Current Issues in Molecular Biology

14 pages, 303 KiB

Open AccessArticle

Analysis of Genes Related to Invadopodia Formation and CTTN in Oral Squamous Cell Carcinoma—A Systematic Gene Expression Analysis

by Immanuel Desel, Susanne Jung, Nikolai Purcz, Yahya Açil, Christoph Sproll, Johannes Kleinheinz and Sonja Sielker

Curr. Issues Mol. Biol. 2023, 45(8), 6927-6940; https://doi.org/10.3390/cimb45080437 - 18 Aug 2023

Cited by 1 | Viewed by 1500

Abstract

Successful treatment for any type of carcinoma largely depends on understanding the patterns of invasion and migration. For oral squamous cell carcinoma (OSCC), these processes are not entirely understood as of now. Invadopodia and podosomes, called invadosomes, play an important role in cancer [...] Read more.

Successful treatment for any type of carcinoma largely depends on understanding the patterns of invasion and migration. For oral squamous cell carcinoma (OSCC), these processes are not entirely understood as of now. Invadopodia and podosomes, called invadosomes, play an important role in cancer cell invasion and migration. Previous research has established that cortactin (CTTN) is a major inducer of invadosome formation. However, less is known about the expression patterns of CTTN and other genes related to it or invadopodia formation in OSCC during tumor progression in particular. In this study, gene expression patterns of CTTN and various genes (n = 36) associated with invadopodia formation were analyzed to reveal relevant expression patterns and give a comprehensive overview of them. The genes were analyzed from a whole genome dataset of 83 OSCC samples relating to tumor size, grading, lymph node status, and UICC (Union for Internatioanl Cancer Control). The data revealed significant overexpression of 18 genes, most notably CTTN, SRC (SRC proto-onocogene, non-receptor tyrosine kinase), EGFR (epidermal growth factor receptor), SYK (spleen associated tyrosine kinase), WASL (WASP like actin nucleation promotion factor), and ARPC2 (arrestin beta 1) due to their significant correlation with further tumor parameters. This study is one of the first to summarize the expression patterns of CTTN and related genes in a complex group of OSCC samples. Full article

(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)

11 pages, 2602 KiB

Open AccessArticle

Hexavalent Chromium Inhibited Zebrafish Embryo Development by Altering Apoptosis- and Antioxidant-Related Genes

by Khoa Dang Dang, Chi Nguyen Quynh Ho, Huy Duc Van, Son Thanh Dinh, Quynh Thi Truc Nguyen, Tram Thi Thuy Nguyen, Xuyen Thi Ngoc Kien, Tuyet Van Dao, Hung Viet Nong, Minh Thai Nguyen, Chung Chinh Doan, Son Nghia Hoang, Thao Thi Phuong Nguyen and Long Thanh Le

Curr. Issues Mol. Biol. 2023, 45(8), 6916-6926; https://doi.org/10.3390/cimb45080436 - 18 Aug 2023

Cited by 1 | Viewed by 1665

Abstract

This study aimed to assess the effects of hexavalent chromium on zebrafish (Danio rerio) embryo development. The zebrafish embryos were treated with solutions containing chromium at different concentrations (0.1, 1, 3.125, 6.25, 12.5, 50, and 100 µg/mL). The development of zebrafish [...] Read more.

This study aimed to assess the effects of hexavalent chromium on zebrafish (Danio rerio) embryo development. The zebrafish embryos were treated with solutions containing chromium at different concentrations (0.1, 1, 3.125, 6.25, 12.5, 50, and 100 µg/mL). The development of zebrafish embryos was estimated by the determination of survival rate, heart rate, and the measurement of larvae body length. Real time RT-PCR and Western blot were performed to assess the expression of apoptosis- and antioxidant-related genes. The results showed that the reduced survival rate of zebrafish embryos and larvae was associated with an increase in chromium concentration. The exposure of higher concentrations resulted in a decrease in body length of zebrafish larvae. In addition, a marked increase in heart rate was observed in the zebrafish larvae under chromium treatment, especially at high concentrations. The real-time RT-PCR analysis showed that the transcript expressions for cell-cycle-related genes (cdk4 and cdk6) and antioxidant-related genes (sod1 and sod2) were downregulated in the zebrafish embryos treated with chromium. Western blot analysis revealed the upregulation of Caspase 3 and Bax, while a downregulation was observed in Bcl2. These results indicated that hexavalent chromium induced changes in zebrafish embryo development by altering apoptosis- and antioxidant-related genes. Full article

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

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13 pages, 757 KiB

Open AccessArticle

Development and Evaluation of a New qPCR Assay for the Detection of Mycoplasma in Cell Cultures

by José A. Carrillo-Ávila, Amanda de la Fuente, Rocío Aguilar-Quesada, Gertrudis Ligero, Juan Manuel del Río-Ortiz and Purificación Catalina

Curr. Issues Mol. Biol. 2023, 45(8), 6903-6915; https://doi.org/10.3390/cimb45080435 - 18 Aug 2023

Cited by 2 | Viewed by 3088

Abstract

In recent years, cell culture has become an important tool not only in research laboratories, but also in diagnostic and biotechnological development laboratories. Mycoplasma contamination is present in up to 35% of cell cultures used in research and in cell therapies. This fact [...] Read more.

In recent years, cell culture has become an important tool not only in research laboratories, but also in diagnostic and biotechnological development laboratories. Mycoplasma contamination is present in up to 35% of cell cultures used in research and in cell therapies. This fact represents a significant problem since such contamination can cause disastrous effects on eukaryotic cells by altering their cellular parameters, which, in turn, can lead to unreliable experimental results. For this reason, it is mandatory to carry out continuous testing for the presence of Mycoplasma in cell culture and the development of appropriate methodologies for this purpose. An ideal detection methodology should be fast, sensitive, and reliable. In this study, we propose an alternative detection method based on real-time PCR in conjunction with a novel combination of primers and probes that have been improved to increase their efficiency. The new PCR method demonstrates 100% sensitivity and specificity results in the detection of common Mycoplasma species that contaminate cell cultures. Whilst 11 of 45 tested supernatants were positive for Mycoplasma (24.4%) using the new PCR method (corresponding to 5 of the 14 lines tested (35.71%)), only 10 of 45 supernatants showed positive results with the commercial Venor^®GeM qEP and Plasmotest^® kit. In addition, the new PCR method exhibits a high capacity to detect less-frequent Mycoplasma species, such as those related to the M. mycoides cluster. The use of an alternative Mycoplasma-detection method in cell culture labs can guarantee the detection of Mycoplasma contamination, especially in cases when dubious results are recorded. Full article

(This article belongs to the Special Issue Next-Generation Sequencing (NGS) Technique and Personalized Medicine)

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23 pages, 4133 KiB

Open AccessReview

Moringa oleifera: A Review on the Antiproliferative Potential in Breast Cancer Cells

by Malebogo M. Moremane, Beynon Abrahams and Charlette Tiloke

Curr. Issues Mol. Biol. 2023, 45(8), 6880-6902; https://doi.org/10.3390/cimb45080434 - 18 Aug 2023

Cited by 8 | Viewed by 2989

Abstract

The global burden of female breast cancer and associated deaths has become a major concern. Many chemotherapeutic agents, such as doxorubicin, have been shown to have adverse side effects. The development of multi-drug resistance is a common occurrence, contributing to chemotherapeutic failure. The [...] Read more.

The global burden of female breast cancer and associated deaths has become a major concern. Many chemotherapeutic agents, such as doxorubicin, have been shown to have adverse side effects. The development of multi-drug resistance is a common occurrence, contributing to chemotherapeutic failure. The resistance of breast cancer cells to drug treatment leads to a decline in the treatment efficacy and an increase in cancer recurrence. Therefore, action is required to produce alternative drug therapies, such as herbal drugs. Herbal drugs have been proven to be beneficial in treating illnesses, including cancer. This review aims to highlight the antiproliferative potential of Moringa oleifera (MO), a medicinal tree native to India and indigenous to Africa, in breast cancer cells. Although MO is not yet considered a commercial chemopreventive drug, previous studies have indicated that it could become a chemotherapeutic agent. The possible antiproliferative potential of MO aqueous leaf extract has been previously proven through its antioxidant potential as well as its ability to induce apoptosis. This review will provide an increased understanding of the effect that MO aqueous leaf extract could potentially have against breast cancer. Full article

(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)

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29 pages, 9460 KiB

Open AccessReview

Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

by Polina N. Kamzeeva, Andrey V. Aralov, Vera A. Alferova and Vladimir A. Korshun

Curr. Issues Mol. Biol. 2023, 45(8), 6851-6879; https://doi.org/10.3390/cimb45080433 - 17 Aug 2023

Cited by 8 | Viewed by 3649

Abstract

The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the [...] Read more.

The search for new drugs has been greatly accelerated by the emergence of new viruses and drug-resistant strains of known pathogens. Nucleoside analogues (NAs) are a prospective class of antivirals due to known safety profiles, which are important for rapid repurposing in the fight against emerging pathogens. Recent improvements in research methods have revealed new unexpected details in the mechanisms of action of NAs that can pave the way for new approaches for the further development of effective drugs. This review accounts advanced techniques in viral polymerase targeting, new viral and host enzyme targeting approaches, and prodrug-based strategies for the development of antiviral NAs. Full article

(This article belongs to the Special Issue Advanced Research in Antimicrobial and Antiviral Drugs)

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Graphical abstract

9 pages, 1039 KiB

Open AccessCommunication

HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico

by Denisse Stephania Becerra-Loaiza, Luisa Fernanda Roldan Flores, Luis Antonio Ochoa-Ramírez, Bricia M. Gutiérrez-Zepeda, Alicia Del Toro-Arreola, Ramón Antonio Franco-Topete, Andrés Morán-Mendoza, Antonio Oceguera-Villanueva, Antonio Topete, David Javalera, Antonio Quintero-Ramos and Adrián Daneri-Navarro

Curr. Issues Mol. Biol. 2023, 45(8), 6842-6850; https://doi.org/10.3390/cimb45080432 - 16 Aug 2023

Cited by 1 | Viewed by 1682

Abstract

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3′UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of [...] Read more.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3′UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex–age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16–7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required. Full article

(This article belongs to the Special Issue Advanced Molecular Solutions for Cancer Therapy)

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19 pages, 2355 KiB

Open AccessArticle

Differential Expression of Subsets of Genes Related to HDL Metabolism and Atherogenesis in the Peripheral Blood in Coronary Artery Disease

by Alexander D. Dergunov, Elena V. Nosova, Alexandra V. Rozhkova, Margarita A. Vinogradina, Veronika B. Baserova, Mikhail A. Popov, Svetlana A. Limborska and Liudmila V. Dergunova

Curr. Issues Mol. Biol. 2023, 45(8), 6823-6841; https://doi.org/10.3390/cimb45080431 - 16 Aug 2023

Cited by 2 | Viewed by 1593

Abstract

Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 [...] Read more.

Differential expression of genes (DEGs) in coronary artery disease (CAD) and the association between transcript level and high-density lipoprotein cholesterol (HDL-C) were studied with 76 male patients with CAD and 63 control patients. The transcript level of genes related to HDL metabolism (24 genes) and atherosclerosis-prone (41 genes) in RNA isolated from peripheral blood mononuclear cells was measured by real-time RT-PCR. Twenty-eight DEGs were identified. The expression of cholesterol transporters, ALB, APOA1, and LCAT was down-regulated, while the expression of AMN, APOE, LDLR, LPL, PLTP, PRKACA, and CETP was up-regulated. The systemic inflammation in CAD is evidenced by the up-regulation of IL1B, TLR8, CXCL5, and TNFRSF1A. For the controls, TLR8 and SOAT1 were negative predictors of the HDL-C level. For CAD patients, PRKACG, PRKCQ, and SREBF1 were positive predictors, while PRKACB, LCAT, and S100A8 were negative predictors. For CAD patients, the efficiency of reverse cholesterol transport is 73–79%, and intracellular free cholesterol seems to accumulate at hyperalphalipoproteinemia. Both atheroprotective (via S100A8) and proatherogenic (via SREBF1, LCAT, PRKACG, PRKACB, and PRKCQ) associations of gene expression with HDL-C determine HDL functionality in CAD patients. The selected key genes and involved pathways may represent HDL-specific targets for the diagnosis and treatment of CAD and atherosclerosis. Full article

(This article belongs to the Special Issue A Focus on Molecular Basis in Cardiac Diseases)

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19 pages, 5036 KiB

Open AccessArticle

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

by Fei Cao, Xintong Wang, Qingqing Ye, Fang Yan, Weicheng Lu, Jingdun Xie, Bingtian Bi and Xudong Wang

Curr. Issues Mol. Biol. 2023, 45(8), 6804-6822; https://doi.org/10.3390/cimb45080430 - 16 Aug 2023

Viewed by 1833

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA–miRNA–mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research. Full article

(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)

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14 pages, 6393 KiB

Open AccessArticle

Unveiling Nilaparvata lugens Stål Genes Defining Compatible and Incompatible Interactions with Rice through Transcriptome Analysis and Gene Silencing

by Priyadarshini Rout, Nihal Ravindranath, Dinkar Gaikwad and Satyabrata Nanda

Curr. Issues Mol. Biol. 2023, 45(8), 6790-6803; https://doi.org/10.3390/cimb45080429 - 16 Aug 2023

Cited by 1 | Viewed by 1309

Abstract

The brown planthopper (Nilaparvata lugens Stål, BPH) is a major pest of rice (Oryza sativa L.), causing severe crop loss. Multiple biotypes and emerging populations of BPH pose a bigger challenge for the infestations control. Although several studies have been conducted [...] Read more.

The brown planthopper (Nilaparvata lugens Stål, BPH) is a major pest of rice (Oryza sativa L.), causing severe crop loss. Multiple biotypes and emerging populations of BPH pose a bigger challenge for the infestations control. Although several studies have been conducted to understand the molecular mechanisms of rice–BPH interactions, there are few studies dedicated to the Indian sub-continent BPH biotype (biotype 4). Here, we analyzed the transcriptomic, physiological, and gene-silencing responses of the BPH biotype 4 during the compatible (fed on susceptible Taichung Native 1, TN1 rice) and incompatible (fed on resistant PTB33 rice) rice–BPH interactions. In the incompatible interaction, a significant reduction in the honeydew production and negative weight gain were observed in the BPH. Similarly, the trehalose and glucose contents were found to be significantly high and low, respectively, during the incompatible rice–BPH interaction. The comparative BPH transcriptome analysis identified 1875 differentially expressive genes (DEGs) between the compatible and incompatible interactions from which many were annotated to be involved in vital BPH physiological processes, including cuticle development, sugar metabolism, detoxification, molting, and xenobiotics metabolism. The RNA interference-mediated independent silencing of three selected genes, including NlCP1, NlCYP320a1, and NlTret1, revealed that these genes are important for BPH physiology and survival. Moreover, the results of this study provide valuable insights into the rice–BPH interactions involving the BPH biotype 4. Full article

(This article belongs to the Section Molecular Plant Sciences)

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15 pages, 4102 KiB

Open AccessArticle

Mixed Medicinal Mushroom Mycelia Attenuates Alzheimer’s Disease Pathologies In Vitro and In Vivo

by Ji Heun Jeong, Geum-Lan Hong, Young Gil Jeong, Nam Seob Lee, Do Kyung Kim, Jong Yea Park, Mina Park, Hyun Min Kim, Ya El Kim, Yung Choon Yoo and Seung Yun Han

Curr. Issues Mol. Biol. 2023, 45(8), 6775-6789; https://doi.org/10.3390/cimb45080428 - 15 Aug 2023

Cited by 2 | Viewed by 1901

Abstract

Alzheimer’s disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed [...] Read more.

Alzheimer’s disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM)—Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus—cultivated on a barley medium was assessed for its anti-AD effects. Neuron-like PC12 cells, which were subjected to Zn²⁺, an Aβ aggregator, were employed as an in vitro AD model. The cells pretreated with or without MMMM were assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. Then, 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and incrementation in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaque accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation and neuroinflammation, by impeding Aβ-induced neurotoxicity. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics in Neurodegenerative Diseases)

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32 pages, 9561 KiB

Open AccessArticle

Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells

by Gregory Ian Robinson, Dongping Li, Bo Wang, Yeva Zahoruiko, Marta Gerasymchuk, Darryl Hudson, Olga Kovalchuk and Igor Kovalchuk

Curr. Issues Mol. Biol. 2023, 45(8), 6743-6774; https://doi.org/10.3390/cimb45080427 - 15 Aug 2023

Cited by 12 | Viewed by 4477

Abstract

Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanserin (Ket), along with [...] Read more.

Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanserin (Ket), along with transient receptor potential (TRP) channel ligands like capsaicin (Cap), curcumin (Cur), and eugenol (Eug), show promise as anti-inflammatory agents. In this study, we investigated the cytotoxic and anti-inflammatory effects of Psi, 4-AcO-DMT, Ket, Cap, Cur, and Eug on human small intestinal epithelial cells (HSEIC). HSEIC were exposed to tumor necrosis factor (TNF)-α and interferon (IFN)-γ for 24 h to induce an inflammatory response, followed by treatment with each compound at varying doses (0–800 μM) for 24 to 96 h. The cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and protein expression by Western blot (WB) analysis. As single treatments, Psi (40 μM), Cur (0.5 μM), and Eug (50 μM) significantly reduced COX-2 levels without cytotoxic effects. When combined, Psi (40 μM) and Cur (0.5 μM) exhibited synergy, resulting in a substantial decrease in COX-2 protein levels (−28× fold change), although the reduction in IL-6 was less pronounced (−1.6× fold change). Psi (20 μM) and Eug (25 μM) demonstrated the most favorable outcomes, with significant decreases in COX-2 (−19× fold change) and IL-6 (−10× fold change) protein levels. Moreover, the combination of Psi and Eug did not induce cytotoxic effects in vitro at any tested doses. This study is the first to explore the anti-inflammatory potential of psilocybin and 4-AcO-DMT in the intestines while highlighting the potential for synergy between the 5-HT2A and TRP channel ligands, specifically Psi and Eug, in alleviating the TNF-α/IFN-γ-induced inflammatory response in HSEIC. Further investigations should evaluate if the Psi and Eug combination has the therapeutic potential to treat IBD in vivo. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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15 pages, 2839 KiB

Open AccessReview

Relevant Properties and Potential Applications of Sericin in Bone Regeneration

by Jwa-Young Kim, Seong-Gon Kim and Umberto Garagiola

Curr. Issues Mol. Biol. 2023, 45(8), 6728-6742; https://doi.org/10.3390/cimb45080426 - 15 Aug 2023

Cited by 4 | Viewed by 2199

Abstract

The potential of sericin, a protein derived from silkworms, is explored in bone graft applications. Sericin’s biocompatibility, hydrophilic nature, and cost-effectiveness make it a promising candidate for enhancing traditional graft materials. Its antioxidant, anti-inflammatory, and UV-resistant properties contribute to a healthier bone-healing environment, [...] Read more.

The potential of sericin, a protein derived from silkworms, is explored in bone graft applications. Sericin’s biocompatibility, hydrophilic nature, and cost-effectiveness make it a promising candidate for enhancing traditional graft materials. Its antioxidant, anti-inflammatory, and UV-resistant properties contribute to a healthier bone-healing environment, and its incorporation into 3D-printed grafts could lead to personalized medical solutions. However, despite these promising attributes, there are still gaps in our understanding. The precise mechanism through which sericin influences bone cell growth and healing is not fully understood, and more comprehensive clinical trials are needed to confirm its long-term biocompatibility in humans. Furthermore, the best methods for incorporating sericin into existing graft materials are still under investigation, and potential allergic reactions or immune responses to sericin need further study. Full article

(This article belongs to the Special Issue Recent Advances in Musculoskeletal Regenerative Medicine)

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11 pages, 1957 KiB

Open AccessArticle

Length-Dependent Translation Efficiency of ER-Destined Proteins

by Hana Sahinbegovic, Alexander Vdovin, Renata Snaurova, Michal Durech, Jakub Nezval, Jiri Sobotka, Roman Hajek, Tomas Jelinek and Michal Simicek

Curr. Issues Mol. Biol. 2023, 45(8), 6717-6727; https://doi.org/10.3390/cimb45080425 - 14 Aug 2023

Viewed by 2495

Abstract

Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with [...] Read more.

Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with an N-terminal signal sequences that direct the translation apparatus toward a specific organelle. Here, we focus on the mechanisms governing the translation of mRNAs, which encode proteins with an endoplasmic reticulum (ER) signal in human cells. The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA–ribosome complex reaches the ER membrane. The commonly accepted model suggests that mRNA that encodes a protein that contains an ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with the ER. In contrast to the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to low ribosome occupancy, the short mRNAs continue the cycle, always facing a translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings. Full article

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

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13 pages, 2595 KiB

Open AccessArticle

Priestia megaterium Metabolism: Isolation, Identification of Naringenin Analogues and Genes Elevated Associated with Nanoparticle Intervention

by Nada S. Al-Theyab, Hatem A. Abuelizz, Gadah A. Al-Hamoud, Ahmad Aldossary and Mingtao Liang

Curr. Issues Mol. Biol. 2023, 45(8), 6704-6716; https://doi.org/10.3390/cimb45080424 - 14 Aug 2023

Viewed by 2111

Abstract

The impact of gold nanoparticles (AuNPs) on the biosynthetic manipulation of Priestia megaterium metabolism where an existing gene cluster is enhanced to produce and enrich bioactive secondary metabolites has been studied previously. In this research, we aimed to isolate and elucidate the structure [...] Read more.

The impact of gold nanoparticles (AuNPs) on the biosynthetic manipulation of Priestia megaterium metabolism where an existing gene cluster is enhanced to produce and enrich bioactive secondary metabolites has been studied previously. In this research, we aimed to isolate and elucidate the structure of metabolites of compounds 1 and 2 which have been analyzed previously in P. megaterium crude extract. This was achieved through a PREP-ODS C18 column with an HPLC-UV/visible detector. Then, the compounds were subjected to nuclear magnetic resonance (NMR), electrospray ionization mass spectrometry (ESI-MS), and Fourier-transform infrared spectroscopy (FT-IR) techniques. Furthermore, bioinformatics and transcriptome analysis were used to examine the gene expression for which the secondary metabolites produced in the presence of AuNPs showed significant enhancement in transcriptomic responses. The metabolites of compounds 1 and 2 were identified as daidzein and genistein, respectively. The real-time polymerase chain reaction (RT-PCR) technique was used to assess the expression of three genes (csoR, CHS, and yjiB) from a panel of selected genes known to be involved in the biosynthesis of the identified secondary metabolites. The expression levels of two genes (csoR and yijB) increased in response to AuNP intervention, whereas CHS was unaffected. Full article

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

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3 pages, 184 KiB

Open AccessEditorial

Editorial for the Special Issue “Advanced Research in Plant Metabolomics”

by Chiara Roberta Girelli

Curr. Issues Mol. Biol. 2023, 45(8), 6701-6703; https://doi.org/10.3390/cimb45080423 - 14 Aug 2023

Viewed by 1193

Abstract

The study of plant metabolome and the role of cellular pathway end products has gained increased attention [...] Full article

(This article belongs to the Special Issue Advanced Research in Plant Metabolomics)

19 pages, 1427 KiB

Open AccessReview

Circular RNAs Variously Participate in Coronary Atherogenesis

by Liudmila V. Dergunova, Margarita A. Vinogradina, Ivan B. Filippenkov, Svetlana A. Limborska and Alexander D. Dergunov

Curr. Issues Mol. Biol. 2023, 45(8), 6682-6700; https://doi.org/10.3390/cimb45080422 - 13 Aug 2023

Cited by 6 | Viewed by 1823

Abstract

Over the past decade, numerous studies have shown that circular RNAs (circRNAs) play a significant role in coronary artery atherogenesis and other cardiovascular diseases. They belong to the class of non-coding RNAs and arise as a result of non-canonical splicing of premature RNA, [...] Read more.

Over the past decade, numerous studies have shown that circular RNAs (circRNAs) play a significant role in coronary artery atherogenesis and other cardiovascular diseases. They belong to the class of non-coding RNAs and arise as a result of non-canonical splicing of premature RNA, which results in the formation of closed single-stranded circRNA molecules that lack 5′-end caps and 3′-end poly(A) tails. circRNAs have broad post-transcriptional regulatory activity. Acting as a sponge for miRNAs, circRNAs compete with mRNAs for binding to miRNAs, acting as competing endogenous RNAs. Numerous circRNAs are involved in the circRNA–miRNA–mRNA regulatory axes associated with the pathogenesis of cardiomyopathy, chronic heart failure, hypertension, atherosclerosis, and coronary artery disease. Recent studies have shown that сirc_0001445, circ_0000345, circ_0093887, сircSmoc1-2, and circ_0003423 are involved in the pathogenesis of coronary artery disease (CAD) with an atheroprotective effect, while circ_0002984, circ_0029589, circ_0124644, circ_0091822, and circ_0050486 possess a proatherogenic effect. With their high resistance to endonucleases, circRNAs are promising diagnostic biomarkers and therapeutic targets. This review aims to provide updated information on the involvement of atherogenesis-related circRNAs in the pathogenesis of CAD. We also discuss the main modern approaches to detecting and studying circRNA–miRNA–mRNA interactions, as well as the prospects for using circRNAs as biomarkers and therapeutic targets for the treatment of cardiovascular diseases. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning, 2nd Volume)

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15 pages, 2210 KiB

Open AccessArticle

Increase in Double Negative B Lymphocytes in Patients with Systemic Lupus Erythematosus in Remission and Their Correlation with Early Differentiated T Lymphocyte Subpopulations

by Eleni Moysidou, Georgios Lioulios, Michalis Christodoulou, Aliki Xochelli, Stamatia Stai, Myrto Iosifidou, Artemis Iosifidou, Sophia Briza, Dimitria Ioanna Briza, Asimina Fylaktou and Maria Stangou

Curr. Issues Mol. Biol. 2023, 45(8), 6667-6681; https://doi.org/10.3390/cimb45080421 - 13 Aug 2023

Cited by 3 | Viewed by 1640

Abstract

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern [...] Read more.

B and T lymphocytes demonstrate important alterations in patients with systemic lupus erythematous (SLE), with a significant upregulation of double negative (DN) B cells. The aim of this study was to evaluate the correlation of T cell immunity changes with the distinct B-cell-pattern SLE. In the present study, flow cytometry was performed in 30 patients in remission of SLE and 31 healthy controls to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations based on the presence of CD45RA, CCR7, CD31, CD28, and CD57, defined as naive, memory, and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased compared to HC (12.9 (2.3–74.2) vs. 8 (1.7–35), p = 0.04). The distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had a significant positive correlation with most of the early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, and CD8CD28+CD57+. Multiple regression analysis revealed CD4CD31+, CD8CD45RA-CD57-, and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, with adjusted R² = 0.534 and p < 0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation. Full article

(This article belongs to the Special Issue Molecular Research in Chronic Dermatoses)

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16 pages, 1450 KiB

Open AccessReview

Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications

by Alfredo Caturano, Margherita D’Angelo, Andrea Mormone, Vincenzo Russo, Maria Pina Mollica, Teresa Salvatore, Raffaele Galiero, Luca Rinaldi, Erica Vetrano, Raffaele Marfella, Marcellino Monda, Antonio Giordano and Ferdinando Carlo Sasso

Curr. Issues Mol. Biol. 2023, 45(8), 6651-6666; https://doi.org/10.3390/cimb45080420 - 12 Aug 2023

Cited by 107 | Viewed by 6716

Abstract

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body’s antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial [...] Read more.

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body’s antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes. Full article

(This article belongs to the Topic Oxidative Stress and Mitochondrial Dysfunction in Metabolic and Inflammatory Diseases)

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17 pages, 2098 KiB

Open AccessArticle

Wheat Water-Soluble Carbohydrate Remobilisation under Water Deficit by 1-FEH w3

by Nusrat Khan, Jingjuan Zhang, Shahidul Islam, Rudi Appels and Bernard Dell

Curr. Issues Mol. Biol. 2023, 45(8), 6634-6650; https://doi.org/10.3390/cimb45080419 - 11 Aug 2023

Viewed by 1681

Abstract

Fructan 1-exohydrolase (1-FEH) is one of the major enzymes in water-soluble carbohydrate (WSC) remobilisation for grains in wheat. We investigated the functional role of 1-FEH w1, w2, and w3 isoforms in WSC remobilisation under post-anthesis water deficit using mutation lines derived [...] Read more.

Fructan 1-exohydrolase (1-FEH) is one of the major enzymes in water-soluble carbohydrate (WSC) remobilisation for grains in wheat. We investigated the functional role of 1-FEH w1, w2, and w3 isoforms in WSC remobilisation under post-anthesis water deficit using mutation lines derived from the Australian wheat variety Chara. F1 seeds, developed by backcrossing the 1-FEH w1, w2, and w3 mutation lines with Chara, were genotyped using the Infinium 90K SNP iSelect platform to characterise the mutated region. Putative deletions were identified in FEH mutation lines encompassing the FEH genomic regions. Mapping analysis demonstrated that mutations affected significantly longer regions than the target FEH gene regions. Functional roles of the non-target genes were carried out utilising bioinformatics and confirmed that the non-target genes were unlikely to confound the effects considered to be due to the influence of 1-FEH gene functions. Glasshouse experiments revealed that the 1-FEH w3 mutation line had a slower degradation and remobilisation of fructans than the 1-FEH w2 and w1 mutation lines and Chara, which reduced grain filling and grain yield. Thus, 1-FEH w3 plays a vital role in reducing yield loss under drought. This insight into the distinct role of the 1-FEH isoforms provides new gene targets for water-deficit-tolerant wheat breeding. Full article

(This article belongs to the Special Issue Advanced Research in Wheat Genome and Breeding)

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16 pages, 3823 KiB

Open AccessArticle

Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes BReast CAncer 1 and BReast CAncer 2

by Tara Zuhair Kassem, Marius Wunderle, Lukas Kuhlmann, Matthias Ruebner, Hanna Huebner, Juliane Hoyer, André Reis, Peter A. Fasching, Matthias W. Beckmann, Carolin C. Hack, Rainer Fietkau and Luitpold Distel

Curr. Issues Mol. Biol. 2023, 45(8), 6618-6633; https://doi.org/10.3390/cimb45080418 - 10 Aug 2023

Cited by 1 | Viewed by 1672

Abstract

Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as BRCA1 and BRCA2. By studying the chromosomal radiosensitivity [...] Read more.

Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as BRCA1 and BRCA2. By studying the chromosomal radiosensitivity of BRCA1/2 mutation carriers compared to the general population, we study whether increased chromosomal radiation sensitivity is observed in patients with BRCA1/2 variants. Methods: Three-color-fluorescence in situ hybridization was performed on ex vivo-irradiated peripheral blood lymphocytes from 64 female patients with a heterozygous germline BRCA1 or BRCA2 mutation. Aberrations in chromosomes #1, #2 and #4 were analyzed. Mean breaks per metaphase (B/M) served as the parameter for chromosomal radiosensitivity. The results were compared with chromosomal radiosensitivity in a cohort of generally healthy individuals and patients with rectal cancer or breast cancer. Results: Patients with BRCA1/2 mutations (n = 64; B/M 0.47) overall showed a significantly higher chromosomal radiosensitivity than general healthy individuals (n = 211; B/M 0.41) and patients with rectal cancer (n = 379; B/M 0.44) and breast cancer (n = 147; B/M 0.45) without proven germline mutations. Chromosomal radiosensitivity varied depending on the locus of the BRCA1/2 mutation. Conclusions: BRCA1/2 mutations result in slightly increased chromosomal sensitivity to radiation. A few individual patients have a marked increase in radiation sensitivity. Therefore, these patients are at a higher risk for adverse therapeutic consequences. Full article

(This article belongs to the Special Issue Advanced Research of Ionizing Radiation in Cancers)

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13 pages, 2932 KiB

Open AccessArticle

Diagnosis of a Rabbit Hemorrhagic Disease Virus 2 (RHDV2) and the Humoral Immune Protection Effect of VP60 Vaccine

by Zhaoming Li, Kaimin Song, Yongzhen Du, Zhuanglong Zhang, Rupeng Fan, Pimiao Zheng and Jianzhu Liu

Curr. Issues Mol. Biol. 2023, 45(8), 6605-6617; https://doi.org/10.3390/cimb45080417 - 8 Aug 2023

Cited by 1 | Viewed by 2432

Abstract

Rabbit hemorrhagic disease (RHD) is known as rabbit plague and hemorrhagic pneumonia. It is an acute, septic, and highly fatal infectious disease caused by the Lagovirus rabbit hemorrhagic disease virus (RHDV) in the family Caliciviridae that infects wild and domestic rabbits and hares [...] Read more.

Rabbit hemorrhagic disease (RHD) is known as rabbit plague and hemorrhagic pneumonia. It is an acute, septic, and highly fatal infectious disease caused by the Lagovirus rabbit hemorrhagic disease virus (RHDV) in the family Caliciviridae that infects wild and domestic rabbits and hares (lagomorphs). At present, RHDV2 has caused huge economic losses to the commercial rabbit trade and led to a decline in the number of wild lagomorphs worldwide. We performed a necropsy and pathological observations on five dead rabbits on a rabbit farm in Tai’an, China. The results were highly similar to the clinical and pathological changes of typical RHD. RHDV2 strain was isolated and identified by RT-PCR, and partial gene sequencing and genetic evolution analysis were carried out. There were significant differences in genetic characteristics and antigenicity between RHDV2 and classical RHDV strain, and the vaccine prepared with the RHDV strain cannot effectively prevent rabbit infection with RHDV2. Therefore, we evaluated the protective efficacy of a novel rabbit hemorrhagic virus baculovirus vector inactivated vaccine (VP60) in clinical application by animal regression experiment. The result showed that VP60 could effectively induce humoral immunity in rabbits. The vaccine itself had no significant effect on the health status of rabbits. This study suggested that the clinical application of VP60 may provide new ideas for preventing the spread of RHD2. Full article

(This article belongs to the Special Issue Latest Advances in Molecular and Cellular Virology)

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12 pages, 2697 KiB

Open AccessArticle

Aging Aggravates Periodontal Inflammatory Responses and Alveolar Bone Resorption by Porphyromonas gingivalis Infection

by Yuri Song and Jin Chung

Curr. Issues Mol. Biol. 2023, 45(8), 6593-6604; https://doi.org/10.3390/cimb45080416 - 8 Aug 2023

Cited by 3 | Viewed by 1908

Abstract

Periodontitis is a chronic inflammatory disease driven by periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis), and its prevalence increases with age. However, little is known about the effect of immunosenescence on inflammatory response to P. gingivalis infection. In the present study, 16S rDNA [...] Read more.

Periodontitis is a chronic inflammatory disease driven by periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis), and its prevalence increases with age. However, little is known about the effect of immunosenescence on inflammatory response to P. gingivalis infection. In the present study, 16S rDNA sequencing analysis showed the relative abundance of P. gingivalis was significantly higher in periodontitis patients than healthy group, but there was no difference between the young (20 to 40 years old) and old (65 to 86 years old) periodontitis groups. Furthermore, the cytotoxic effect of P. gingivalis was greater on old THP-1 macrophages and on bone mar-row-derived cells (BMDMs) from old mice, and levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-12 were higher in old than in young THP-1 macrophages. Furthermore, the activations of inflammasome components for IL-1β production by P. gingivalis infection were greater in old THP-1 macrophages. Finally, bone loss was significantly greater in P. gingivalis-infected aged mice than in young mice. These findings indicate that aging aggravates P. gingivalis-induced inflammatory cytokine secretion and inflammasome activation. The study enhances understanding of the relationship between periodontal immunosenescence and inflammatory response in the elderly. Full article

(This article belongs to the Special Issue Complex Molecular Mechanism of Monogenic Diseases 2.0)

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10 pages, 2986 KiB

Open AccessCommunication

The Effects of Sargassum horneri Extract and Fucoidan on Tear Hyposecretion and Ocular Surface Injury in Rats with Dry Eye Diseases

by Su-Bin Park, Woo Kwon Jung, Hwa Young Yu and Junghyun Kim

Curr. Issues Mol. Biol. 2023, 45(8), 6583-6592; https://doi.org/10.3390/cimb45080415 - 8 Aug 2023

Cited by 3 | Viewed by 1682

Abstract

Hyperosmotic stress caused by tear hyposection is a leading cause of dry eye disease. We investigated the prevention of dry eye disease in corneal epithelial cells and in rats that were induced to develop dry eye disease via unilateral excision of their exorbital [...] Read more.

Hyperosmotic stress caused by tear hyposection is a leading cause of dry eye disease. We investigated the prevention of dry eye disease in corneal epithelial cells and in rats that were induced to develop dry eye disease via unilateral excision of their exorbital lacrimal gland using Sargassum horneri extract (AB_SH) and its bioactive component fucoidan. Oral administration of AB_SH (250 mg/kg and 500 mg/kg) and fucoidan (100 mg/kg) was conducted for 7 days. In order to measure tear secretion, phenol red thread tear tests were performed along with corneal irregularity measurements. The apoptotic injury in the cornea and the lacrimal gland was evaluated using TUNEL staining. AB_SH and fucoidan were shown to suppress apoptosis and the expression of apoptosis-related proteins in human corneal epithelial cells under hyperosmotic conditions. Oral administration of AB_SH and fucoidan attenuated tear hyposecretion and corneal irregularity in the lacrimal gland-excised rats. In addition, AB_SH and fucoidan also reduced apoptosis in the cornea and lacrimal gland. This study suggests that S. horneri extract and fucoidan can effectively ameliorate dry eye disease by suppressing the apoptosis of ocular tissues. Full article

(This article belongs to the Special Issue The Role of Bioactives in Inflammation)

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19 pages, 6264 KiB

Open AccessArticle

Mechanism of Taxanes in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking

by Yajing Zhang, Zirui Zhao, Wenlong Li, Yuanhu Tang and Shujie Wang

Curr. Issues Mol. Biol. 2023, 45(8), 6564-6582; https://doi.org/10.3390/cimb45080414 - 7 Aug 2023

Cited by 1 | Viewed by 2278

Abstract

Taxanes are natural compounds for the treatment of lung cancer, but the molecular mechanism behind the effects is unclear. In the present study, through network pharmacology and molecular docking, the mechanism of the target and pathway of taxanes in the treatment of lung [...] Read more.

Taxanes are natural compounds for the treatment of lung cancer, but the molecular mechanism behind the effects is unclear. In the present study, through network pharmacology and molecular docking, the mechanism of the target and pathway of taxanes in the treatment of lung cancer was studied. The taxanes targets were determined by PubChem database, and an effective compounds-targets network was constructed. The GeneCards database was used to determine the disease targets of lung cancer, and the intersection of compound targets and disease targets was obtained. The Protein–Protein Interaction (PPI) network of the intersection targets was analyzed, and the PPI network was constructed by Cytoscape 3.6.0 software. The hub targets were screened according to the degree value, and the binding activity between taxanes and hub targets was verified by molecular docking. The results showed that eight taxane-active compounds and 444 corresponding targets were screened out, and 131 intersection targets were obtained after mapping with lung cancer disease targets. The hub targets obtained by PPI analysis were TP53, EGFR, and AKT1. Gene Ontology (GO) biological function enrichment analysis obtained 1795 biological process (BP) terms, 101 cellular component (CC) terms, and 164 molecular function (MF) terms. There were 179 signaling pathways obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Twenty signaling pathways were screened out, mainly pathways in cancer, proteoglycans in cancer pathway, microRNAs in cancer pathway, and so on. Molecular docking shows that the binding energies of eight taxanes with TP53, EGFR, and AKT1 targets were less than −8.8 kcal/mol, taxanes acts on TP53, EGFR, and AKT1 targets through pathways in cancer, proteoglycans in cancer pathway and microRNAs in cancer pathway, and plays a role in treating lung cancer in biological functions such as protein binding, enzyme binding, and identical protein binding. Full article

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

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14 pages, 934 KiB

Open AccessReview

Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease

by Nava Yugavathy, Bashar Mudhaffar Abdullah, Soo Kun Lim, Abdul Halim Bin Abdul Gafor, Muh Geot Wong, Sunita Bavanandan, Hin Seng Wong and Hasniza Zaman Huri

Curr. Issues Mol. Biol. 2023, 45(8), 6550-6563; https://doi.org/10.3390/cimb45080413 - 7 Aug 2023

Viewed by 2963

Abstract

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) [...] Read more.

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin–iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-β gene (IL-β), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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12 pages, 2753 KiB

Open AccessArticle

Impact of Genomic Deletion RD16 on the Expression of the Mycobacterium bovis BCG Moreau VapBC47 Toxin-Antitoxin System

by Talita Duarte Pagani, Paloma Rezende Corrêa, Cristiane Lima, Leonardo Henrique Ferreira Gomes, Marcos Gustavo Araujo Schwarz, Teca Calcagno Galvão, Wim Maurits Degrave, Napoleão Fonseca Valadares and Leila Mendonça-Lima

Curr. Issues Mol. Biol. 2023, 45(8), 6538-6549; https://doi.org/10.3390/cimb45080412 - 7 Aug 2023

Viewed by 1481

Abstract

Mycobacterium bovis BCG is the only vaccine against tuberculosis. The variable forms of cultivation throughout the years, before seed-lots were developed, allowed in vitro evolution of the original strain, generating a family of vaccines with different phenotypic and genotypic characteristics. Molecular studies revealed [...] Read more.

Mycobacterium bovis BCG is the only vaccine against tuberculosis. The variable forms of cultivation throughout the years, before seed-lots were developed, allowed in vitro evolution of the original strain, generating a family of vaccines with different phenotypic and genotypic characteristics. Molecular studies revealed regions of difference (RDs) in the genomes of the various BCG strains. This work aims to characterize the gene pair rv3407-rv3408 (vapB47-vapC47), coding for a toxin–antitoxin system of the VapBC family, and to evaluate possible transcriptional effects due to the adjacent BCG Moreau-specific genomic deletion RD16. We show that these genes are co-transcribed in BCG strains Moreau and Pasteur, and that the inactivation of an upstream transcriptional repressor (Rv3405c) due to RD16 has a polar effect, leading to increased vapBC47 expression. Furthermore, we detect VapB47 DNA binding in vitro, dependent on a 5′ vapB47 sequence that contributes to a palindrome, spanning the promoter and coding region. Our data shed light on the regulation of VapBC systems and on the impact of the BCG Moreau RD16 deletion in the expression of adjacent genes, contributing to a better understanding of BCG Moreau physiology. Full article

(This article belongs to the Special Issue Molecular Research in Vaccinology and Vaccine Development)

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12 pages, 1277 KiB

Open AccessArticle

An mRNA Profiling Study of Vaginal Swabs from Pre- and Postmenopausal Women

by Elena Chierto, Federica Alessandrini, Carla Bini, Eugenia Carnevali, Matteo Fabbri, Paolo Fattorini, Pierangela Grignani, Francesca Scarnicci, Pamela Tozzo, Andrea Verzeletti, Susi Pelotti, Loredana Buscemi and Carlo Robino

Curr. Issues Mol. Biol. 2023, 45(8), 6526-6537; https://doi.org/10.3390/cimb45080411 - 7 Aug 2023

Cited by 2 | Viewed by 1505

Abstract

Body fluid identification by means of mRNA profiling provides valuable supplementary information in forensic investigations. In particular, the detection of vaginal mucosa mRNA markers is highly relevant in sexual assault cases. Although the vagina undergoes characteristic age-related physiological changes over a lifetime, few [...] Read more.

Body fluid identification by means of mRNA profiling provides valuable supplementary information in forensic investigations. In particular, the detection of vaginal mucosa mRNA markers is highly relevant in sexual assault cases. Although the vagina undergoes characteristic age-related physiological changes over a lifetime, few studies have evaluated the efficacy of vaginal mRNA markers in women of different ages. In this multicentric study, a 19-plex mRNA profiling assay including vaginal-specific markers (CYP2B7P1, MUC4, MYOZ1) was tested in a collection of 6–20-month-old vaginal swabs obtained from pre- (n = 84) and postmenopausal (n = 55) female volunteer donors. Overall, participating laboratories were able to correctly identify ~85% of samples as vaginal mucosa by mRNA profiling. The assay’s success rate did not differ between the two age groups and was not affected by the time interval between swab collection and RNA analysis. MYOZ1 resulted a less sensitive vaginal marker compared to MUC4 and CYP2B7P1. A significant relative increase in the contribution to the total amplification signal was observed for MUC4, compared to CYP2B7P1 and MYOZ1, in postmenopausal women. Observation of other body fluids and tissues different from vaginal mucosa was also evaluated in connection to information on previous sexual activity and menstrual cycle phase at the time of sampling. Full article

(This article belongs to the Special Issue Studying the Function of RNAs Using Omics Approaches)

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23 pages, 2616 KiB

Open AccessArticle

Different RONS Generation in MTC-SK and NSCL Cells Lead to Varying Antitumoral Effects of Alpha-Ketoglutarate + 5-HMF

by Joachim Greilberger, Katharina Erlbacher, Philipp Stiegler, Reinhold Wintersteiger and Ralf Herwig

Curr. Issues Mol. Biol. 2023, 45(8), 6503-6525; https://doi.org/10.3390/cimb45080410 - 7 Aug 2023

Cited by 3 | Viewed by 1888

Abstract

Background: Carbonylated proteins (CPs) serve as specific indicators of increased reactive oxygen and nitrogen species (RONS) production in cancer cells, attributed to the dysregulated mitochondrial energy metabolism known as the Warburg effect. The aim of this study was to investigate the potential of [...] Read more.

Background: Carbonylated proteins (CPs) serve as specific indicators of increased reactive oxygen and nitrogen species (RONS) production in cancer cells, attributed to the dysregulated mitochondrial energy metabolism known as the Warburg effect. The aim of this study was to investigate the potential of alpha-ketoglutarate (aKG), 5-hydroxymethylfurfural (5-HMF), and their combination as mitochondrial-targeting antioxidants in MTC-SK or NCI-H23 cancer cells. Methods: MTC-SK and NCI-H23 cells were cultured in the absence or presence of varying concentrations (0–500 µg/mL) of aKG, 5-HMF, and the combined aKG + 5-HMF solutions. After 0, 24, 48, and 72 h, mitochondrial activity, cancer cell membrane CP levels, cell growth, and caspase-3 activity were assessed in aliquots of MTC-SK and NCI-H23 cells. Results: The mitochondrial activity of MTC-SK cells exhibited a concentration- and time-dependent reduction upon treatment with aKG, 5-HMF, or the combined aKG + 5-HMF. The half-maximal inhibitory concentration (IC50%) for mitochondrial activity was achieved at 500 µg/mL aKG, 200 µg/mL 5-HMF, and 200 µg/mL aKG + 66.7 µg/mL 5-HMF after 72 h. In contrast, NCI-H23 cells showed a minimal reduction (10%) in mitochondrial activity even at the highest combined concentration of aKG + 5-HMF. The CP levels in MTC-SK cells were measured at 8.7 nmol/mg protein, while NCI-H23 cells exhibited CP levels of 1.4 nmol/mg protein. The combination of aKG + 5-HMF led to a decrease in CP levels specifically in MTC-SK cells. The correlation between mitochondrial activity and CP levels in the presence of different concentrations of combined aKG + 5-HMF in MTC-SK cells demonstrated a linear and concentration-dependent decline in CP levels and mitochondrial activity. Conversely, the effect was less pronounced in NCI-H23 cells. Cell growth of MTC-CK cells was reduced to 60% after 48 h and maintained at 50% after 72 h incubation when treated with 500 µg/mL aKG (IC50%). Addition of 500 µg/mL 5-HMF inhibited cell growth completely regardless of the incubation time. The IC50% for 5-HMF on MTC-CK cell growth was calculated at 375 µg/mL after 24 h incubation and 200 µg/mL 5-HMF after 72 h. MTC-SK cells treated with 500 µg/mL aKG + 167 µg/mL 5-HMF showed no cell growth. The calculated IC50% for the combined substances was 250 µg/mL aKG + 83.3 µg/mL 5-HMF (48 h incubation) and 200 µg/mL aKG + 66.7 µg/mL 5-HMF (72 h incubation). None of the tested concentrations of aKG, 5-HMF, or the combined solution had any effect on NCI-H23 cell growth at any incubation time. Caspase-3 activity increased to 21% in MTC-CK cells in the presence of 500 µg/mL aKG, while an increase to 59.6% was observed using 500 µg/mL 5-HMF. The combination of 500 µg/mL aKG + 167.7 µg/mL 5-HMF resulted in a caspase-3 activity of 55.2%. No caspase-3 activation was observed in NCI-H23 cells when treated with aKG, 5-HMF, or the combined solutions. Conclusion: CPs may serve as potential markers for distinguishing between cancer cells regulated by RONS. The combination of aKG + 5-HMF showed induced cell death in high-RONS-generating cancer cells compared to low-RONS-generating cancer cells. Full article

(This article belongs to the Special Issue Mitochondrial Function and Dysfunction)

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18 pages, 5208 KiB

Open AccessArticle

Multidrug Resistance Profiles and Resistance Mechanisms to β-Lactams and Fluoroquinolones in Bacterial Isolates from Hospital Wastewater in Bangladesh

by Rasel Khan Manik, Zimam Mahmud, Israt Dilruba Mishu, Md Sourav Hossen, Zakir Hossain Howlader and A. H. M. Nurun Nabi

Curr. Issues Mol. Biol. 2023, 45(8), 6485-6502; https://doi.org/10.3390/cimb45080409 - 5 Aug 2023

Cited by 5 | Viewed by 1787

Abstract

Multidrug resistance (MDR) is one of the deadliest public health concerns of the 21st century, rendering many powerful antibiotics ineffective. The current study provides important insights into the prevalence and mechanisms of antibiotic resistance in hospital wastewater isolates. In this study, we determined [...] Read more.

Multidrug resistance (MDR) is one of the deadliest public health concerns of the 21st century, rendering many powerful antibiotics ineffective. The current study provides important insights into the prevalence and mechanisms of antibiotic resistance in hospital wastewater isolates. In this study, we determined the MDR profile of 68 bacterial isolates collected from five different hospitals in Dhaka, Bangladesh. Of them, 48 bacterial isolates were identified as Enterobacteriaceae. Additionally, we investigated the prevalence and distribution of five beta-lactam resistance genes, as well as quinolone resistance mechanisms among the isolates. The results of this study showed that 87% of the wastewater isolates were resistant to at least three different antibiotic classes, as revealed using the disc diffusion method. Resistance to β-lactams was the most common, with 88.24% of the isolates being resistant, closely followed by macrolides (80.88% resistant). Polymyxin was found to be the most effective against wastewater isolates, with 29.41% resistant isolates. The most common β-lactam resistance genes found in wastewater isolates were bla_TEM (76.09%), bla_CTX-M1 (71.74%), and bla_NDM (67.39%). Two missense mutations in the quinolone resistance-determining region (QRDR) of gyrA (S83L and D87N) and one in both parC (S80I) and parE (S458A) were identified in all isolates, and one in parE (I529L), which had not previously been identified in Bangladesh. These findings suggest that hospital wastewater acts as an important reservoir of antibiotic-resistant bacteria wherein resistance mechanisms to β-lactams and fluoroquinolones are obvious. Our data also emphasize the need for establishing a nationwide surveillance system for antibiotic resistance monitoring to ensure that hospitals sanitize their wastewater before disposal, and regulation to ensure hospital wastewater is kept away from community settings. Full article

(This article belongs to the Section Molecular Microbiology)

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Application of Atmospheric and Room-Temperature Plasma (ARTP) to Microbial Breeding

by Qin Zhang, Renyun Miao, Rencai Feng, Junjie Yan, Tao Wang, Ying Gan, Jin Zhao, Junbin Lin and Bingcheng Gan

Curr. Issues Mol. Biol. 2023, 45(8), 6466-6484; https://doi.org/10.3390/cimb45080408 - 4 Aug 2023

Cited by 21 | Viewed by 3342

Abstract

Atmospheric and room-temperature plasma (ARTP) is an efficient microbial mutagenesis method with broad application prospects. Compared to traditional methods, ARTP technology can more effectively induce DNA damage and generate stable mutant strains. It is characterized by its simplicity, cost-effectiveness, and avoidance of hazardous [...] Read more.

Atmospheric and room-temperature plasma (ARTP) is an efficient microbial mutagenesis method with broad application prospects. Compared to traditional methods, ARTP technology can more effectively induce DNA damage and generate stable mutant strains. It is characterized by its simplicity, cost-effectiveness, and avoidance of hazardous chemicals, presenting a vast potential for application. The ARTP technology is widely used in bacterial, fungal, and microalgal mutagenesis for increasing productivity and improving characteristics. In conclusion, ARTP technology holds significant promise in the field of microbial breeding. Through ARTP technology, we can create mutant strains with specific genetic traits and improved performance, thereby increasing yield, improving quality, and meeting market demands. The field of microbial breeding will witness further innovation and progress with continuous refinement and optimization of ARTP technology. Full article

(This article belongs to the Section Molecular Microbiology)

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Curr. Issues Mol. Biol., Volume 45, Issue 8 (August 2023) – 48 articles

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