Current Issues in Molecular Biology

12 pages, 573 KiB

Open AccessArticle

The Pre-/Post-Transplant Hepatitis C Antibody Associated with the IL-28B RS8099917 TT Genotype and miRNA-122 Expression May Protect Acute Cellular Rejection After LDLT

by King-Wah Chiu, Yu-Cheng Lin, Wei-Feng Li, Kuang-Tzu Huang, Li-Wen Hsu and Chih-Chi Wang

Curr. Issues Mol. Biol. 2024, 46(11), 12772-12783; https://doi.org/10.3390/cimb46110760 (registering DOI) - 10 Nov 2024

Abstract

This study aimed to investigate the relationship between the IL-28B SNP rs8099917 genotype, miRNA-122 expression, and the immune mechanism of ACR after LT using anti-HCV antibody calibration. A total of 45 patients with HCV received LT. IL-28B SNP rs8099917 genotyping was used to [...] Read more.

This study aimed to investigate the relationship between the IL-28B SNP rs8099917 genotype, miRNA-122 expression, and the immune mechanism of ACR after LT using anti-HCV antibody calibration. A total of 45 patients with HCV received LT. IL-28B SNP rs8099917 genotyping was used to divide patients into TT and GT groups. The relative expression levels of miRNA-122 were calculated by quantitative PCR. Anti-HCV titers before and after LT were tracked to observe the relationship with ACR. The ACR rates were 27.6% for genotype TT and 62.5% for genotype GT, indicating a significantly higher rate in the GT group compared to the TT group (p = 0.024). In the rs8099917 genotype, TT was significantly associated with higher serum miRNA-122 levels than GT (p < 0.001). The TT group had significantly better outcomes than the GT group (p = 0.005). The Mann–Whitney U test showed significant differences in pre-LT and post-LT anti-HCV titers between the IL-28B genotypes (TT and GT) (p values of 0.006 and 0.027, respectively). These results suggested that the IL-28B rs8099917 genotype TT may play a significant role in modulating immune responses, both in terms of anti-HCV titers and the risk of ACR, possibly mediated through miRNA-122 levels. Full article

(This article belongs to the Special Issue Advances in Molecular Biology Methods in Hepatology Research)

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3 pages, 175 KiB

Open AccessEditorial

Editorial to the Special Issue “Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies”

by Kinga Lis

Curr. Issues Mol. Biol. 2024, 46(11), 12769-12771; https://doi.org/10.3390/cimb46110759 (registering DOI) - 10 Nov 2024

Abstract

Allergies and other immunity disorders are a current and deepening problem of the modern world, closely related to the progress of civilization [...] Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies)

13 pages, 670 KiB

Open AccessArticle

The Power of WNT5A and FZD3 Gene Expression and Methylation Status in the Diagnosis–Treatment–Cause Triangle in Tension-Type Headache

by Ferhat Kılıçaslan, Sırma Geyik and Şenay Görücü Yılmaz

Curr. Issues Mol. Biol. 2024, 46(11), 12756-12768; https://doi.org/10.3390/cimb46110758 (registering DOI) - 10 Nov 2024

Abstract

DNA methylation is the epigenetic pathway controlling cellular gene expression. Methylation is a natural and cellular epigenetic mechanism for gene silencing. The fact that the genes that the cell decides to be silent do not speak or begin to speak may coincide with [...] Read more.

DNA methylation is the epigenetic pathway controlling cellular gene expression. Methylation is a natural and cellular epigenetic mechanism for gene silencing. The fact that the genes that the cell decides to be silent do not speak or begin to speak may coincide with diseases. For explanatory evidence, changes at the DNA level can provide realistic information. Wnt/β-catenin signaling has an important role in the pain process. For this purpose, we investigated the relationship between clinical data, wingless-type MMTV integration site family, member 5A (WNT5A), and Frizzled Class Receptor 3 (FZD3) gene methylation and expression in a cohort of tension-type headache (TTH) patients (N = 130) and healthy control (N = 117) individuals. Comorbidities were evaluated. Methylation profiling was performed using Real-Time PCR with a TaqMan primer-probe. The diagnostic power (receiver operating characteristic—ROC) was determined according to the expression and methylation status. Ultimately, WNT5A was found to be upregulated and hypermethylated, and FZD3 was found to be upregulated and hypomethylated. Finally, the area under the curve (AUC) data for FZD3 upregulation (0.983) and hypomethylation (0.866) showed diagnostic values. WNT5A and FZD3 may contribute to the pathogenesis of the disease depending on their expression and methylation profile during the TTH process. At the same time, diagnostic powers have the potential to be a resource for early treatment and new therapeutic approaches. Full article

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

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10 pages, 268 KiB

Open AccessReview

Parkinson’s Disease: A Narrative of the Evolving Understanding of the Role of α-Synuclein in Screening

by Alan D. Kaye, Kassady A. Perkinson, Noah J. Spillers, Alexis J. Vega, Caylin J. Roberts, Evan M. Downs, Melissa M. Sheth, David W. McGregor, Jr., Shahab Ahmadzadeh, Jibin Mathew and Sahar Shekoohi

Curr. Issues Mol. Biol. 2024, 46(11), 12746-12755; https://doi.org/10.3390/cimb46110757 (registering DOI) - 10 Nov 2024

Abstract

The present investigation aims to examine the role of α-synuclein seed amplification assays for screening Parkinson’s disease. Parkinson’s disease (PD) is a debilitating neurodegenerative disorder caused by the loss of dopaminergic neurons in the midbrain, leading to symptoms such as tremors, bradykinesia, postural [...] Read more.

The present investigation aims to examine the role of α-synuclein seed amplification assays for screening Parkinson’s disease. Parkinson’s disease (PD) is a debilitating neurodegenerative disorder caused by the loss of dopaminergic neurons in the midbrain, leading to symptoms such as tremors, bradykinesia, postural instability, dementia, and depression. It is classified as an α-synucleinopathy related to the role of α-synuclein aggregates in neuron degeneration. Diagnosis relies on clinical assessment without premortem diagnostic tests or imaging, often resulting in delayed detection and impaired symptom management. In this regard, our study explores a screening technique using an amplification assay to measure α-synuclein levels in cerebrospinal fluid, which could potentially identify early pathological changes and improve diagnostic accuracy and patient outcomes. While preliminary results are promising, further studies are needed to evaluate this approach’s accuracy and clinical feasibility. A review of numerous trials demonstrates that α-synuclein seeding amplification assays (SAA) are a highly reliable, sensitive, and specific diagnostic tool for PD. This assay offers a promising opportunity to improve early diagnosis and quantify severity, especially for asymptomatic individuals or those with a family history of PD, allowing for earlier intervention and more effective disease management. In summary, the emerging body of evidence supporting α-synuclein as a biomarker should allow patients with PD to be detected and treated sooner, enhancing patients’ quality of life and potentially changing the disease trajectory. Full article

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

13 pages, 4141 KiB

Open AccessArticle

Modification of Intestinal Flora Can Improve Host Metabolism and Alleviate the Damage Caused by Chronic Hypoxia

by Zheng Chen, Yang Liao, Shatuo Chai, Yingkui Yang, Qin Ga, Rili Ge, Shuxiang Wang and Shujie Liu

Curr. Issues Mol. Biol. 2024, 46(11), 12733-12745; https://doi.org/10.3390/cimb46110756 (registering DOI) - 10 Nov 2024

Abstract

Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on [...] Read more.

Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on mitigating hypoxic damage. Gut microbiota from high-altitude-adapted species (Ochotona curzoniae) were transplanted into Sprague Dawley (SD) rats, which were then housed in a simulated 6000 m altitude environment for 30 days. After the experiment, we conducted analyses on average daily weight gain (ADG), feed conversion ratio (FCR), mean pulmonary artery pressure (mPAP), gut flora, and fecal metabolism. The results demonstrated that the ADG in the transplantation group (2.98 ± 0.17 g) was significantly higher than in the control groups (2.68 ± 0.19 g and 2.26 ± 0.13 g) (p < 0.05). The FCR was reduced in the transplantation group (6.30 ± 0.33 g) compared to the control groups (8.20 ± 1.15 g and 8.83 ± 0.45 g) (p < 0.05). The mPAP was decreased in the transplantation group (38.1 ± 1.13 mmHg) compared to the control groups (43.4 ± 1.30 mmHg and 43.5 ± 1.22 mmHg) (p < 0.05). Multi-omics analysis revealed that Lachnospiraceae, Desulfovibrionaceae, and specific amino acid metabolic pathways play crucial roles in hypoxia and are associated with both inflammation and nutritional metabolism. This study proposes a novel approach to the treatment of hypoxic pulmonary hypertension and holds potential significance for improving high-altitude developmental potential. Full article

(This article belongs to the Topic Animal Models of Human Disease 2.0)

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15 pages, 881 KiB

Open AccessReview

Molecular Insights into Radiation Effects and Protective Mechanisms: A Focus on Cellular Damage and Radioprotectors

by Blanca Ibáñez, Ana Melero, Alegría Montoro, Nadia San Onofre and Jose M. Soriano

Curr. Issues Mol. Biol. 2024, 46(11), 12718-12732; https://doi.org/10.3390/cimb46110755 (registering DOI) - 9 Nov 2024

Abstract

Ionizing radiation has been a critical tool in various fields, such as medicine, agriculture, and energy production, since its discovery in 1895. While its applications—particularly in cancer treatment and diagnostics—offer significant benefits, ionizing radiation also poses risks due to its potential to cause [...] Read more.

Ionizing radiation has been a critical tool in various fields, such as medicine, agriculture, and energy production, since its discovery in 1895. While its applications—particularly in cancer treatment and diagnostics—offer significant benefits, ionizing radiation also poses risks due to its potential to cause molecular and cellular damage. This damage can occur through the direct ionization of biological macromolecules, such as deoxyribonucleic acid (DNA), or indirectly through the radiolysis of water, which generates reactive oxygen species (ROS) that further damage cellular components. Radioprotectors, compounds that protect against radiation-induced damage, have been extensively researched since World War II. These agents work by enhancing DNA repair, scavenging free radicals, and boosting antioxidant defenses, thereby protecting healthy tissues. Furthermore, some radioprotective agents also stimulate DNA repair mechanisms even after radiation exposure, aiding in recovery from radiation-induced damage. This article explores the molecular mechanisms of radiation-induced damage, focusing on both direct and indirect effects on DNA, and discusses the role of radioprotectors, their mechanisms of action, and recent advancements in the field. The findings underscore the importance of developing effective radioprotective strategies, particularly in medical and industrial settings, where radiation exposure is prevalent. Full article

(This article belongs to the Special Issue Radiation-Induced Cellular and Molecular Responses)

14 pages, 2205 KiB

Open AccessArticle

miR-29a Downregulates PIK3CA Expression and Inhibits Cervical Cancer Cell Dynamics: A Comparative Clinical Analysis

by Hyorim Jeong, Kangchan Choi, Dasom Hwang, Sunyoung Park, Yong Serk Park and Hyeyoung Lee

Curr. Issues Mol. Biol. 2024, 46(11), 12704-12717; https://doi.org/10.3390/cimb46110754 - 8 Nov 2024

Abstract

HPV/pap tests are widely used for cervical cancer screening, playing a crucial role in early diagnosis and guiding future treatment options. However, approximately 50% of cervical cancer patients are diagnosed at an advanced stage, which is associated with higher recurrence rates and poorer [...] Read more.

HPV/pap tests are widely used for cervical cancer screening, playing a crucial role in early diagnosis and guiding future treatment options. However, approximately 50% of cervical cancer patients are diagnosed at an advanced stage, which is associated with higher recurrence rates and poorer survival outcomes than early-stage diagnoses. This underscores the need for effective treatments for advanced-stage cervical cancer. Among the various oncogenes implicated in cancer, PIK3CA expression is known to cause cervical cancer, suggesting that inhibiting PIK3CA may impede cervical cancer progression. In this study, we transfected PIK3CA-overexpressing tumor cells (SiHa, C33A, and HeLa) with miR-29a, a microRNA extensively studied as a therapeutic candidate for oncogene suppression in various tumor types. We conducted RT-qPCR and Western blot analyses to assess changes in PIK3CA expression at the RNA and protein levels. Wound healing and cell migration assays were used to evaluate the effects of miR-29a on cell division and migration in HeLa cells. We confirmed a reduction in PIK3CA expression at both RNA and protein levels following miR-29a transfection. After transfecting miR-29a into HeLa cells, we observed a reduction in cell division and migration, as demonstrated by wound healing and cell migration assays. Additionally, we found that miR-29a binds to the 3′-UTR region of PIK3CA, leading to a reduction in its gene expression. Furthermore, we correlated the concentration of miR-29a in clinical histologic biopsy samples from cervical cancer patients with disease progression. These findings indicate that miR-29a can slow the progression of cervical cancer by targeting PIK3CA and potentially aid in its treatment. miR-29a shows promise as a therapeutic agent for inhibiting oncogene expression and controlling cervical cancer progression, especially in advanced-stage cases. Full article

(This article belongs to the Special Issue Molecular Insights into Pathogenesis and Targeted Therapy of Gynaecological Cancers)

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10 pages, 2740 KiB

Open AccessArticle

Correlation of Eight (8) Polymorphisms and Their Genotypes with the Risk Factors of Cardiovascular Disease in a Black Elderly Population

by Joseph Musonda Chalwe, Christa Johanna Grobler and Wilna Hendrika Oldewage-Theron

Curr. Issues Mol. Biol. 2024, 46(11), 12694-12703; https://doi.org/10.3390/cimb46110753 - 8 Nov 2024

Abstract

Single nucleotide polymorphisms (SNPs) have been associated with the development of cardiovascular diseases (CVDs). This study correlated eight SNPs with the risk factors of CVD in a black elderly population. Genotyping was used to detect eight polymorphisms; rs675 (ApoA-IV), rs699 (Angiotensinogen (AGT)), rs247616 [...] Read more.

Single nucleotide polymorphisms (SNPs) have been associated with the development of cardiovascular diseases (CVDs). This study correlated eight SNPs with the risk factors of CVD in a black elderly population. Genotyping was used to detect eight polymorphisms; rs675 (ApoA-IV), rs699 (Angiotensinogen (AGT)), rs247616 and rs1968905 (Cholesteryl ester transfer protein (CETP)), rs1801278 (Insulin receptor substrate 1 (IRS-1)), rs1805087 (Methylenetetrahydrofolate reductase (MTHFR)) and rs28362286 and rs67608943 (Proprotein convertase subtilisin/kexin type 9 (PCSK9)), as well as their genotypes in deoxyribonucleic acid (DNA) extracted from peripheral blood. The cardiovascular risk (CVR) measurements were conducted on a Konelab 20i Thermo Scientific autoanalyzer and an enzyme-linked immunoassay (ELISA) assay. International Business Machines Corporation (IBM)^® Statistical Package for the Social Sciences ^® (SPSS) version 28 was used for statistical analysis. The heterozygous and homozygous genotypes of the eight polymorphisms were detected with the corresponding CVD risk factors. Subgroup analysis indicated that certain genotype carriers exhibited variations in their concentrations of CVR factors compared to others; however, these differences did not reach statistical significance. For example, carriers of the G genotype of the rs699 polymorphism showed marginally different blood pressure readings compared to the AG genotype carriers. The multiple linear regression analysis indicated that the only significant association was between PCSK9 and the rs28362286 (p = 0.029) polymorphism. The findings of our study show that single nucleotide polymorphisms are disseminated across the human genome. The heterozygous and homozygous genotypes of the SNPs require further investigation as they may have independent and possible collective roles in increasing the risk of CVDs. Full article

(This article belongs to the Special Issue A Focus on the Molecular Basis of Cardiovascular Diseases)

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22 pages, 1242 KiB

Open AccessReview

Intraosseous Delivery of Mesenchymal Stem Cells for the Treatment of Bone and Hematological Diseases

by Mikhail Yu. Artamonov and Evgeniy L. Sokov

Curr. Issues Mol. Biol. 2024, 46(11), 12672-12693; https://doi.org/10.3390/cimb46110752 - 8 Nov 2024

Abstract

Mesenchymal stem cells are used most in regenerative medicine due to their capacities in differentiation and immune modulation. The intraosseous injection of MSC into the bone has been recommended because of expected outcomes for retention, bioavailability, and enhanced therapeutic efficacy, particularly in conditions [...] Read more.

Mesenchymal stem cells are used most in regenerative medicine due to their capacities in differentiation and immune modulation. The intraosseous injection of MSC into the bone has been recommended because of expected outcomes for retention, bioavailability, and enhanced therapeutic efficacy, particularly in conditions involving the bone, such as osteoporosis and osteonecrosis. A review of the intraosseous delivery of mesenchymal stem cells in comparison with intravenous and intra-arterial delivery methods will be subjected to critical examination. This delivery mode fares better regarding paracrine signaling and immunomodulation attributes, which are the cornerstone of tissue regeneration and inflammation reduction. The local complications and technical challenges still apply with this method. This study was more focused on further research soon to be conducted to further elucidate long-term safety and efficacy of intraosseous mesenchymal stem cell therapy. Though much has been achieved with very impressive progress in this field, it is worth noting that more studies need to be put into place so that this technique can be established as a routine approach, especially with further research in biomaterials, gene therapy, and personalized medicine. Full article

(This article belongs to the Special Issue Mesenchymal-Stem-Cell-Based Therapeutic Strategies via Extracellular Vesicles)

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14 pages, 299 KiB

Open AccessReview

Genetics and Molecular Pathogenesis of the Chondrosarcoma: A Review of the Literature

by Georgian-Longin Iacobescu, Antonio-Daniel Corlatescu, Bogdan Serban, Razvan Spiridonica, Horia Petre Costin and Catalin Cirstoiu

Curr. Issues Mol. Biol. 2024, 46(11), 12658-12671; https://doi.org/10.3390/cimb46110751 - 8 Nov 2024

Abstract

The chondrosarcoma, a cartilage-forming bone tumor, presents significant clinical challenges due to its resistance to chemotherapy and radiotherapy. Surgical excision remains the primary treatment, but high-grade chondrosarcomas are prone to recurrence and metastasis, necessitating the identification of reliable biomarkers for diagnosis and prognosis. [...] Read more.

The chondrosarcoma, a cartilage-forming bone tumor, presents significant clinical challenges due to its resistance to chemotherapy and radiotherapy. Surgical excision remains the primary treatment, but high-grade chondrosarcomas are prone to recurrence and metastasis, necessitating the identification of reliable biomarkers for diagnosis and prognosis. This review explores the genetic alterations and molecular pathways involved in chondrosarcoma pathogenesis. These markers show promise in distinguishing between benign enchondromas and malignant chondrosarcomas, assessing tumor aggressiveness, and guiding treatment. While these advancements offer hope for more personalized and targeted therapeutic strategies, further clinical validation of these biomarkers is essential to improve prognostic accuracy and patient outcomes in chondrosarcoma management. Full article

(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer 2024)

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17 pages, 1555 KiB

Open AccessReview

The Connection Between the Oral Microbiota and the Kynurenine Pathway: Insights into Oral and Certain Systemic Disorders

by Rita Kis-György, Tamás Körtési, Alexandra Anicka and Gábor Nagy-Grócz

Curr. Issues Mol. Biol. 2024, 46(11), 12641-12657; https://doi.org/10.3390/cimb46110750 - 7 Nov 2024

Abstract

The oral microbiome, comprising bacteria, fungi, viruses, and protozoa, is essential for maintaining both oral and systemic health. This complex ecosystem includes over 700 bacterial species, such as Streptococcus mutans, which contributes to dental caries through acid production that demineralizes tooth enamel. [...] Read more.

The oral microbiome, comprising bacteria, fungi, viruses, and protozoa, is essential for maintaining both oral and systemic health. This complex ecosystem includes over 700 bacterial species, such as Streptococcus mutans, which contributes to dental caries through acid production that demineralizes tooth enamel. Fungi like Candida and pathogens such as Porphyromonas gingivalis are also significant, as they can lead to periodontal diseases through inflammation and destruction of tooth-supporting structures. Dysbiosis, or microbial imbalance, is a key factor in the development of these oral diseases. Understanding the composition and functions of the oral microbiome is vital for creating targeted therapies for these conditions. Additionally, the kynurenine pathway, which processes the amino acid tryptophan, plays a crucial role in immune regulation, neuroprotection, and inflammation. Oral bacteria can metabolize tryptophan, influencing the production of kynurenine, kynurenic acid, and quinolinic acid, thereby affecting the kynurenine system. The balance of microbial species in the oral cavity can impact tryptophan levels and its metabolites. This narrative review aims to explore the relationship between the oral microbiome, oral diseases, and the kynurenine system in relation to certain systemic diseases. Full article

(This article belongs to the Section Molecular Microbiology)

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8 pages, 869 KiB

Open AccessBrief Report

Impact of Sleeve Gastrectomy on Body Weight and Food Intake Regulation in Diet-Induced Obese Mice

by Sandra Lucinei Balbo, Gabriela Moreira Soares, Joseane Morari, Antonio Machado Felisberto, Jr., Jean Franciesco Vettorazzi, Gabriela Alves Bronczek, Maria Lúcia Bonfleur, Everardo Magalhães Carneiro, Antonio Carlos Boschero and Lício Augusto Velloso

Curr. Issues Mol. Biol. 2024, 46(11), 12633-12640; https://doi.org/10.3390/cimb46110749 - 7 Nov 2024

Abstract

The epidemic of obesity has increased worldwide and is associated with comorbidities such as diabetes and cardiovascular disease. In this context, strategies that modulate body weight and improve glycemic metabolism have increased, and bariatric surgeries such as Sleeve Gastrectomy (SG) have been highlighted [...] Read more.

The epidemic of obesity has increased worldwide and is associated with comorbidities such as diabetes and cardiovascular disease. In this context, strategies that modulate body weight and improve glycemic metabolism have increased, and bariatric surgeries such as Sleeve Gastrectomy (SG) have been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control remains unknown. Thus, in this study, we aimed to evaluate food intake and the expression of hypothalamic genes involved with the regulation of this process in diet-induced obese mice submitted to SG. For this, we used C57BL/6 mice submitted to a 10-week high-fat diet protocol and submitted to SG. Food intake, fed and fasted glycemia, as well as hypothalamic anorexigenic and orexigenic gene expression were evaluated 4 weeks after the surgical procedure. First, we observed that SG reduces body weight (44.19 ± 0.47 HFD, 43.51 ± 0.71 HFD-SHAM, and 38.22 ± 1.31 HFD-SG), fasting glycemia (115.0 ± 4.60 HFD, 122.4 ± 3.48 HFD-SHAM, and 93.43 ± 4.67 HFD-SG), insulinemia (1.77 ± 0.15 HFD, 1.92 ± 0.27 HFD-SHAM, and 0.93 ± 0.05 HFD-SG), and leptinemia (5.86 ± 1.38 HFD, 6.44 ± 1.51 HFD-SHAM, and 1.43 ± 0.35 HFD-SG) in obese mice. Additionally, SG reduces food (5.15 ± 0.18 HFD, 5.49 ± 0.32, HFD-SHAM, and 3.28 ± 0.26 HFD-SG) and total (16.88 ± 0.88 HFD, 17.05 ± 0.42, HFD-SHAM, and 14.30 ± 0.73 HFD-SG) calorie intake without alterations in anorexigenic and orexigenic gene expression. In conclusion, these data indicate that SG improves obesity-associated alterations at least in part by a reduction in food intake. This effect is not associated with the canonical food intake pathway in the hypothalamus, indicating the involvement of non-canonical pathways in this process. Full article

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

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25 pages, 21810 KiB

Open AccessArticle

Morphofunctional Features of Glomeruli and Nephrons After Exposure to Electrons at Different Doses: Oxidative Stress, Inflammation, Apoptosis

by Grigory Demyashkin, Sergey Koryakin, Mikhail Parshenkov, Polina Skovorodko, Matvey Vadyukhin, Zhanna Uruskhanova, Yulia Stepanova, Vladimir Shchekin, Artem Mirontsev, Vera Rostovskaya, Sergey Ivanov, Petr Shegay and Andrei Kaprin

Curr. Issues Mol. Biol. 2024, 46(11), 12608-12632; https://doi.org/10.3390/cimb46110748 - 6 Nov 2024

Abstract

Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, [...] Read more.

Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, the effects of electron radiation on renal tissues remain poorly understood. Given the localized energy deposition of electron beams, this study seeks to investigate the dose-dependent morphological and molecular changes in the kidneys following electron irradiation, aiming to address the gap in knowledge regarding its impact on renal structures. The primary aim of this study is to conduct a detailed morphological and molecular analysis of the kidneys following localized electron irradiation at different doses, to better understand the dose-dependent effects on renal tissue structure and function in an experimental model. Male Wistar rats (n = 75) were divided into five groups, including a control group and four experimental groups receiving 2, 4, 6, or 8 Gray (Gy) of localized electron irradiation to the kidneys. Biochemical markers of inflammation (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF-α]) and oxidative stress (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) were measured, and morphological changes were assessed using histological and immunohistochemical techniques (TUNEL assay, caspase-3). The study revealed a significant dose-dependent increase in oxidative stress, inflammation, and renal tissue damage. Higher doses of irradiation resulted in increased apoptosis, early stages of fibrosis (at high doses), and morphological changes in renal tissue. This study highlights the dose-dependent effects of electrons on renal structures, emphasizing the need for careful consideration of the dosage in clinical use to minimize adverse effects on renal function. Full article

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

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20 pages, 8506 KiB

Open AccessArticle

Gene Delivery via Octadecylamine-Based Nanoparticles for iPSC Generation from CCD1072-SK Fibroblast Cells

by Hanife Sevgi Varlı, Meryem Akkurt Yıldırım, Kadriye Kızılbey and Nelisa Türkoğlu

Curr. Issues Mol. Biol. 2024, 46(11), 12588-12607; https://doi.org/10.3390/cimb46110747 - 6 Nov 2024

Abstract

This study presents a novel biotechnological approach using octadecylamine-based solid lipid nanoparticles (OCTNPs) for the first-time reprogramming of human CCD1072-SK fibroblast cells into induced pluripotent stem cells (iPSCs). OCTNPs, with an average size of 178.9 nm and a positive zeta potential of 22.8 [...] Read more.

This study presents a novel biotechnological approach using octadecylamine-based solid lipid nanoparticles (OCTNPs) for the first-time reprogramming of human CCD1072-SK fibroblast cells into induced pluripotent stem cells (iPSCs). OCTNPs, with an average size of 178.9 nm and a positive zeta potential of 22.8 mV, were synthesized, thoroughly characterized, and utilized as a non-viral vector to efficiently deliver reprogramming factors, achieving a remarkable transfection efficiency of 82.0%. iPSCs were characterized through immunofluorescence, flow cytometry, and RT-qPCR, confirming the expression of key pluripotency markers such as OCT4, SOX2, and KLF4, with alkaline phosphatase activity further validating their pluripotent state. Following this comprehensive characterization, the iPSCs were successfully differentiated into cardiomyocyte-like cells using 5-azacytidine. Our research highlights the innovative application of OCTNPs as a safe and effective alternative to viral vectors, addressing key limitations of iPSC reprogramming. The novel application of OCTNPs for efficient gene delivery demonstrates a powerful tool for advancing stem cell technologies, minimizing risks associated with viral vectors. These findings pave the way for further innovations in biotechnological applications, particularly in tissue engineering and personalized medicine. Full article

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

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14 pages, 1942 KiB

Open AccessArticle

The Role of Cacao Powder in Enhancing Skin Moisture and Reducing Wrinkles: A 12-Week Clinical Trial and In Vitro Study

by Sang Gyu Lee, Ngoc Ha Nguyen, Young In Lee, Inhee Jung, In Ah Kim, Hyunsook Jang, Hoyeon Shin and Ju Hee Lee

Curr. Issues Mol. Biol. 2024, 46(11), 12574-12587; https://doi.org/10.3390/cimb46110746 - 6 Nov 2024

Abstract

Skin aging is driven by a combination of internal and external mechanisms, with ultraviolet (UV) radiation being a prominent external factor contributing to photoaging. Photoaging manifests through several signs, including decreased skin hydration, diminished elasticity, coarse wrinkles, and dyspigmentation. Cacao beans, known for [...] Read more.

Skin aging is driven by a combination of internal and external mechanisms, with ultraviolet (UV) radiation being a prominent external factor contributing to photoaging. Photoaging manifests through several signs, including decreased skin hydration, diminished elasticity, coarse wrinkles, and dyspigmentation. Cacao beans, known for their flavonoids and polyphenols, offer potential anti-aging benefits. To explore this, we conducted a study using both in vitro experiments and clinical trials. Our results demonstrated that cacao powder significantly improved skin hydration and moisture retention in both experimental settings. Specifically, in UVB-damaged human dermal fibroblasts (HDFs) and H₂O₂-treated keratinocytes (KCs), cacao powder displayed notable antioxidant properties. Furthermore, cacao powder enhanced the activity of antioxidant enzymes and promoted the production of hyaluronic acid in KCs, contributing to better skin hydration. It also effectively inhibited the expression of matrix metalloproteinase-1, an enzyme associated with wrinkle formation, and stimulated collagen synthesis in HDFs. Clinical trials conducted on participants with aged skin revealed a significant improvement in skin hydration and a reduction in skin wrinkles after 12 weeks of cacao powder consumption, supporting the in vitro findings. These results suggest that cacao powder holds promise as a natural ingredient for improving skin hydration and reducing wrinkles, underscoring its potential in anti-aging skincare. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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24 pages, 10905 KiB

Open AccessArticle

Benchmark Investigation of SARS-CoV-2 Mutants’ Immune Escape with 2B04 Murine Antibody: A Step Towards Unraveling a Larger Picture

by Karina Kapusta, Allyson McGowan, Santanu Banerjee, Jing Wang, Wojciech Kolodziejczyk and Jerzy Leszczynski

Curr. Issues Mol. Biol. 2024, 46(11), 12550-12573; https://doi.org/10.3390/cimb46110745 - 6 Nov 2024

Abstract

Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. [...] Read more.

Even though COVID-19 is no longer the primary focus of the global scientific community, its high mutation rate (nearly 30 substitutions per year) poses a threat of a potential comeback. Effective vaccines have been developed and administered to the population, ending the pandemic. Nonetheless, reinfection by newly emerging subvariants, particularly the latest JN.1 strain, remains common. The rapid mutation of this virus demands a fast response from the scientific community in case of an emergency. While the immune escape of earlier variants was extensively investigated, one still needs a comprehensive understanding of how specific mutations, especially in the newest subvariants, influence the antigenic escape of the pathogen. Here, we tested comprehensive in silico approaches to identify methods for fast and accurate prediction of antibody neutralization by various mutants. As a benchmark, we modeled the complexes of the murine antibody 2B04, which neutralizes infection by preventing the SARS-CoV-2 spike glycoprotein’s association with angiotensin-converting enzyme (ACE2). Complexes with the wild-type, B.1.1.7 Alpha, and B.1.427/429 Epsilon SARS-CoV-2 variants were used as positive controls, while complexes with the B.1.351 Beta, P.1 Gamma, B.1.617.2 Delta, B.1.617.1 Kappa, BA.1 Omicron, and the newest JN.1 Omicron variants were used as decoys. Three essentially different algorithms were employed: forced placement based on a template, followed by two steps of extended molecular dynamics simulations; protein–protein docking utilizing PIPER (an FFT-based method extended for use with pairwise interaction potentials); and the AlphaFold 3.0 model for complex structure prediction. Homology modeling was used to assess the 3D structure of the newly emerged JN.1 Omicron subvariant, whose crystallographic structure is not yet available in the Protein Database. After a careful comparison of these three approaches, we were able to identify the pros and cons of each method. Protein–protein docking yielded two false-positive results, while manual placement reinforced by molecular dynamics produced one false positive and one false negative. In contrast, AlphaFold resulted in only one doubtful result and a higher overall accuracy-to-time ratio. The reasons for inaccuracies and potential pitfalls of various approaches are carefully explained. In addition to a comparative analysis of methods, some mechanisms of immune escape are elucidated herein. This provides a critical foundation for improving the predictive accuracy of vaccine efficacy against new viral subvariants, introducing accurate methodologies, and pinpointing potential challenges. Full article

(This article belongs to the Special Issue Molecular Biology of Viral Replication and Associated Disease Outcomes)

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23 pages, 790 KiB

Open AccessReview

From Genomic Exploration to Personalized Treatment: Next-Generation Sequencing in Oncology

by Vishakha Vashisht, Ashutosh Vashisht, Ashis K. Mondal, Jana Woodall and Ravindra Kolhe

Curr. Issues Mol. Biol. 2024, 46(11), 12527-12549; https://doi.org/10.3390/cimb46110744 - 6 Nov 2024

Abstract

Next-generation sequencing (NGS) has revolutionized personalized oncology care by providing exceptional insights into the complex genomic landscape. NGS offers comprehensive cancer profiling, which enables clinicians and researchers to better understand the molecular basis of cancer and to tailor treatment strategies accordingly. Targeted therapies [...] Read more.

Next-generation sequencing (NGS) has revolutionized personalized oncology care by providing exceptional insights into the complex genomic landscape. NGS offers comprehensive cancer profiling, which enables clinicians and researchers to better understand the molecular basis of cancer and to tailor treatment strategies accordingly. Targeted therapies based on genomic alterations identified through NGS have shown promise in improving patient outcomes across various cancer types, circumventing resistance mechanisms and enhancing treatment efficacy. Moreover, NGS facilitates the identification of predictive biomarkers and prognostic indicators, aiding in patient stratification and personalized treatment approaches. By uncovering driver mutations and actionable alterations, NGS empowers clinicians to make informed decisions regarding treatment selection and patient management. However, the full potential of NGS in personalized oncology can only be realized through bioinformatics analyses. Bioinformatics plays a crucial role in processing raw sequencing data, identifying clinically relevant variants, and interpreting complex genomic landscapes. This comprehensive review investigates the diverse NGS techniques, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and single-cell RNA sequencing (sc-RNA-Seq), elucidating their roles in understanding the complex genomic/transcriptomic landscape of cancer. Furthermore, the review explores the integration of NGS data with bioinformatics tools to facilitate personalized oncology approaches, from understanding tumor heterogeneity to identifying driver mutations and predicting therapeutic responses. Challenges and future directions in NGS-based cancer research are also discussed, underscoring the transformative impact of these technologies on cancer diagnosis, management, and treatment strategies. Full article

(This article belongs to the Special Issue Technological Advances around Next-Generation Sequencing Application)

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15 pages, 5546 KiB

Open AccessArticle

Effect of Soy Isoflavone on Prostate Cancer Cell Apoptosis Through Inhibition of STAT3, ERK, and AKT

by Yoon-Jin Lee, Changyeol Lee, Dongsic Choi, Yeji Lee and Sang-Han Lee

Curr. Issues Mol. Biol. 2024, 46(11), 12512-12526; https://doi.org/10.3390/cimb46110743 - 6 Nov 2024

Abstract

Genistein, an isoflavone found in soybeans, exhibits antioxidant, anti-inflammatory, and anticancer properties. This study explored the molecular mechanisms behind genistein’s anticancer effects in prostate cancer DU145 cells. In this study, genistein decreased cell viability, increased annexin V-PE(+) cells, and enhanced the sub-G₀ [...] Read more.

Genistein, an isoflavone found in soybeans, exhibits antioxidant, anti-inflammatory, and anticancer properties. This study explored the molecular mechanisms behind genistein’s anticancer effects in prostate cancer DU145 cells. In this study, genistein decreased cell viability, increased annexin V-PE(+) cells, and enhanced the sub-G₀/G₁ peak by flow cytometric analysis. Increased reactive oxygen species increased mitochondrial depolarization indicating mitochondrial dysfunction and inhibition of ATP formation were also observed in genistein-treated DU145 cells. Genistein upregulated p53 at the mRNA and protein levels and increased caspase-3/7 activity along with the cleavage of Bax, procaspase-3, and PARP. With the increasing genistein concentrations, the percentage of cells in the sub-G₀/G₁ peak and G₂/M phase increased, which was inhibited by treatment with the pan-caspase inhibitor Z-VAD together with 100 μM genistein, which had little toxicity to normal prostate epithelial HPrEC cells. Genistein treatment simultaneously inhibited the activation of STAT3 and other closely related oncogenic kinases such as AKT and ERK and p38 and decreased VEGF expression. Taken together, these results suggest that genistein inhibits the growth of DU145 cells and induces apoptosis by inhibiting STAT3, AKT, ERK, and p38 which provides a molecular basis for the anticancer activity of genistein and suggests its potential as a valuable therapeutic candidate for prostate cancer. Full article

(This article belongs to the Special Issue Molecular Insights into Food-Derived Natural Products and Their Biological Activities)

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15 pages, 2242 KiB

Open AccessArticle

Curcumin Mitigates Muscle Atrophy Potentially by Attenuating Calcium Signaling and Inflammation in a Spinal Nerve Ligation Model

by Casey Appell, Nigel C. Jiwan, Chwan-Li Shen and Hui-Ying Luk

Curr. Issues Mol. Biol. 2024, 46(11), 12497-12511; https://doi.org/10.3390/cimb46110742 - 5 Nov 2024

Abstract

Denervation-induced calcium/calmodulin-dependent protein kinase II (CaMKII) activation and inflammation can result in muscle atrophy. Curcumin and bisdemethoxycurcumin are well known to exhibit an anti-inflammatory effect. In addition, curcumin has been shown to attenuate CaMKII activation in neuronal cells. This study aimed to examine [...] Read more.

Denervation-induced calcium/calmodulin-dependent protein kinase II (CaMKII) activation and inflammation can result in muscle atrophy. Curcumin and bisdemethoxycurcumin are well known to exhibit an anti-inflammatory effect. In addition, curcumin has been shown to attenuate CaMKII activation in neuronal cells. This study aimed to examine the effect of curcumin or bisdemethoxycurcumin on CaMKII activation, inflammation, and muscle cross-sectional area (CSA) in spinal nerve ligated rats. Sixteen female rats were assigned to sham (CON), spinal nerve ligation (SNL), SNL+ curcumin 100 mg/kg BW (100CUR), and SNL+ bisdemethoxycurcumin 50 mg/kg BW (50CMO) for 4 weeks. Ipsilateral (surgical) soleus and tibialis anterior (TA) muscles was stained for dystrophin to measure CSA. Ipsilateral and contralateral (non-surgical) plantaris muscles were analyzed for protein content for acetylcholine receptor (AChR), CaMKII, CaMKII^Thr286, nuclear factor-κB (NF-κB), NF-κB^Ser536, and interleukin-1β (IL-1β) and normalized to α-tubulin and then CON. A significant (p < 0.050) group effect was observed for TA CSA where CON (11,082.25 ± 1617.68 μm²; p < 0.001) and 100CUR (9931.04 ± 2060.87 μm²; p = 0.018) were larger than SNL (4062.25 ± 151.86 μm²). In the ipsilateral plantaris, the SNL (4.49 ± 0.69) group had greater CaMKII activation compared to CON (1.00 ± 0.25; p = 0.010), 100CUR (1.12 ± 0.45; p = 0.017), and 50CMO (0.78 ± 0.19; p = 0.009). The ipsilateral plantaris (2.11 ± 0.66) had greater IL-1β protein content than the contralateral leg (0.65 ± 0.14; p = 0.041) in the SNL group. In plantaris, the SNL (1.65 ± 0.51) group had greater NF-κB activation compared to CON (1.00 ± 0.29; p = 0.021), 100CUR (0.61 ± 0.10; p = 0.003), 50CMO (0.77 ± 0.25; p = 0.009) groups. The observed reduction in Ca²⁺ signaling and inflammation in type II plantaris muscle fibers might reflect the changes within the type II TA muscle fibers which may contribute to the mitigation of TA mass loss with curcumin supplementation. Full article

(This article belongs to the Special Issue Pharmacological Activities and Mechanisms of Action of Natural Products)

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