco thylakoids were used in the experiments. The results revealed the existence of slow and fast modes of oxygen evolution. This observation is model-independent and requires no specific assumptions about the initial distribution of the OEC states. The gradual removal of exogenous proteins resulted in a slowdown of the rapid phase (~ms) of O₂ release and its gradual disappearance while the slow phase (~tens of ms) accelerated. The role of external proteins in regulating the biphasicity and efficiency of oxygen release is discussed based on observed phenomena and current knowledge. Full article

(This article belongs to the Topic Metalloproteins and Metalloenzymes)

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18 pages, 5410 KiB

Open AccessArticle

Isolation of a Virulent Clostridium perfringens Strain from Elaphurus davidianus and Characterization by Whole-Genome Sequence Analysis

by Zhao Zhang, Xiao Wang, Siyuan Li, Yuhang Fu, Yan Li, Shah Nawaz, Jing Chen, Guoxiang Yang, Jiakui Li and Daoliang Shi

Curr. Issues Mol. Biol. 2024, 46(7), 7169-7186; https://doi.org/10.3390/cimb46070427 - 8 Jul 2024

Viewed by 347

Abstract

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there [...] Read more.

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there is an increasing trend in conducting whole-genome analysis of C. perfringens strains originating from pigs and chickens, whereas fewer studies have been undertaken on Elaphurus davidianus-originating strains at the whole-genome level. Our laboratory has identified and isolated five C. perfringens type A from affected Elaphurus davidianus. The current study identified the most potent strain of C. perfringens, which originated from Elaphurus davidianus, and sequenced its genome to reveal virulence genes and pathogenicity. Our findings show that strain CX1-4 exhibits the highest levels of phospholipase activity, hemolytic activity, and mouse toxicity compared to the other four isolated C. perfringens type A strains. The chromosome sequence length of the CX1-4 strain was found to be 3,355,389 bp by complete genome sequencing. The current study unveils the genomic characteristics of C. perfringens type A originating from Elaphurus davidianus. It provides a core foundation for further investigation regarding the prevention and treatment of such infectious diseases in Elaphurus davidianus. Full article

(This article belongs to the Collection Feature Papers Collection in Molecular Microbiology)

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22 pages, 1108 KiB

Open AccessReview

Unveiling the Potential of Sulfur-Containing Gas Signaling Molecules in Acute Lung Injury: A Promising Therapeutic Avenue

by Xutao Sun, Caiyun Mao, Jiaxin Wang, Siyu Wu, Ying Qu, Ying Xie, Fengqi Sun, Deyou Jiang and Yunjia Song

Curr. Issues Mol. Biol. 2024, 46(7), 7147-7168; https://doi.org/10.3390/cimb46070426 - 7 Jul 2024

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Abstract

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are pulmonary conditions that cause significant morbidity and mortality. The common etiologies of these conditions include pneumonia, pulmonary contusion, fat embolism, smoke inhalation, sepsis, shock, and acute pancreatitis. Inflammation, [...] Read more.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are pulmonary conditions that cause significant morbidity and mortality. The common etiologies of these conditions include pneumonia, pulmonary contusion, fat embolism, smoke inhalation, sepsis, shock, and acute pancreatitis. Inflammation, oxidative stress, apoptosis, and autophagy are key pathophysiological mechanisms underlying ALI. Hydrogen sulfide (H₂S) and sulfur dioxide (SO₂) are sulfur-containing gas signaling molecules that can mitigate these pathogenic processes by modulating various signaling pathways, such as toll-like receptor 4 (TLR4)/nod-like receptor protein 3 (NLRP3), extracellular signal-regulating protein kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB), thereby conferring protection against ALI. Given the limited clinical effectiveness of prevailing ALI treatments, investigation of the modulation of sulfur-containing gas signaling molecules (H₂S and SO₂) in ALI is imperative. This article presents an overview of the regulatory pathways of sulfur-containing gas signaling molecules in ALI animal models induced by various stimuli, such as lipopolysaccharide, gas inhalation, oleic acid, and ischemia-reperfusion. Furthermore, this study explored the therapeutic prospects of diverse H₂S and SO₂ donors for ALI, stemming from diverse etiologies. The aim of the present study was to establish a theoretical framework, in order to promote the new treatment of ALI. Full article

(This article belongs to the Section Molecular Medicine)

13 pages, 2029 KiB

Open AccessReview

Mechanobiology in Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity

by Emily L. Rudolph and LiKang Chin

Curr. Issues Mol. Biol. 2024, 46(7), 7134-7146; https://doi.org/10.3390/cimb46070425 - 7 Jul 2024

Viewed by 303

Abstract

With the ongoing obesity epidemic, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to rise and necessitates a greater understanding of how the disease proceeds from benign excess lipid in hepatocytes to liver fibrosis and eventually to liver cancer. MASLD [...] Read more.

With the ongoing obesity epidemic, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to rise and necessitates a greater understanding of how the disease proceeds from benign excess lipid in hepatocytes to liver fibrosis and eventually to liver cancer. MASLD is caused, at least in part, by hepatocytes’ storage of free fatty acids (FAs) that dysfunctional adipocytes are no longer able to store, and therefore, MASLD is a disease that involves both the liver and adipose tissues. The disease progression is not only facilitated by biochemical signals, but also by mechanical cues such as the increase in stiffness often seen with fibrotic fatty livers. The change in stiffness and accumulation of excess lipid droplets impact the ability of a cell to mechanosense and mechanotranduce, which perpetuates the disease. A mechanosensitive protein that is largely unexplored and could serve as a potential therapeutic target is the intermediate filament vimentin. In this review, we briefly summarize the recent research on hepatocyte and adipocyte mechanobiology and provide a synopsis of studies on the varied, and sometimes contradictory, roles of vimentin. This review is intended to benefit and encourage future studies on hepatocyte and adipocyte mechanobiology in the context of MASLD and obesity. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Nonalcoholic Fatty Liver Disease)

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20 pages, 1449 KiB

Open AccessArticle

Secondary Analysis of Human Bulk RNA-Seq Dataset Suggests Potential Mechanisms for Letrozole Resistance in Estrogen-Positive (ER+) Breast Cancer

by Lincoln Sutherland, Jacob Lang, Norberto Gonzalez-Juarbe and Brett E. Pickett

Curr. Issues Mol. Biol. 2024, 46(7), 7114-7133; https://doi.org/10.3390/cimb46070424 - 6 Jul 2024

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Abstract

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole, which inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. The increase in Letrozole resistance poses [...] Read more.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole, which inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. The increase in Letrozole resistance poses a unique problem for patients. To better understand the underlying molecular mechanism(s) of Letrozole resistance, we reanalyzed transcriptomic data by comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two significant differentially expressed genes (DEGs) between these patient cohorts, with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 gene products as being the top mechanistic transcriptional markers for ER+ treatment resistance. Many of the significant DEGs that we identified play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified are novel in the context of ER+ breast cancer. Many of the genes that we identified warrant further research to elucidate the more specific molecular mechanisms of Letrozole resistance in this patient population and could potentially be used as prognostic markers with further wet lab validation. We anticipate that these findings could contribute to improved detection and therapeutic outcomes in aromatase-resistant ER+ breast cancer patients. Full article

(This article belongs to the Special Issue The Significance of Transcription Factors, miRNAs, and lncRNAs in Anticancer Drug Development)

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17 pages, 2548 KiB

Open AccessReview

MicroRNAs as Regulators of Radiation-Induced Oxidative Stress

by Branislav Kura, Patricia Pavelkova, Barbora Kalocayova, Margita Pobijakova and Jan Slezak

Curr. Issues Mol. Biol. 2024, 46(7), 7097-7113; https://doi.org/10.3390/cimb46070423 - 6 Jul 2024

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Abstract

microRNAs (miRNAs) represent small RNA molecules involved in the regulation of gene expression. They are implicated in the regulation of diverse cellular processes ranging from cellular homeostasis to stress responses. Unintended irradiation of the cells and tissues, e.g., during medical uses, induces various [...] Read more.

microRNAs (miRNAs) represent small RNA molecules involved in the regulation of gene expression. They are implicated in the regulation of diverse cellular processes ranging from cellular homeostasis to stress responses. Unintended irradiation of the cells and tissues, e.g., during medical uses, induces various pathological conditions, including oxidative stress. miRNAs may regulate the expression of transcription factors (e.g., nuclear factor erythroid 2 related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor suppressor protein p53) and other redox-sensitive genes (e.g., mitogen-activated protein kinase (MAPKs), sirtuins (SIRTs)), which trigger and modulate cellular redox signaling. During irradiation, miRNAs mainly act with reactive oxygen species (ROS) to regulate the cell fate. Depending on the pathway involved and the extent of oxidative stress, this may lead to cell survival or cell death. In the context of radiation-induced oxidative stress, miRNA-21 and miRNA-34a are among the best-studied miRNAs. miRNA-21 has been shown to directly target superoxide dismutase (SOD), or NF-κB, whereas miRNA-34a is a direct regulator of NADPH oxidase (NOX), SIRT1, or p53. Understanding the mechanisms underlying radiation-induced injury including the involvement of redox-responsive miRNAs may help to develop novel approaches for modulating the cellular response to radiation exposure. Full article

(This article belongs to the Special Issue Molecular Research on Free Radicals and Oxidative Stress)

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11 pages, 1098 KiB

Open AccessReview

Mechanism of DAPK1 for Regulating Cancer Stem Cells in Thyroid Cancer

by Mi-Hyeon You

Curr. Issues Mol. Biol. 2024, 46(7), 7086-7096; https://doi.org/10.3390/cimb46070422 - 5 Jul 2024

Viewed by 211

Abstract

Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca²⁺/CaM)-dependent serine/threonine (Ser/Thr) protein kinase and is characteristically downregulated in metastatic cancer. Several studies showed that DAPK1 is involved in both the early and late stages of cancer. DAPK1 downregulation is elaborately controlled [...] Read more.

Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca²⁺/CaM)-dependent serine/threonine (Ser/Thr) protein kinase and is characteristically downregulated in metastatic cancer. Several studies showed that DAPK1 is involved in both the early and late stages of cancer. DAPK1 downregulation is elaborately controlled by epigenetic, transcriptional, posttranscriptional, and posttranslational processes. DAPK1 is known to regulate not only cancer cells but also stromal cells. Recent studies showed that DAPK1 was involved not only in tumor suppression but also in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation in colon and thyroid cancers. CSCs are major factors in determining cancer aggressiveness in cancer metastasis and treatment prognosis by influencing EMT. However, the molecular mechanism involved in the regulation of cancer cells by DAPK1 remains unclear. In particular, little is known about the existence of CSCs and how they are regulated in papillary thyroid carcinoma (PTC) among thyroid cancers. In this review, we describe the molecular mechanism of CSC regulation by DAPK1 in PTC progression. Full article

(This article belongs to the Special Issue The Significance of Transcription Factors, miRNAs, and lncRNAs in Anticancer Drug Development)

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21 pages, 5275 KiB

Open AccessArticle

Expression and Functional Analysis of Immuno-Micro-RNAs mir-146a and mir-326 in Colorectal Cancer

by Ovidiu Farc, Liviuta Budisan, Florin Zaharie, Roman Țăulean, Dan Vălean, Elena Talvan, Ioana Berindan Neagoe, Oana Zănoagă, Cornelia Braicu and Victor Cristea

Curr. Issues Mol. Biol. 2024, 46(7), 7065-7085; https://doi.org/10.3390/cimb46070421 - 5 Jul 2024

Viewed by 305

Abstract

Micro-RNAs (miRNAs) are non-coding RNAs with importance in the development of cancer. They are involved in both tumor development and immune processes in tumors. The present study aims to characterize the behavior of two miRNAs, the proinflammatory miR-326-5p and the anti-inflammatory miR-146a-5p, in [...] Read more.

Micro-RNAs (miRNAs) are non-coding RNAs with importance in the development of cancer. They are involved in both tumor development and immune processes in tumors. The present study aims to characterize the behavior of two miRNAs, the proinflammatory miR-326-5p and the anti-inflammatory miR-146a-5p, in colorectal cancer (CRC), to decipher the mechanisms that regulate their expression, and to study potential applications. Tissue levels of miR-326-5p and miR-146a-5p were determined by qrt-PCR (real-time quantitative reverse transcription polymerase chain reaction) in 45 patients with colorectal cancer in tumoral and normal adjacent tissue. Subsequent bioinformatic analysis was performed to characterize the transcriptional networks that control the expression of the two miRNAs. The biomarker potential of miRNAs was assessed. The expression of miR-325-5p and miR-146a-5p was decreased in tumors compared to normal tissue. The two miRNAs are regulated through a transcriptional network, which originates in the inflammatory and proliferative pathways and regulates a set of cellular functions related to immunity, proliferation, and differentiation. The miRNAs coordinate distinct modules in the network. There is good biomarker potential of miR-326 with an AUC (Area under the curve) of 0.827, 0.911 sensitivity (Sn), and 0.689 specificity (Sp), and of the combination miR-326-miR-146a, with an AUC of 0.845, Sn of 0.75, and Sp of 0.89. The miRNAs are downregulated in the tumor tissue. They are regulated by a transcriptional network in which they coordinate distinct modules. The structure of the network highlights possible therapeutic approaches. MiR-326 and the combination of the two miRNAs may serve as biomarkers in CRC. Full article

(This article belongs to the Special Issue The Significance of Transcription Factors, miRNAs, and lncRNAs in Anticancer Drug Development)

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17 pages, 1104 KiB

Open AccessReview

Unraveling the Immune Microenvironment in Diffuse Large B-Cell Lymphoma: Prognostic and Potential Therapeutic Implications

by Epameinondas Koumpis, Alexandra Papoudou-Bai, Konstantina Papathanasiou, Evangelos Kolettas, Panagiotis Kanavaros and Eleftheria Hatzimichael

Curr. Issues Mol. Biol. 2024, 46(7), 7048-7064; https://doi.org/10.3390/cimb46070420 - 5 Jul 2024

Viewed by 737

Abstract

Diffuse large B cell lymphoma (DLBCL) is a multifaceted condition characterized by significant diversity in its molecular and pathological subtypes and clinical manifestation. Despite the progress made in the treatment of DLBCL through the development of novel drugs, an estimated one-third of patients [...] Read more.

Diffuse large B cell lymphoma (DLBCL) is a multifaceted condition characterized by significant diversity in its molecular and pathological subtypes and clinical manifestation. Despite the progress made in the treatment of DLBCL through the development of novel drugs, an estimated one-third of patients encounter relapse or acquire refractory disease. The tumor microenvironment (TME) of DLBCL, a complex network consisting of cellular and noncellular components that engage in interactions with the tumor, is a parameter that is gaining increasing attention. The TME comprises both the immune and nonimmune microenvironments. The immune microenvironment comprises natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), neutrophils, myeloid-derived suppressor cells (MDSCs), and T and B lymphocytes. The nonimmune microenvironment consists of the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), mesenchymal stromal cells, and other molecules that are secreted. Despite ongoing research, the exact impact of these components and their interaction on the progression of the disease remains elusive. A comprehensive review of significant discoveries concerning the cellular and noncellular constituents, molecular characteristics, and treatment response and prognosis of the TME in DLBCL, as well as the potential targeting of the TME with novel therapeutic approaches, is provided in this article. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy, 2nd Edition)

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16 pages, 3147 KiB

Open AccessArticle

Comparison of the Proteome of Huh7 Cells Transfected with Hepatitis B Virus Subgenotype A1, with or without G1862T

by Kiyasha Padarath, Aurélie Deroubaix, Previn Naicker, Stoyan Stoychev and Anna Kramvis

Curr. Issues Mol. Biol. 2024, 46(7), 7032-7047; https://doi.org/10.3390/cimb46070419 - 4 Jul 2024

Viewed by 329

Abstract

HBeAg is a non-structural, secreted protein of hepatitis B virus (HBV). Its p25 precursor is post-translationally modified in the endoplasmic reticulum. The G1862T precore mutation leads to the accumulation of P25 in the endoplasmic reticulum and activation of unfolded protein response. Using mass [...] Read more.

HBeAg is a non-structural, secreted protein of hepatitis B virus (HBV). Its p25 precursor is post-translationally modified in the endoplasmic reticulum. The G1862T precore mutation leads to the accumulation of P25 in the endoplasmic reticulum and activation of unfolded protein response. Using mass spectrometry, comparative proteome profiling of Huh-7 cells transfected with wildtype (WT) or G1862T revealed significantly differentially expressed proteins resulting in 12 dysregulated pathways unique to WT-transfected cells and 7 shared between cells transfected with either WT or G1862T. Except for the p38 MAPK signalling pathway, WT showed a higher number of DEPs than G1862T-transfected cells in all remaining six shared pathways. Two signalling pathways: oxidative stress and cell cycle signalling were differentially expressed only in cells transfected with G1862T. Fifteen pathways were dysregulated in G1862T-transfected cells compared to WT. The 15 dysregulated pathways were involved in the following processes: MAPK signalling, DNA synthesis and methylation, and extracellular matrix organization. Moreover, proteins involved in DNA synthesis signalling (replication protein A (RPA) and DNA primase (PRIM2)) were significantly upregulated in G1862T compared to WT. This upregulation was confirmed by mRNA quantification of both genes and immunofluorescent confocal microscopy for RPA only. The dysregulation of the pathways involved in these processes may lead to immune evasion, persistence, and uncontrolled proliferation, which are hallmarks of cancer. Full article

(This article belongs to the Special Issue Research on Virus-Induced Cellular and Molecular Responses)

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31 pages, 2020 KiB

Open AccessReview

Beyond the Coagulation Cascade: Vitamin K and Its Multifaceted Impact on Human and Domesticated Animal Health

by Rebecka A. Sadler, Anna K. Shoveller, Umesh K. Shandilya, Armen Charchoglyan, Lauraine Wagter-Lesperance, Byram W. Bridle, Bonnie A. Mallard and Niel A. Karrow

Curr. Issues Mol. Biol. 2024, 46(7), 7001-7031; https://doi.org/10.3390/cimb46070418 - 4 Jul 2024

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Abstract

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule’s importance to human health includes but is not limited to [...] Read more.

Vitamin K (VK) is an essential micronutrient impacting many systems in the body. This lipid-soluble vitamin is found in various plant and animal products and is absorbed via the lymphatic system. This biomolecule’s importance to human health includes but is not limited to its promotion of brain, cardiovascular, bone, and immune functions. These biological properties are also necessary for maintaining domesticated animal health. The synergistic impact of both VK and vitamin D (VD) maximizes these health benefits, specifically for the circulatory and skeletal systems. This manuscript reviews VK’s properties, molecular structures, nutrikinetics, mechanisms of action, daily requirements, safety in supplemental form, biomarkers used for its detection, and impacts on various organs. The purpose of synthesizing this information is to evaluate the potential uses of VK for the treatment or prevention of diseases. Full article

(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)

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15 pages, 1869 KiB

Open AccessArticle

In Vitro Evaluation of DNA Damage Induction by Silver (Ag), Gold (Au), Silica (SiO₂), and Aluminum Oxide (Al₂O₃) Nanoparticles in Human Peripheral Blood Mononuclear Cells

by Milda Babonaitė, Emilija Striogaitė, Goda Grigorianaitė and Juozas Rimantas Lazutka

Curr. Issues Mol. Biol. 2024, 46(7), 6986-7000; https://doi.org/10.3390/cimb46070417 - 4 Jul 2024

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Abstract

Nanoparticles (NPs) are increasingly applied in a wide range of technological and medical applications. While their use offers numerous benefits, it also raises concerns regarding their safety. Therefore, understanding their cytotoxic effects and DNA-damaging properties is crucial for ensuring the safe application of [...] Read more.

Nanoparticles (NPs) are increasingly applied in a wide range of technological and medical applications. While their use offers numerous benefits, it also raises concerns regarding their safety. Therefore, understanding their cytotoxic effects and DNA-damaging properties is crucial for ensuring the safe application of NPs. In this study, DNA-damaging properties of PVP-coated silver, silica, aluminum oxide (13 nm and 50 nm), and gold (5 nm and 40 nm) NPs in human peripheral blood mononuclear cells (PBMCs) were investigated. NPs‘ internalization and induction of reactive oxygen species were evaluated using flow cytometry. Cytotoxic properties were determined using a dual acridine orange/ethidium bromide staining technique while DNA-damaging properties were assessed using an alkaline comet assay. We observed that Ag, SiO₂, and both sizes of Al₂O₃ NPs were efficiently internalized by human PBMCs, but only PVP-AgNPs (at 10–30 µg/mL) and SiO₂ NPs (at concentrations > 100 µg/mL) induced significant DNA damage after a 24 h exposure. In contrast, the uptake of both sizes of gold nanoparticles was limited, though they were able to cause significant DNA damage after a 3 h exposure. These findings highlight the different responses of human PBMCs to various NPs, emphasizing the importance of their size, composition, and internalization rates in nanotoxicology testing. Full article

(This article belongs to the Special Issue Effects of Nanoparticles on Living Organisms 2.0)

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25 pages, 925 KiB

Open AccessReview

Conformational Alterations of the Cell Surface of Monomeric and Dimeric β2m-Free HLA-I (Proto-HLA) May Enable Novel Immune Functions in Health and Disease

by Mepur H. Ravindranath, Narendranath M. Ravindranath, Carly J. Amato-Menker, Fatiha El Hilali and Edward J. Filippone

Curr. Issues Mol. Biol. 2024, 46(7), 6961-6985; https://doi.org/10.3390/cimb46070416 - 4 Jul 2024

Viewed by 564

Abstract

Human leukocyte antigens (HLAs) are polymorphic glycoproteins expressed on the cell surface of nucleated cells and consist of two classes, HLA class I and HLA class II. In contrast, in mice, these molecules, known as H-2, are expressed on both nucleated cells and [...] Read more.

Human leukocyte antigens (HLAs) are polymorphic glycoproteins expressed on the cell surface of nucleated cells and consist of two classes, HLA class I and HLA class II. In contrast, in mice, these molecules, known as H-2, are expressed on both nucleated cells and erythrocytes. HLA-I molecules (Face-1) are heterodimers consisting of a polypeptide heavy chain (HC) and a light chain, B2-microglobulin (B2m). The heterodimers bind to antigenic peptides and present them to the T-cell receptors of CD8+ cytotoxic T lymphocytes. The HCs can also independently emerge on the cell surface as B2m-free HC monomers without peptides (Face-2). Early investigators suggested that the occurrence of B2m-free HCs on the cell surface resulted from the dissociation of B2m from Face-1. However, others documented the independent emergence of B2m-free HCs (Face-2) from the endoplasmic reticulum (ER) to the cell surface. The clustering of such HC molecules on either the cell surface or on exosomes resulted in the dimerization of B2m-free HCs to form homodimers (if the same allele, designated as Face-3) or heterodimers (if different alleles, designated as Face-4). Face-2 occurs at low levels on the cell surface of several normal cells but is upregulated on immune cells upon activation by proinflammatory cytokines and other agents such as anti-CD3 antibodies, phytohemagglutinin, and phorbol myristate acetate. Their density on the cell surface remains high as long as the cells remain activated. After activation-induced upregulation, Face-2 molecules undergo homo- and heterodimerization (Face-3 and Face-4). Observations made on the structural patterns of HCs and their dimerization in sharks, fishes, and tetrapod species suggest that the formation of B2m-free HC monomers and dimers is a recapitalization of a phylogenetically conserved event, befitting the term Proto-HLA for the B2m-free HCs. Spontaneous arthritis occurs in HLA-B27+ mice lacking B2m (HLA-B27+ B2m−/−) but not in HLA-B27+ B2m+/+ mice. Anti-HC-specific monoclonal antibodies (mAbs) delay disease development. Some HLA-I polyreactive mAbs (MEM series) used for immunostaining confirm the existence of B2m-free variants in several cancer cells. The conformational alterations that occur in the B2m-free HCs enable them to interact with several inhibitory and activating receptors of cellular components of the innate (natural killer (NK) cells) and adaptive (T and B cells) immune systems. The NK cells express killer immunoglobulin-like receptors (KIRs), whereas leukocytes (T and B lymphocytes, monocytes/macrophages, and dendritic cells) express leukocyte immunoglobulin-like receptors (LILRs). The KIRs and LILRs include activating and inhibitory members within their respective groups. This review focuses on the interaction of KIRs and LILRs with B2m-free HC monomers and dimers in patients with spondylarthritis. Several investigations reveal that the conformational alterations occurring in the alpha-1 and alpha-2 domains of B2m-free HCs may facilitate immunomodulation by their interaction with KIR and LILR receptors. This opens new avenues to immunotherapy of autoimmune diseases and even human cancers that express B2m-free HCs. Full article

(This article belongs to the Special Issue Protein Domains: Structure and Molecular Function)

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1 pages, 163 KiB

Open AccessCorrection

Correction: Sundaraj et al. Cloning, Expression and Functional Characterization of a Novel α-Humulene Synthase, Responsible for the Formation of Sesquiterpene in Agarwood Originating from Aquilaria malaccensis. Curr. Issues Mol. Biol. 2023, 45, 8989–9002

by Yasotha Sundaraj, Hasdianty Abdullah, Nima Ghahremani Nezhad, Afiq Adham Abd Rasib, Roohaida Othman, Kenneth Francis Rodrigues, Suriana Sabri and Syarul Nataqain Baharum

Curr. Issues Mol. Biol. 2024, 46(7), 6960; https://doi.org/10.3390/cimb46070415 - 4 Jul 2024

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Abstract

Afiq Adham Abd Rasib and Roohaida Othman were not included as authors in the original publication [...] Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

9 pages, 289 KiB

Open AccessArticle

ADRB2 and ADCY9 Sequence Variations in Brazilian Asthmatic Patients

by Viviane da C. Silva, Raquel L. de F. Teixeira, Rebecca E. E. N. O. do Livramento, Márcia Q. P. Lopes, Thyago Leal-Calvo, José E. Filho, Márcia B. V. Luduvice, Lilian de C. Rodrigues, Marcello Bossois, Patricia F. Schlinkert, Anderson S. Neves, Philip N. Suffys, José Roberto Lapa e Silva and Adalberto R. Santos

Curr. Issues Mol. Biol. 2024, 46(7), 6951-6959; https://doi.org/10.3390/cimb46070414 - 4 Jul 2024

Viewed by 328

Abstract

Asthma is a chronic inflammatory respiratory condition, characterized by variable airflow limitation, leading to clinical symptoms such as dyspnea and chest tightness. These symptoms result from an underlying inflammatory process. The β2 agonists are bronchodilators prescribed for the relief of the disease. Nevertheless, [...] Read more.

Asthma is a chronic inflammatory respiratory condition, characterized by variable airflow limitation, leading to clinical symptoms such as dyspnea and chest tightness. These symptoms result from an underlying inflammatory process. The β2 agonists are bronchodilators prescribed for the relief of the disease. Nevertheless, their efficacy exhibits substantial interindividual variability. Currently, there is widespread recognition of the association between specific genetic variants, predominantly located within the ADRB2 and ADCY9 genes and their efficacy. This association, usually represented by the presence of non-synonymous single nucleotide polymorphisms (SNPs) have a strong impact in the protein functionality. The prevalence of these mutations varies based on the ethnic composition of the population and thus understanding the profiles of variability in different populations would contribute significantly to standardizing the use of these medications. In this study, we conducted a sequence-based genotyping of the relevant SNPs within the ADRB2 and ADCY9 genes in patients undergoing treatment with bronchodilators and/or corticosteroids at two healthcare facilities in the state of Rio de Janeiro, Brazil. We investigated the presence of c.46A>G, c.79C>G, c.252G>A, and c.491C>T SNPs within the ADRB2, and c.1320018 A>G within the ADCY9. Our results were in line with existing literature data with both for individuals in Brazil and Latin American. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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Open AccessArticle

Association between Skin Carotenoid Levels and Cognitive Impairment Screened by Mini-Cog in Patients with Glaucoma

by Yuji Takayanagi, Yoichi Kadoh, Junichi Sasaki, Akira Obana and Masaki Tanito

Curr. Issues Mol. Biol. 2024, 46(7), 6940-6950; https://doi.org/10.3390/cimb46070413 - 3 Jul 2024

Viewed by 319

Abstract

Carotenoids, having strong antioxidant properties, have been associated with neurodegenerative conditions like dementia and glaucoma, characterized by neuronal loss leading to cognitive and visual dysfunction. Therefore, carotenoids have attracted attention as factors predictive of the onset and progression of these neurodegenerative diseases. However, [...] Read more.

Carotenoids, having strong antioxidant properties, have been associated with neurodegenerative conditions like dementia and glaucoma, characterized by neuronal loss leading to cognitive and visual dysfunction. Therefore, carotenoids have attracted attention as factors predictive of the onset and progression of these neurodegenerative diseases. However, the impact of carotenoids on cognitive impairment and glaucomatous visual field defects remains unexplored. We conducted a retrospective, observational clinical study to investigate the association between skin carotenoid (SC) levels and cognitive impairment, as screened by the Mini-Cog test, in glaucoma patients. The study included 406 participants and 812 eyes were examined (average age: 69.7 ± 11.4 years; 228 men, 178 women) with various types of glaucoma: primary open angle (57.6%), exfoliation (18.6%), and other types (23.8%). SC levels were estimated via pressure-mediated reflection spectroscopy. Mixed-effects regression models were utilized to examine the relationship between SC levels, visual field defects, and Mini-Cog results. Of the participants, 28 (6.9%) tested positive on the Mini-Cog, suggesting cognitive impairment. The average SC level in the Mini-Cog positive group was significantly lower than in the negative group (269.5 ± 86.4 A.U. vs. 329.2 ± 120.4 A.U., respectively; p = 0.01). Additionally, the visual field mean deviation (MD) in the Mini-Cog positive group was notably worse than that in the negative group (−19.64 ± 9.07 dB vs. −12.46 ± 9.28 dB, respectively; p < 0.0001). The mixed-effects regression analysis revealed a significant association between Mini-Cog positivity and lower SC levels (p = 0.0006), although SC levels did not significantly correlate with MD (p = 0.3). Our findings suggest that cognitive impairment in glaucoma patients is associated with lower SC levels, underscoring the potential benefits of maintaining carotenoid levels to slow cognitive function decline. The protective role of carotenoids in glaucoma merits further investigation. Full article

(This article belongs to the Special Issue Aging and Oxidative Stress in Nervous System)

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37 pages, 809 KiB

Open AccessReview

A Synopsis of Biomarkers in Glioblastoma: Past and Present

by Ligia Gabriela Tataranu, Serban Turliuc, Radu Eugen Rizea, Anica Dricu, Oana Alexandru, Georgiana-Adeline Staicu and Amira Kamel

Curr. Issues Mol. Biol. 2024, 46(7), 6903-6939; https://doi.org/10.3390/cimb46070412 - 3 Jul 2024

Viewed by 410

Abstract

Accounting for 48% of malignant brain tumors in adults, glioblastoma has been of great interest in the last decades, especially in the biomolecular and neurosurgical fields, due to its incurable nature and notable neurological morbidity. The major advancements in neurosurgical technologies have positively [...] Read more.

Accounting for 48% of malignant brain tumors in adults, glioblastoma has been of great interest in the last decades, especially in the biomolecular and neurosurgical fields, due to its incurable nature and notable neurological morbidity. The major advancements in neurosurgical technologies have positively influenced the extent of safe tumoral resection, while the latest progress in the biomolecular field of GBM has uncovered new potential therapeutical targets. Although GBM currently has no curative therapy, recent progress has been made in the management of this disease, both from surgical and molecular perspectives. The main current therapeutic approach is multimodal and consists of neurosurgical intervention, radiotherapy, and chemotherapy, mostly with temozolomide. Although most patients will develop treatment resistance and tumor recurrence after surgical removal, biomolecular advancements regarding GBM have contributed to a better understanding of this pathology and its therapeutic management. Over the past few decades, specific biomarkers have been discovered that have helped predict prognosis and treatment responses and contributed to improvements in survival rates. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics in Brain Disorders)

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18 pages, 6927 KiB

Open AccessArticle

Pereskia sacharosa Griseb. (Cactaceae) Prevents Lipopolysaccharide-Induced Neuroinflammation in Rodents via Down-Regulating TLR4/CD14 Pathway and GABAA γ2 Activity

by María Fernanda Prado-Fernández, Víctor Manuel Magdaleno-Madrigal, Emmanuel Cabañas-García, Samuel Mucio-Ramírez, Salvador Almazán-Alvarado, Eugenio Pérez-Molphe-Balch, Yenny Adriana Gómez-Aguirre and Edith Sánchez-Jaramillo

Curr. Issues Mol. Biol. 2024, 46(7), 6885-6902; https://doi.org/10.3390/cimb46070411 - 3 Jul 2024

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Abstract

Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in [...] Read more.

Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in animal models subjected to acute neuroinflammation induced by bacterial lipopolysaccharide (LPS). Coronal brain sections of C57BL/6JN male mice or Wistar male rats administered with EEPs or F10 before LPS were subjected to in situ hybridization to determine c-fos and CD14 mRNA levels in the hypothalamus or GABA_A γ2 mRNA levels in the hippocampus. Theta oscillations were recorded every 6 h in the hippocampus of Wistar rats. In total, five flavonoids and eight phenolic acids were identified and quantified in P. sacharosa leaves. Either EEPs or F10 crossed the blood–brain barrier (BBB) into the brain and reduced the mRNA expression of c-fos, CD14, and GABA_A γ2. A decrease in theta oscillation was observed in the hippocampus of the LPS group, while the F10 + LPS group overrode the LPS effect on theta activity. We conclude that the bioactive compounds of P. sacharosa reduce the central response to inflammation, allowing the early return of ambulatory activity and well-being of the animal. Full article

(This article belongs to the Special Issue Bioactive Molecules: Structure-Activity Relationship)

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17 pages, 642 KiB

Open AccessReview

Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation

by Federica Armeli, Beatrice Mengoni, Debra L. Laskin and Rita Businaro

Curr. Issues Mol. Biol. 2024, 46(7), 6868-6884; https://doi.org/10.3390/cimb46070410 (registering DOI) - 2 Jul 2024

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Abstract

The onset of neurodegenerative diseases involves a complex interplay of pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disorders, highlighting autophagy as pivotal in disease pathogenesis. Reactive [...] Read more.

The onset of neurodegenerative diseases involves a complex interplay of pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disorders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox signaling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a critical antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading altered cell components. The interaction among p62/SQSTM1, Nrf2, and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for therapeutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, this review explores the potential synergy between the endocannabinoid system and Nrf2 signaling for neuroprotection. Further research is needed to elucidate the involved molecular mechanisms and develop effective therapeutic strategies against neurodegeneration. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics in Brain Disorders)

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15 pages, 645 KiB

Open AccessArticle

Telomere Length in a South African Population Co-Infected with HIV and Helminths

by Engelinah D. Macamo, Zilungile L. Mkhize-Kwitshana, Zamathombeni Duma, Julian Mthombeni and Pragalathan Naidoo

Curr. Issues Mol. Biol. 2024, 46(7), 6853-6867; https://doi.org/10.3390/cimb46070409 (registering DOI) - 2 Jul 2024

Viewed by 278

Abstract

Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting [...] Read more.

Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting the association of HIV and parasite co-infection with telomere length. The study aimed to investigate whether telomere length shortening is accelerated in a South African population co-infected with HIV and helminths compared to participants singly infected with either HIV or helminths. Additionally, telomere length data were compared with participants’ biochemical and full blood count parameters. A total of 200 participants were in groups of uninfected control, HIV single infection, helminth single infection and HIV and helminth co-infection groups. Relative telomere length (RTL) was determined using Real-Time PCR and associated with biochemical and full blood count parameters using multivariate regression analysis models that were adjusted for confounders. The uninfected control group was used as a reference group. The uninfected control group had the highest mean RTL (1.21 ± 0.53) while the HIV-infected (0.96 ± 0.42) and co-infected (0.93 ± 0.41) groups had similar RTLs, and lastly, the helminth-infected group (0.83 ± 0.33) had the lowest RTL (p = 0.0002). When compared to the uninfected control group, a significant association between RTL and biochemical parameters, including blood iron (β = −0.48), ferritin (β = −0.48), transferrin saturation (β = −0.57), transferrin (β = −0.57), phosphate (β = −0.47), vitamin A (β = −0.49) and C-reactive protein (β = −0.52) were noted in the co-infected group (p < 0.05). In addition, a significant association between RTL and full blood count, including (β = −0.47), haematocrit (β = −0.46), mean corpuscular volume (β = −0.47), lymphocytes (β = −0.45), mean corpuscular haemoglobin concentration (β = −0.45), red cell distribution width (β = −0.47), monocytes (β = −0.45), eosinophils (β = −0.45), basophils (β = −0.44) and transferrin saturation (β = −0.57) were also noted in the co-infected group (p < 0.05). Accelerated biological ageing, as indicated by telomere length shortening, is associated with HIV and helminth co-infections. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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Open AccessArticle

Reciprocal Interactions of Human Monocytes and Cancer Cells in Co-Cultures In Vitro

by Roman Paduch, Maria Klatka, Paulina Pieniądz, Iwona Wertel, Anna Pawłowska and Janusz Klatka

Curr. Issues Mol. Biol. 2024, 46(7), 6836-6852; https://doi.org/10.3390/cimb46070408 - 2 Jul 2024

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Abstract

The tumor microenvironment (TME) includes immune and stromal cells and noncellular extracellular matrix (ECM) components. Tumor-associated macrophages (TAMs) are the most important immune cells in TME and are crucial for carcinomas’ progression. The purpose was to analyze direct and indirect interactions in co-culture [...] Read more.

The tumor microenvironment (TME) includes immune and stromal cells and noncellular extracellular matrix (ECM) components. Tumor-associated macrophages (TAMs) are the most important immune cells in TME and are crucial for carcinomas’ progression. The purpose was to analyze direct and indirect interactions in co-culture of tumor cells with monocytes/macrophages and, additionally, to indicate which interactions are more important for cancer development. Cytokines, reactive oxygen species, nitric oxide level, tumor cell cycle and changes in tumor cell morphology after human tumor cells (Hep-2 and RK33 cell lines) with human monocyte/macrophage (THP-1 cell line) interactions were tested. Morphology and cytoskeleton organization of tumor cells did not change after co-culture with macrophages. In co-culture of tumor cells with human monocyte, changes in the percentage of tumor cells in cell cycle phases was observed. No significant changes in reactive oxygen species (ROS) were found in the co-culture as compared to the tumor cell mono-culture. Monocytes produced about three times higher ROS than tumor cells. In co-cultures, a lower nitric oxide (NO_x) level was found as compared to the sum of the production by both mono-cultures. Co-culture conditions limited the production of cytokines (IL-4, IL-10 and IL-13) as compared to the sum of their level in mono-cultures. In conclusion, macrophages influence tumor cell growth and functions. Mutual (direct and paracrine) interactions between tumor cells and macrophages changed cytokine production and tumor cell cycle profile. The data obtained may allow us to initially indicate which kind of interactions may have a greater impact on cancer development processes. Full article

(This article belongs to the Special Issue Tumor Immunology: From Molecular Mechanisms to Treatment)

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16 pages, 672 KiB

Open AccessReview

Muscarinic Receptors and Alzheimer’s Disease: New Perspectives and Mechanisms

by Martina Monaco, Hanna Trebesova and Massimo Grilli

Curr. Issues Mol. Biol. 2024, 46(7), 6820-6835; https://doi.org/10.3390/cimb46070407 - 2 Jul 2024

Viewed by 826

Abstract

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases on a global scale. Historically, this pathology has been linked to cholinergic transmission, and despite the scarcity of effective therapies, numerous alternative processes and targets have been proposed as potential avenues for [...] Read more.

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases on a global scale. Historically, this pathology has been linked to cholinergic transmission, and despite the scarcity of effective therapies, numerous alternative processes and targets have been proposed as potential avenues for comprehending this complex illness. Nevertheless, the fundamental pathophysiological mechanisms underpinning AD remain largely enigmatic, with a growing body of evidence advocating for the significance of muscarinic receptors in modulating the brain’s capacity to adapt and generate new memories. This review summarizes the current state of the art in the field of muscarinic receptors’ involvement in AD. A specific key factor was the relationship between comorbidity and the emergence of new mechanisms. Full article

(This article belongs to the Special Issue Metabolism and Molecular Pathology Related Features in Neurological Diseases)

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15 pages, 1425 KiB

Open AccessArticle

The Promising Effect of Ascorbic Acid and Paracetamol as Anti-Biofilm and Anti-Virulence Agents against Resistant Escherichia coli

by Sara M. Eltabey, Ali H. Ibrahim, Mahmoud M. Zaky, Adel Ehab Ibrahim, Yahya Bin Abdullah Alrashdi, Sami El Deeb and Moustafa M. Saleh

Curr. Issues Mol. Biol. 2024, 46(7), 6805-6819; https://doi.org/10.3390/cimb46070406 - 2 Jul 2024

Viewed by 391

Abstract

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of [...] Read more.

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of sub-inhibitory doses of ascorbic acid and paracetamol on Escherichia coli virulence factors. This study evaluated biofilm formation, protease production, motility behavior, serum resistance, expression of virulence-regulating genes (using RT-PCR), and survival rates in a mouse model. Ascorbic acid significantly reduced biofilm formation, protease production, motility, and serum resistance from 100% in untreated isolates to 22–89%, 10–89%, 2–57%, and 31–35% in treated isolates, respectively. Paracetamol also reduced these factors from 100% in untreated isolates to 16–76%, 1–43%, 16–38%, and 31–35%, respectively. Both drugs significantly down-regulated virulence-regulating genes papC, fimH, ompT_m, stcE, fliC, and kpsMTII. Mice treated with these drugs had a 100% survival rate compared with 60% in the positive control group control inoculated with untreated bacteria. This study highlights the potential of ascorbic acid and paracetamol as anti-virulence agents, suggesting their use as adjunct therapies alongside conventional antimicrobials or as alternative treatments for resistant Escherichia coli infections. Full article

(This article belongs to the Special Issue Molecular Biology in Drug Design and Precision Therapy)

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22 pages, 2141 KiB

Open AccessReview

A Comprehensive View on the Impact of Chlorogenic Acids on Colorectal Cancer

by Andreea-Adriana Neamțu, Teodor Andrei Maghiar, Violeta Turcuș, Paula Bianca Maghiar, Anca-Maria Căpraru, Bianca-Andreea Lazar, Cristina-Adriana Dehelean, Ovidiu Laurean Pop, Carmen Neamțu, Bogdan Dan Totolici and Endre Mathe

Curr. Issues Mol. Biol. 2024, 46(7), 6783-6804; https://doi.org/10.3390/cimb46070405 - 2 Jul 2024

Viewed by 307

Abstract

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. [...] Read more.

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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Curr. Issues Mol. Biol., Volume 46, Issue 7 (July 2024) – 59 articles

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