Current Issues in Molecular Biology

16 pages, 3422 KiB

Open AccessArticle

Evidence to Support the Collaboration of SP1, MYC, and HIF1A and Their Association with microRNAs

by Jong Ho Chun, Kotohiko Kimura, Monika Rajput, Ming-Hua Hsu, Yu-Chuan Liang, Akanksha Ramadas Shanbhag, Pei-Ju Chiang, Tiffany L. B. Jackson and Ru Chih C. Huang

Curr. Issues Mol. Biol. 2024, 46(11), 12481-12496; https://doi.org/10.3390/cimb46110741 (registering DOI) - 5 Nov 2024

Abstract

This study provides evidence to support the concept proposed by Kimura et al. in 2023 that the inhibitors of SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins. In LN229 and U87MG glioblastoma cells, either [...] Read more.

This study provides evidence to support the concept proposed by Kimura et al. in 2023 that the inhibitors of SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins. In LN229 and U87MG glioblastoma cells, either tetra-methyl-O-nordihydroguaiaretic acid (M₄N) or tetra-acetyl-O-nordihydroguaiaretic acid (A₄N) suppressed SP1 and only a few stem cell-related proteins and induced only a small amount of cell death; in contrast, the combination treatment of M₄N with A₄N greatly suppressed the expression of SP1, MYC, and HIF1A, as well as all of the stem cell-related proteins examined, and greatly induced cell death. The bioinformatic analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various microRNAs (miRNAs) that had been shown to induce either anti- or procancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate the transcription of both coding and noncoding RNAs and affect cancers. These data overall supported our concept. Full article

(This article belongs to the Special Issue The 25th Anniversary of CIMB: Perspectives in Molecular Biology)

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24 pages, 3599 KiB

Open AccessArticle

Complementary Treatment of Breast Cancer Cells with Different Metastatic Potential with Iscador Qu in the Presence of Clinically Approved Anticancer Drugs

by Ivan Iliev, Iana Tsoneva, Aleksandrina Nesheva, Galya Staneva, Bozhil Robev, Albena Momchilova and Biliana Nikolova

Curr. Issues Mol. Biol. 2024, 46(11), 12457-12480; https://doi.org/10.3390/cimb46110740 (registering DOI) - 5 Nov 2024

Abstract

European mistletoe extract (Iscador Qu) has been studied for decades, but it has not ceased to arouse scientific interest. The purpose was to investigate the impact of Iscador Qu on the antiproliferative potential of 11 standard chemotherapeutic agents on two breast cancer cell [...] Read more.

European mistletoe extract (Iscador Qu) has been studied for decades, but it has not ceased to arouse scientific interest. The purpose was to investigate the impact of Iscador Qu on the antiproliferative potential of 11 standard chemotherapeutic agents on two breast cancer cell lines: MCF-7 low-metastatic and MDA-MB-231 high-metastatic and control cell lines (MCF-10A). MTT-dye reduction assay, FACS analysis, and PI staining were utilized. The most promising combinations acting against the MDA-MB-231 cell line were observed upon the simultaneous application of Iscador Qu (80 µg/mL) and Docetaxel, with 4-fold reduction in IC₅₀. An antagonistic effect was found under treatment with Cisplatin and Iscador Qu (1.5-fold increase in IC₅₀). The response of the low-metastatic breast cancer cell line MCF-7 to the tested combinations was different compared to the high-metastatic one. The most pronounced cytotoxic effect was found for the combination of Oxaliplatin and Iscador Qu (20 µg/mL) (5.2-fold IC₅₀ reduction). An antagonistic effect for MCF-7 line was also observed when combinations with Olaparib and Tamoxifen were applied. This in vitro study offers new combinations between Iscador Qu and standard chemotherapeutic agents that hold great promise in establishing breast cancer therapeutic protocols compared to traditional monotherapies. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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15 pages, 2713 KiB

Open AccessArticle

Comparative Analysis of Two Soybean Cultivars Revealed Tolerance Mechanisms Underlying Soybean Adaptation to Flooding

by Xiaobo Yu, Jiangang An, Jianqiu Liang, Wenying Yang, Zhaoqiong Zeng, Mingrong Zhang, Haiying Wu, Sichen Liu and Xiaoning Cao

Curr. Issues Mol. Biol. 2024, 46(11), 12442-12456; https://doi.org/10.3390/cimb46110739 (registering DOI) - 4 Nov 2024

Abstract

Flooding stress poses a significant challenge to soybean cultivation, impacting plant growth, development, and ultimately yield. In this study, we investigated the responses of two distinct soybean cultivars: flooding-tolerant Nanxiadou 38 (ND38) and flooding-sensitive Nanxiadou 45 (ND45). To achieve this, healthy seedlings were [...] Read more.

Flooding stress poses a significant challenge to soybean cultivation, impacting plant growth, development, and ultimately yield. In this study, we investigated the responses of two distinct soybean cultivars: flooding-tolerant Nanxiadou 38 (ND38) and flooding-sensitive Nanxiadou 45 (ND45). To achieve this, healthy seedlings were cultivated with the water surface consistently maintained at 5 cm above the soil surface. Our objective was to elucidate the physiological and molecular adaptations of the two cultivars. Under flooding stress, seedlings of both cultivars exhibited significant dwarfing and a notable decrease in root length. While there were no significant differences in the dry weight of aboveground shoots, the dry weight of underground shoots in ND38 was strikingly decreased following flooding. Additionally, total chlorophyll content decreased significantly following flooding stress, indicating impaired photosynthetic performance of the cultivars. Moreover, malondialdehyde (MDA) levels increased significantly after flooding, particularly in the ND45 cultivar, suggesting heightened oxidative stress. Expression analysis of methylation and demethylation genes indicated that MET1 and DME play crucial roles in response to flooding stress in soybeans. Meanwhile, analysis of the hemoglobin family (GLBs), aquaporin family (AQPs), glycolytic pathway-related genes, and NAC transcription factor-related genes identified GLB1-1 and GLB1-2, GLB2-2, PIP2-6, PIP2-7, TIP2-2, TIP4-1, TIP5-1, Gm02G222400 (fructose-bisphosphate aldolase), Gm19G017200 (glucose-6-phosphate isomerase), and Gm04G213900 (alcohol dehydrogenase 1) as key contributors to flooding tolerance in both soybean cultivars. These findings provide crucial insights into the physiological and molecular mechanisms underlying flooding tolerance in soybeans, which could guide future molecular breeding strategies for the development of flooding-tolerant soybean cultivars. Full article

(This article belongs to the Section Molecular Plant Sciences)

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14 pages, 2407 KiB

Open AccessArticle

Low, but Not High, Pulsating Fluid Shear Stress Affects Matrix Extracellular Phosphoglycoprotein Expression, Mainly via Integrin β Subunits in Pre-Osteoblasts

by Jianfeng Jin and Behrouz Zandieh-Doulabi

Curr. Issues Mol. Biol. 2024, 46(11), 12428-12441; https://doi.org/10.3390/cimb46110738 (registering DOI) - 4 Nov 2024

Abstract

Matrix extracellular phosphoglycoprotein (Mepe), present in bone and dentin, plays important multifunctional roles in cell signaling, bone mineralization, and phosphate homeostasis. Mepe expression in bone cells changes in response to pulsating fluid shear stress (PFSS), which is transmitted into cells through integrin-based adhesion [...] Read more.

Matrix extracellular phosphoglycoprotein (Mepe), present in bone and dentin, plays important multifunctional roles in cell signaling, bone mineralization, and phosphate homeostasis. Mepe expression in bone cells changes in response to pulsating fluid shear stress (PFSS), which is transmitted into cells through integrin-based adhesion sites, i.e., α and β subunits. Whether and to what extent PFSS influences Mepe expression through the modulation of integrin α and/or β subunit expression in pre-osteoblasts is uncertain. Therefore, we aimed to test whether low and/or high PFSS affects Mepe expression via modulation of integrin α and/or β subunit expression. MC3T3-E1 pre-osteoblasts were treated with ± 1 h PFSS (magnitude: 0.3 Pa (low PFSS) or 0.7 Pa (high PFSS); frequency: 1 Hz). Single integrin fluorescence intensity in pre-osteoblasts was increased, but single integrin area was decreased by low and high PFSS. Expression of two integrin α subunit-related genes (Itga1 and Itga5 2) was increased by low PFSS, and one (Itga5 2) by high PFSS. Expression of five integrin β subunit genes (Itgb1, Itgb3, Itgb5, Itgb5 13, and Itgb5 123) was increased by low PFSS, and three (Itgb5, Itgb5 13, and Itgb5 123) by high PFSS. Interestingly, Mepe expression in pre-osteoblasts was only modulated by low, but not high, PFSS. In conclusion, both low and high PFSS affected integrin α and β subunit expression in pre-osteoblasts, while integrin β subunit expression was more altered by low PFSS. Importantly, Mepe gene expression was only affected by low PFSS. These results might explain the different ways that Mepe-induced changes in pre-osteoblast mechanosensitivity may drive signaling pathways of bone cell function at low or high impact loading. These findings might have physiological and biomedical implications and require future research specifically addressing the precise role of integrin α or β subunits and Mepe during dynamic loading in bone health and disease. Full article

(This article belongs to the Special Issue Osteoclastogenesis and Osteogenesis: Physiological and Molecular Responses to Xenobiotics and Biomaterials)

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11 pages, 1679 KiB

Open AccessArticle

Empagliflozin Attenuates High-Glucose-Induced Astrocyte Activation and Inflammation via NF-κB Pathway

by Dong Hee Kim, Min Jin Lee, Dasol Kang, Ji Young Lee, Sujin Park, Ah Reum Khang, Ji Hyun Bae, Joo Yeon Kim, Su Hyun Kim, Yang Ho Kang and Dongwon Yi

Curr. Issues Mol. Biol. 2024, 46(11), 12417-12427; https://doi.org/10.3390/cimb46110737 (registering DOI) - 4 Nov 2024

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its [...] Read more.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its roles in the central nervous system are unclear. This study investigated the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic inflammation associated with metabolic diseases. Mice were subjected to a high-fat diet (HFD) for varying durations (3 d, 3 weeks, and 16 weeks) and treated with EMPA for 3 weeks (NFD, NFD + EMPA, HFD, HFD + EMPA; n = 5/group). EMPA regulated the expression of astrocyte markers and pro-inflammatory cytokine mRNA in the hypothalamus of HFD-induced mice, which was linked to regulation of the NF-κB pathway. Under hyperglycemic conditions, EMPA may mitigate hypothalamic inflammation by modulating astrocyte activation via the NF-κB pathway. Our findings demonstrated that EMPA possesses therapeutic potential beyond merely lowering blood glucose levels, opening new avenues for addressing inflammation and providing neuroprotection in metabolic disease management. Full article

(This article belongs to the Special Issue The Role of Neuroinflammation in Neurodegenerative Diseases)

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20 pages, 2794 KiB

Open AccessArticle

Establishing a Female Animal Model of Prediabetes Using a High-Carbohydrate, High-Fat Diet

by Ayanda Nkosi, Reveshni Pather, Bongeka Mshengu, Andile Khathi and Phikelelani Ngubane

Curr. Issues Mol. Biol. 2024, 46(11), 12397-12416; https://doi.org/10.3390/cimb46110736 (registering DOI) - 3 Nov 2024

Abstract

Prediabetes is a condition that often precedes the onset of type 2 diabetes and is characterized by moderate levels of insulin resistance. This condition is well established in male animal models for diabetes; however, few female models exist. There is accumulating evidence that [...] Read more.

Prediabetes is a condition that often precedes the onset of type 2 diabetes and is characterized by moderate levels of insulin resistance. This condition is well established in male animal models for diabetes; however, few female models exist. There is accumulating evidence that sex variations affect the pathogenesis, treatment, and consequences of numerous diseases, such as type 2 diabetes. Therefore, we sought to develop a diet-induced prediabetic female animal model to better understand prediabetes development and its effects in females. Female Sprague Dawley rats were randomly allocated to one of two groups: the standard diet (SD) group fed a standard diet with normal drinking water, and the high-carbohydrate, high-fat (HCHF) group fed a high-carbohydrate and high-fat diet with drinking water supplemented with fructose. During induction, we measured food intake, body weight, body mass index (BMI), and oral glucose tolerance response (OGT). After the induction period, biochemical analyses were conducted to assess the levels of plasma leptin, ghrelin, insulin, and glycated hemoglobin (HbA1c). Glycogen concentrations were quantified in the liver and skeletal muscles. The HCHF diet-fed group presented higher body weight gain, food intake, and BMI levels, which were accompanied by elevated plasma insulin, ghrelin, and liver and skeletal muscle glycogen levels compared to the SD-fed group. In the HCHF diet-fed group, the HOMA-IR was above 1.9, suggesting the presence of moderate levels of insulin resistance. The OGT response was significantly higher in the HCHF-fed group versus the SD-fed group, suggesting impaired glucose tolerance, thus displaying the signs and symptoms of prediabetes. The HCHF diet with fructose led to the induction of prediabetes in female Sprague Dawley rats. This model could be used to investigate and outline the pathophysiological complications associated with prediabetes in females as a result of the prolonged ingestion of a high carbohydrate, high-fat diet with fructose. The development of this model could also serve as an effort to further bridge the gap regarding the inclusion of females in biomedical research, thus providing advancements in deriving better, specified treatment strategies for women. Full article

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

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22 pages, 3389 KiB

Open AccessArticle

A Study of the Bioactive Compounds, Antioxidant Capabilities, Antibacterial Effectiveness, and Cytotoxic Effects on Breast Cancer Cell Lines Using an Ethanolic Extract from the Aerial Parts of the Indigenous Plant Anabasis aretioïdes Coss. & Moq.

by Salah Laaraj, Aziz Tikent, Mohamed Chebaibi, Khawla Bouaouda, Mohamed Bouhrim, Sherouk Hussein Sweilam, Rashed N. Herqash, Abdelaaty A. Shahat, Mohamed Addi and Kaoutar Elfazazi

Curr. Issues Mol. Biol. 2024, 46(11), 12375-12396; https://doi.org/10.3390/cimb46110735 (registering DOI) - 1 Nov 2024

Abstract

Anabasis aretioïdes contain numerous bioactive compounds that provide several advantages, including antioxidant, antibacterial, anticancer, neuroprotective, anti-inflammatory, and antidiabetic characteristics. This study aimed to make a hydroethanolic extract from the aerial part of the plant, analyze its biochemical compounds, and test its biological activities. [...] Read more.

Anabasis aretioïdes contain numerous bioactive compounds that provide several advantages, including antioxidant, antibacterial, anticancer, neuroprotective, anti-inflammatory, and antidiabetic characteristics. This study aimed to make a hydroethanolic extract from the aerial part of the plant, analyze its biochemical compounds, and test its biological activities. From HPLC-DAD analysis, cinnamic acid, sinapic acid, and vanillin bioactives were found to be the main compounds in the extract. The spectrometric tests revealed that the extract was rich in flavonoids (8.52 ± 0.32 mg RE/100 g DW), polyphenols (159.32 ± 0.63 mg GAE/100 g DW), and condensed tannins (8.73 ± 0.23 mg CE/100 g DW). The extract showed significant antioxidant activity. There were strong correlations between the amount of flavonoid or polyphenol and the antioxidant assays, including ABTS, DPPH, β-carotene, and TAC. The extract also showed highly effective results against Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis as well as against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, and showed promising cytotoxicity against breast cancer cell lines MCF-7 and MDA-MB-231. The in silico modeling of the bioactive compounds contained in the extract illustrated their interaction mode with the active sites of particular target proteins, and it showed that rutin had the strongest effect on stopping NADPH oxidase enzyme, with a glide score of −6.889 Kcal/mol. Sinapic acid inhibited E. coli beta-ketoacyl-[acyl carrier protein] synthase (−7.517 kcal/mol), and apigenin showed high binding affinity to S. aureus nucleoside di-phosphate kinase, with −8.656 kcal/mol. Succinic acid has the strongest anticancer effect for caspase-3, with a glide score of −8.102 kcal/mol. These bioactive components may be beneficial as antioxidant and antibacterial applications in medicine, foods, natural cosmetics, and breast cancer prevention in the future. As a result, the use of this indigenous plant must be considered to maximize its value and preservation. Full article

(This article belongs to the Special Issue Biochemical Composition and Activity of Medicinal Plants and Food)

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21 pages, 1928 KiB

Open AccessArticle

Comprehensive Safety Assessment of Lacticaseibacillus paracasei subsp. paracasei NTU 101 Through Integrated Genotypic and Phenotypic Analysis

by Chieh-Ting Chen, Wen-Yu Chao, Chih-Hui Lin, Tsung-Wei Shih and Tzu-Ming Pan

Curr. Issues Mol. Biol. 2024, 46(11), 12354-12374; https://doi.org/10.3390/cimb46110734 (registering DOI) - 1 Nov 2024

Abstract

Probiotics, as defined by the World Health Organization, are live microorganisms that, when consumed in sufficient quantities, provide health benefits to the host. Although some countries have approved specific probiotic species for use in food, safety concerns may still arise with individual strains. [...] Read more.

Probiotics, as defined by the World Health Organization, are live microorganisms that, when consumed in sufficient quantities, provide health benefits to the host. Although some countries have approved specific probiotic species for use in food, safety concerns may still arise with individual strains. Lacticaseibacillus paracasei subsp. paracasei NTU 101 (NTU 101), isolated from the gut of healthy infants, has demonstrated various probiotic effects and shown safety in a prior 28-day animal feeding study. To further verify its safety and mitigate potential risks, we performed a comprehensive genotypic and phenotypic safety evaluation in accordance with the European Food Safety Authority guidelines for safety assessment through whole genome sequencing and related literature. In this research, minimum inhibitory concentration testing identified NTU 101’s resistance to chloramphenicol; however, subsequent gene analysis confirmed no associated risk of resistance. Assessments of safety, including biogenic amine content, hemolytic activity, mucin degradation, and D-lactic acid production, indicated a low level of risk. Additionally, a repeated-dose 90-day oral toxicity study in Sprague-Dawley rats revealed no toxicity at a dose of 2000 mg/kg body weight, further supporting the strain’s safety for consumption. Based on these comprehensive analyses, NTU 101 is considered safe for regular consumption as a health supplement. Full article

(This article belongs to the Section Molecular Microbiology)

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11 pages, 2247 KiB

Open AccessArticle

Impact of Opuntia ficus-indica Juice and Empagliflozin on Glycemic Control in Rats

by Sondos M. Alqudah, Mohammad Hailat, Zainab Zakaraya, Alaa Azeez Abu Dayah, Mohammad Abu Assab, Samia M. Alarman, Riad M. Awad, Mohammed F. Hamad, Laura Grațiela Vicaș and Wael Abu Dayyih

Curr. Issues Mol. Biol. 2024, 46(11), 12343-12353; https://doi.org/10.3390/cimb46110733 (registering DOI) - 1 Nov 2024

Abstract

Diabetes mellitus (DM) is a major global health concern characterized by high blood glucose levels. This study investigates the effects of Opuntia ficus-indica (cactus) juice and empagliflozin, both alone and in combination, on glycated hemoglobin (HbA1c) levels in healthy and streptozotocin-induced diabetic rats. [...] Read more.

Diabetes mellitus (DM) is a major global health concern characterized by high blood glucose levels. This study investigates the effects of Opuntia ficus-indica (cactus) juice and empagliflozin, both alone and in combination, on glycated hemoglobin (HbA1c) levels in healthy and streptozotocin-induced diabetic rats. Eighty Wistar albino male rats were divided into eight groups, with four groups being diabetic. Treatment options included cactus juice, empagliflozin, or both. HbA1c levels were measured at baseline and 100 days later using ELISA. In diabetic and non-diabetic rats treated with cactus juice or empagliflozin, HbA1c levels were significantly reduced, but diabetic rats had significantly lower HbA1c values than non-diabetic rats. The combined treatment provided no additional benefits over individual therapies. These findings indicate that cactus juice and empagliflozin effectively lower HbA1c levels, making their use a promising complementary approach to diabetes management. However, the combined treatment of Opuntia ficus-indica juice and empagliflozin did not yield additional reductions in HbA1c levels compared to individual treatments, with no significant synergistic effects observed throughout the study period. More research is needed to better understand the clinical applications and mechanisms in humans. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products, 2nd Edition)

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21 pages, 4909 KiB

Open AccessReview

Utilizing Flaxseed as an Antimicrobial Alternative in Chickens: Integrative Review for Salmonella enterica and Eimeria

by William C. Weston, Karen H. Hales and Dale B. Hales

Curr. Issues Mol. Biol. 2024, 46(11), 12322-12342; https://doi.org/10.3390/cimb46110732 (registering DOI) - 31 Oct 2024

Abstract

This review provides an integrative framework for understanding flaxseed (Linum utassitissimum) as an antimicrobial alternative for poultry production. We begin by familiarizing the reader with the global legislation of antibiotics in animal husbandry; highlighting gaps and current issues for Salmonella enterica [...] Read more.

This review provides an integrative framework for understanding flaxseed (Linum utassitissimum) as an antimicrobial alternative for poultry production. We begin by familiarizing the reader with the global legislation of antibiotics in animal husbandry; highlighting gaps and current issues for Salmonella enterica (S. enterica) and Eimeria (coccidiosis-inducing). We then discuss the natural, symbiotic characteristics of the Galliformes order (chicken-like birds) and Linum (the flaxes). The key immunological themes in this review include: (i) flaxseed’s regulation of innate and adaptive immunity in chickens, (ii) flaxseed’s ability to accelerate chicken recovery from infection with S. enterica and Eimeria, and (iii) flaxseed’s strengthening of immunity via vitamin B6 antagonism. Research indicates that whole flaxseed increases adaptive immune capacity by augmenting cecal Bacteroides and short-chain fatty acids while also attenuating the heterophil to lymphocyte ratio in chickens. Moreover, flaxseed accelerates chicken recovery from infection with Salmonella Enteritidis or Eimeria tenella; however, future work is needed to better understand (i) defatted flaxseed’s superior performance against Eimeria species and (ii) Eimeria maxima’s resilience against whole flaxseed. In the context of vitamin B6 antagonism, we propose that 15% whole flaxseed overcomes S. enterica’s insult to estrogen synthesis by sustaining the activity of phosphatidylethanolamine methyltransferase (PEMT) in liver. We also propose that 10% defatted flaxseed (as a metformin homologue) strengthens chicken immunity by safeguarding gonadal physiology and by increasing plasma thymidine bioavailability. The concepts in this review can be used as a template for conducting advanced immunological studies in poultry science. Full article

(This article belongs to the Special Issue Molecular Research in Food Science)

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11 pages, 1732 KiB

Open AccessArticle

Two-Sample Mendelian Randomization Study Identifies Tissue-Dependent Risk Genes in Autoimmune Diseases

by Ryan Chiu and Li Ma

Curr. Issues Mol. Biol. 2024, 46(11), 12311-12321; https://doi.org/10.3390/cimb46110731 (registering DOI) - 31 Oct 2024

Abstract

Autoimmune diseases are among the most prevalent diseases across the world with genetic and environmental factors that contribute to their etiology. Because the exact causes of autoimmune diseases are largely unknown, a Mendelian randomization (MR) approach is used here to examine the potential [...] Read more.

Autoimmune diseases are among the most prevalent diseases across the world with genetic and environmental factors that contribute to their etiology. Because the exact causes of autoimmune diseases are largely unknown, a Mendelian randomization (MR) approach is used here to examine the potential causal association between gene expression levels and disease risk across various tissues. Specifically, this study focuses on six autoimmune diseases including Crohn’s disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus. Several of these diseases are currently treatable with immunosuppressants that target specific genes, such as TNF-alpha, IL-23, CD20, and more. In this study, a two-sample MR analysis is performed with multitissue expression quantitative trait loci (eQTLs) and large-scale genome-wide association studies to investigate how gene expression can influence the risk of developing these diseases. Our results show that genes HLA-DQA1/2, HLA-DRB1/6, HLA-DQB2, C4A, CYP21A2, and HLA-DQB1-AS1 have a high causal effect across several diseases and tissues, and almost all of these findings originate from the major histocompatibility complex (MHC) region on Chromosome 6. Our findings support the current knowledge of genes associated with these diseases while also revealing novel genes that can be used for drug therapies in the future. Although several drug therapies currently exist to treat this selection of autoimmune diseases, we provide further insights into the main, common pathways responsible for autoimmune disease pathogenesis and discuss novel genes that lack research focus. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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12 pages, 3771 KiB

Open AccessArticle

The Effect of Geranylgeraniol and Ginger on Satellite Cells Myogenic State in Type 2 Diabetic Rats

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

Curr. Issues Mol. Biol. 2024, 46(11), 12299-12310; https://doi.org/10.3390/cimb46110730 (registering DOI) - 31 Oct 2024

Abstract

Type 2 diabetes (T2D) is associated with increased inflammation and reactive oxygen species (ROS) in muscles, leading to basal satellite cell (SC) myogenic impairment (i.e., reduction in SC pool), which is critical for maintaining skeletal muscle mass. T2D may contribute to muscle atrophy, [...] Read more.

Type 2 diabetes (T2D) is associated with increased inflammation and reactive oxygen species (ROS) in muscles, leading to basal satellite cell (SC) myogenic impairment (i.e., reduction in SC pool), which is critical for maintaining skeletal muscle mass. T2D may contribute to muscle atrophy, possibly due to reductions in the SC pool. Geranylgeraniol (GGOH) and ginger can reduce inflammation and enhance SC myogenesis in damaged muscles, thereby alleviating muscle atrophy; however, their effect on basal SC myogenic state and muscle mass in T2D rats is limited. Rats consumed a control diet (CON), high-fat diet with 35 mg/kg of streptozotocin (HFD), a HFD with 800 mg/kg body weight of GGOH (GG), or a HFD with 0.75% ginger root extract (GRE). In the eighth week, their soleus muscles were analyzed for Pax7, MyoD, and MSTN gene and protein expression, SC myogenic state, and muscle cross-sectional area (CSA). The HFD group had a significantly lower number of Pax7⁺/MyoD⁻ and Pax7⁺/MSTN⁺ cells, less Pax7 and MyoD gene expression, and less MyoD and MSTN protein expression, with a smaller CSA than the CON group. Compared to the GG and GRE groups, the HFD group had a significantly lower number of Pax7⁺/MSTN⁺ cells, less MyoD protein expression, and smaller CSA. The GRE group also had a significantly lower number of Pax7⁻/MyoD⁺ and greater MSTN protein expression than the HFD group. Nevertheless, the CON group had a significantly greater number of Pax7⁺/MyoD⁻ than the GG and GRE groups, and a greater number of Pax7⁻/MyoD⁺ cells than the GRE group with a larger CSA than the GG group. GGOH and ginger persevered muscle CSA, possibly through increased MyoD and the ability to maintain the SC pool in T2D rats. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds, 2nd Edition)

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20 pages, 6007 KiB

Open AccessArticle

Integrative Taxonomy Reveals New Insights into the Species Validity of the Neocaridina davidi-N. denticulata-N. heteropoda Complex and Mitogenomic Phylogeny of Caridean Shrimps

by Mei Yang, Xiaodong Cui, Xinzheng Li, Dong Dong, Xianjiang Kang and Zhibin Gan

Curr. Issues Mol. Biol. 2024, 46(11), 12279-12298; https://doi.org/10.3390/cimb46110729 (registering DOI) - 31 Oct 2024

Abstract

The genus Neocaridina, originating from East Asia and representing a small-size landlocked shrimp group of the family Atyidae, is an important group of ornamental shrimps and plays significant ecological roles in their natural habitats. Owing to the considerable variability of the taxonomic [...] Read more.

The genus Neocaridina, originating from East Asia and representing a small-size landlocked shrimp group of the family Atyidae, is an important group of ornamental shrimps and plays significant ecological roles in their natural habitats. Owing to the considerable variability of the taxonomic characters it employed, Neocaridina is constantly under revision, and the validation of several species is currently questionable. In the present study, several Neocaridina shrimps were collected from the Baiyangdian drainage area. Through morphological examination, they exhibited delicately diagnostical differences in the dactyli of the third pereiopod and the endopod of the first and second pleopod and were classified into morph A, morph B and morph C. According to the literature description, morph A and morph C were identified as N. denticulata denticulata and N. denticulata sinensis, respectively. Among them, morph B presents an intermediate state between morph A and morph C. Subsequently, we determined the mitogenomes of morph A, morph B and morph C. Based on the morphological characteristics, genetic variation and phylogenetic tree, we contend that N. davidi, N. d. denticulata, N. d. sinensis and N. heteropoda should belong to the same species, and we propose retaining the name N. denticulata. The reconstructed mitogenomic phylogeny indicated that the monophyly of several genera within Atyidae has been challenged, suggesting that the established classification of Atyidae requires substantial taxonomic revision at all taxonomic levels. Furthermore, the tree’s topologies supported Atyidae at a deeper base within Caridea. More comprehensive taxon sampling is still needed to resolve the explicit internal relationships among Caridea. Full article

(This article belongs to the Special Issue Mitochondrial Genome 2024)

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19 pages, 2420 KiB

Open AccessArticle

The Adaptive Mechanism of Ginseng Rhizomes in Response to Habitat Changes

by Meng Zhang, Yingxin Sun, Zeliang Lv, Hongmei Lin, Mei Han and Limin Yang

Curr. Issues Mol. Biol. 2024, 46(11), 12260-12278; https://doi.org/10.3390/cimb46110728 (registering DOI) - 30 Oct 2024

Abstract

Panax ginseng, a perennial medicinal plant, utilizes its dried roots and rhizomes for medicinal purposes. Currently, in China, ginseng cultivation employs two methods: under-forest and farmland planting. These methods create distinct habitats, significantly influencing the ginseng’s rhizome morphology and, consequently, its economic [...] Read more.

Panax ginseng, a perennial medicinal plant, utilizes its dried roots and rhizomes for medicinal purposes. Currently, in China, ginseng cultivation employs two methods: under-forest and farmland planting. These methods create distinct habitats, significantly influencing the ginseng’s rhizome morphology and, consequently, its economic value. In this study, two-year-old ginsengs were transplanted into farmland (TCG), a larch forest (TLCG) and a Quercus mongolica forest (TQCG) to analyze the differences in rhizome phenotypes caused by habitat changes. The results showed that there were significant differences in light intensity and the soil’s available phosphorus and potassium contents between farmland and forest environments. The differences in habitats led to different adaptability of the ginseng’s rhizome morphology. Compared with TCG, the rhizomes of TLCG and TQCG were significantly elongated by 48.36% and 67.34%, respectively. After the rhizomes’ elongation in TLCG and TQCG, there was an increase in indole-3-acetic acid (IAA) contents and a decrease in lignin contents. By analyzing the expression of key genes, we found that, compared with TCG, the expression of key enzymes of lignin biosynthesis genes such as PgCOMT and PgCCR4 were down-regulated. The difference in ginseng’s rhizome length is related to the signal transduction pathway of auxin and gibberellin. In addition, we preliminarily screened out transcription factors PgWRKY75, PgDIV, and PgbHLH93.1, which can actively respond to habitat changes and play important roles in the elongation of ginseng rhizomes. In summary, this study elucidates the phenotypic plasticity strategy of ginseng rhizomes in response to habitat changes and delineates the regulatory mechanism behind phenotypic adaptation, offering novel insights into ginseng’s morphogenesis. Full article

(This article belongs to the Special Issue Molecular Mechanism of Plant Growth, Development and Secondary Metabolism)

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16 pages, 1940 KiB

Open AccessArticle

Preliminary Study on Lutetium-177 and Gold Nanoparticles: Apoptosis and Radiation Enhancement in Hepatic Cancer Cell Line

by Maria Anthi Kouri, Anastasios Georgopoulos, George E. Manios, Eirini Maratou, Aris Spathis, Sofia Chatziioannou, Kalliopi Platoni and Efstathios P. Efstathopoulos

Curr. Issues Mol. Biol. 2024, 46(11), 12244-12259; https://doi.org/10.3390/cimb46110727 (registering DOI) - 30 Oct 2024

Abstract

This study investigates a novel approach toward enhancing the efficacy of Lutetium-177 (Lu-177) radiopharmaceutical therapy by combining it with gold nanoparticles (AuNPs) in the HepG2 hepatic cancer cell line. Lu-177, known for its effective β radiation, also emits gamma rays at energies (113 [...] Read more.

This study investigates a novel approach toward enhancing the efficacy of Lutetium-177 (Lu-177) radiopharmaceutical therapy by combining it with gold nanoparticles (AuNPs) in the HepG2 hepatic cancer cell line. Lu-177, known for its effective β radiation, also emits gamma rays at energies (113 keV and 208 keV) near the photoelectric absorption range, suggesting potential for targeted and localized radiation enhancement when used in conjunction with AuNPs. Thus, HepG2 cells were treated at two different activity levels (74 MBq and 148 MBq), with Lu-177 alone, with a combination of Lu-177 and AuNPs in two sizes (10 nm and 50 nm), while some received no treatment. Treatment efficacy was assessed by quantifying the radiation enhancement ratio (RER) and the apoptosis levels. The results reveal that combining Lu-177 with AuNPs significantly increases cell death and apoptosis compared to Lu-177 alone, with 10 nm AuNPs demonstrating superior effectiveness. Additionally, varying Lu-177 activity levels influenced the treatment outcomes, with higher activity levels further augmenting the therapeutic impact of combined therapy. These findings underscore the potential of utilizing Lu-177’s beta, but also gamma, emissions, traditionally considered non-therapeutic, for localized radiation enhancement when combined with AuNPs. This novel strategy leverages Lu-177 as an internal irradiator to exploit gamma radiation for a targeted therapeutic advantage without requiring nanoparticle functionalization. The study provides a promising approach to improving radionuclide therapy and sets the stage for future research aimed at optimizing cancer treatments through the combined use of Lu-177 and AuNPs. Full article

(This article belongs to the Special Issue Molecular Insights into Radiation Oncology)

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14 pages, 1180 KiB

Open AccessArticle

Exploring Salivary Alpha-Amylase as a Biomarker in Periodontitis: A Comparative Analysis of Disease Stages and Clinical Correlations

by Nada Tawfig Hashim, Sadiah Fathima, Nurain Mohammad Hisham, Pooja Shivappa, Michael V. Magaogao, Md Sofiqul Islam, Sara Faisal Ahmed, Rasha Babiker and Muhammed Mustahsen Rahman

Curr. Issues Mol. Biol. 2024, 46(11), 12230-12243; https://doi.org/10.3390/cimb46110726 - 30 Oct 2024

Abstract

Periodontal disease, characterized by bacterial plaque accumulation and subsequent immune response, can lead to gingivitis and periodontitis if untreated. Salivary alpha-amylase (sAA) has emerged as a potential biomarker with implications in periodontal disease progression. Objectives: This study aimed to assess and compare salivary [...] Read more.

Periodontal disease, characterized by bacterial plaque accumulation and subsequent immune response, can lead to gingivitis and periodontitis if untreated. Salivary alpha-amylase (sAA) has emerged as a potential biomarker with implications in periodontal disease progression. Objectives: This study aimed to assess and compare salivary alpha-amylase levels in individuals with periodontitis and healthy controls and to investigate its relationship with clinical parameters of periodontal disease. Forty-five participants were categorized into periodontally healthy (n = 13), Stage I and II Periodontitis (n = 17), and Stage III and IV periodontitis (n = 15) groups. Saliva samples were collected and analyzed using ELISA kits. Statistical analyses included tests for normality, group comparisons, post hoc analysis, and correlation analysis. Significant differences in salivary alpha-amylase levels were observed among severity groups (p < 0.05), with higher levels in periodontitis patients than healthy controls. Spearman correlation revealed moderate positive associations between alpha-amylase levels and probing depth (PD) and clinical attachment loss (CAL). Elevated salivary alpha-amylase levels were found to be associated with more severe periodontal disease, suggesting its potential as a biomarker for periodontitis severity. These findings support the utility of salivary biomarkers in periodontal disease diagnosis and monitoring, although further validation and standardization are warranted for clinical application. Full article

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

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16 pages, 1976 KiB

Open AccessReview

Targeting PGK1: A New Frontier in Breast Cancer Therapy Under Hypoxic Conditions

by Jiayong Cui, Shengjun Chai, Rui Liu and Guoshuang Shen

Curr. Issues Mol. Biol. 2024, 46(11), 12214-12229; https://doi.org/10.3390/cimb46110725 - 30 Oct 2024

Abstract

Breast cancer represents one of the most prevalent malignant neoplasms affecting women, and its pathogenesis has garnered significant scholarly interest. Research indicates that the progression of breast cancer is intricately regulated by glucose metabolism. Under hypoxic conditions within the tumor microenvironment, breast cancer [...] Read more.

Breast cancer represents one of the most prevalent malignant neoplasms affecting women, and its pathogenesis has garnered significant scholarly interest. Research indicates that the progression of breast cancer is intricately regulated by glucose metabolism. Under hypoxic conditions within the tumor microenvironment, breast cancer cells generate ATP and essential biosynthetic precursors for growth via the glycolytic pathway. Notably, phosphoglycerate kinase 1 (PGK1) is intimately associated with the regulation of hypoxia-inducible factors in breast cancer and plays a crucial role in modulating glycolytic processes. Further investigation into the role of PGK1 in breast cancer pathogenesis is anticipated to identify novel therapeutic targets and strategies. This review consolidates current research on the regulation of glucose metabolism and the function of PGK1 in breast cancer within hypoxic conditions. It aims to offer a significant theoretical foundation for elucidating the mechanisms underlying breast cancer progression and metastasis, thereby facilitating the development of innovative treatment approaches. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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18 pages, 2289 KiB

Open AccessReview

Microbial Dynamics in Periodontal Regeneration: Understanding Microbiome Shifts and the Role of Antifouling and Bactericidal Materials: A Narrative Review

by Nada Tawfig Hashim, Rasha Babiker, Sivan Padma Priya, Riham Mohammed, Nallan CSK Chaitanya, Vivek Padmanabhan, Shadi El Bahra, Muhammed Mustahsen Rahman and Bakri Gobara Gismalla

Curr. Issues Mol. Biol. 2024, 46(11), 12196-12213; https://doi.org/10.3390/cimb46110724 - 30 Oct 2024

Abstract

Periodontal regeneration is a multifaceted therapeutic approach to restore the tooth-supporting structures lost due to periodontal diseases. This manuscript explores the intricate interactions between regenerative therapies and the oral microbiome, emphasizing the critical role of microbial balance in achieving long-term success. While guided [...] Read more.

Periodontal regeneration is a multifaceted therapeutic approach to restore the tooth-supporting structures lost due to periodontal diseases. This manuscript explores the intricate interactions between regenerative therapies and the oral microbiome, emphasizing the critical role of microbial balance in achieving long-term success. While guided tissue regeneration (GTR), bone grafting, and soft tissue grafting offer promising outcomes in terms of tissue regeneration, these procedures can inadvertently alter the oral microbial ecosystem, potentially leading to dysbiosis or pathogenic recolonization. Different grafting materials, including autografts, allografts, xenografts, and alloplasts, influence microbial shifts, with variations in the healing timeline and microbial stabilization. Biologics and antimicrobials, such as enamel matrix derivatives (EMD) and sub-antimicrobial dose doxycycline (SDD), play a key role in promoting microbial homeostasis by supporting tissue repair and reducing pathogenic bacteria. Emerging strategies, such as enzyme-based therapies and antifouling materials, aim to disrupt biofilm formation and enhance the effectiveness of periodontal treatments. Understanding these microbial dynamics is essential for optimizing regenerative therapies and improving patient outcomes. The future of periodontal therapy lies in the development of advanced materials and strategies that not only restore lost tissues but also stabilize the oral microbiome, ultimately leading to long-term periodontal health. Full article

(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences — Focusing on Medicine, Biomaterials and Tissue Engineering Fields)

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Graphical abstract

13 pages, 3255 KiB

Open AccessArticle

Switch/Sucrose Non-Fermentable (SWI/SNF) Complex—Partial Loss in Sinonasal Squamous Cell Carcinoma: A High-Grade Morphology Impact and Progression

by Roberto Onner Cruz-Tapia, Ana María Cano-Valdez, Abelardo Meneses-García, Lorena Correa-Arzate, Adriana Molotla-Fragoso, Guillermo Villagómez-Olea, Diana Brisa Sevilla-Lizcano and Javier Portilla-Robertson

Curr. Issues Mol. Biol. 2024, 46(11), 12183-12195; https://doi.org/10.3390/cimb46110723 - 30 Oct 2024

Abstract

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with an unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are the current targets for diagnosis and treatment. The most [...] Read more.

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with an unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are the current targets for diagnosis and treatment. The most common type of cancer originating in the sinonasal tract is sinonasal squamous cell carcinomas (SNSCCs), which present different histological patterns and variable histological aggressiveness. A significant number of alterations have been reported in sinonasal tumors, including deficiencies in the Switch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex. In the sinonasal tract, deficiencies of the subunits SMARCB1/INI1, SMARCA4/BRG1, and SMARCA2 have been noted in carcinomas, adenocarcinomas, and soft tissue tumors with a distinctive high-grade morphology and a fatal prognosis. Objective: The objective of this study is to identify the status of the SWI/SNF complex using immunohistochemistry in sinonasal squamous cell carcinomas and their association with morphology and survival. Methods: A total of 103 sinonasal carcinomas with different grades of squamous differentiation were analyzed; the selection was based on those cases with high-grade morphology. The carcinomas were then evaluated immunohistochemically for SMARCB1 and SMARCA4 proteins. Their expression was compared with the biological behavior and survival of the patients. Results: Among the SNSCCs, 47% corresponded to the non-keratinizing squamous cell carcinoma (NKSCC) type with high-grade characteristics, 40% were keratinizing squamous cell carcinomas (KSCCs), 9% were SMARCB1-deficient carcinomas, and 4% were SMARCA4-deficient carcinomas. Mosaic expression for SMARCB1 (NKSCC—33%; KSCC—21.9%) and SMARCA4 (NKSCC—14.6%; KSCC—12.2%) was identified, showing an impact on tumor size and progression. Conclusions: We identified that that the partial loss (mosaic expression) of SMARCB1 in SNSCCs is associated with high-grade malignant characteristics and a negative effect on patient survival; meanwhile, SMARCA4-mosaic expression in SNSCCs is associated with high-grade malignant characteristics and an increase in tumor size concerning the intact SMARCA4. Full article

(This article belongs to the Special Issue Adhesion, Metastasis and Inhibition of Cancer Cells, 2nd Edition)

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