Current Issues in Molecular Biology

15 pages, 2102 KiB

Open AccessArticle

Intranasal Insulin Eases Autism in Rats via GDF-15 and Anti-Inflammatory Pathways

by Duygu Burcu Arda, Kerem Can Tunç, Mehmet Fatih Bozkurt, Ejder Saylav Bora, Ayşe Çiğel and Oytun Erbaş

Curr. Issues Mol. Biol. 2024, 46(9), 10530-10544; https://doi.org/10.3390/cimb46090624 (registering DOI) - 20 Sep 2024

Abstract

In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing [...] Read more.

In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing various proteins, modulating anti-inflammatory pathways in the brain, and reducing signaling molecules such as interleukins. This study seeks to explore the potential therapeutic benefits of IN insulin in a rat model of autism induced by PPA. Thirty male Wistar albino rats were categorized into three cohorts: the control group, the PPA-induced autism (250 mg/kg/day intraperitoneal PPA dosage for five days) group, treated with saline via IN, and the PPA-induced autism group, treated with 25 U/kg/day (250 µL/kg/day) insulin via IN. All treatments were administered for 15 days. After behavioral testing, all animals were euthanized, and brain tissue and blood samples were collected for histopathological and biochemical assessments. Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests conducted on the rats. Moreover, insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels within autism models. Additionally, there is a notable elevation in the brain nerve growth factor level (p < 0.05) and GDF-15 (p < 0.05). The assessment of cell counts within the hippocampal region and cerebellum revealed that insulin displayed effects in decreasing glial cells and inducing a significant augmentation in cell types such as the Purkinje and Pyramidal cells. The administration of insulin via IN exhibits alleviating effects on autism-like behavioral, biochemical, and histopathological alterations induced by PPA in rats. Insulin-dependent protective effects show anti-inflammatory, anti-oxidative, and neuroprotective roles of insulin admitted nasally. Full article

(This article belongs to the Topic Autism: Molecular Bases, Diagnosis and Therapies, 2nd Volume)

► Show Figures

Figure 1

38 pages, 7020 KiB

Open AccessArticle

Antidiabetic and Antihyperlipidemic Activities and Molecular Mechanisms of Phyllanthus emblica L. Extract in Mice on a High-Fat Diet

by Hsing-Yi Lin, Cheng-Hsiu Lin, Yueh-Hsiung Kuo and Chun-Ching Shih

Curr. Issues Mol. Biol. 2024, 46(9), 10492-10529; https://doi.org/10.3390/cimb46090623 (registering DOI) - 20 Sep 2024

Abstract

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by [...] Read more.

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1_C, and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3β (GSK3β) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice. Full article

(This article belongs to the Section Molecular Pharmacology)

► Show Figures

Figure 1

30 pages, 2595 KiB

Open AccessReview

Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family

by Anastasiia T. Davletgildeeva and Nikita A. Kuznetsov

Curr. Issues Mol. Biol. 2024, 46(9), 10462-10491; https://doi.org/10.3390/cimb46090622 (registering DOI) - 20 Sep 2024

Abstract

Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and [...] Read more.

Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of Escherichia coli AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1–8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants. Full article

(This article belongs to the Special Issue DNA Damage and Repair in Health and Diseases)

► Show Figures

Figure 1

18 pages, 3031 KiB

Open AccessReview

Hyaluronic Acid in Nanopharmaceuticals: An Overview

by Sina Matalqah, Zainab Lafi and Sara Yousef Asha

Curr. Issues Mol. Biol. 2024, 46(9), 10444-10461; https://doi.org/10.3390/cimb46090621 - 20 Sep 2024

Abstract

Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability [...] Read more.

Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability to interact with various therapeutic agents, improving the delivery and efficacy of drugs. HA-based nanoparticles, including solid lipid nanoparticles, and polymeric nanogels, offer controlled release, enhanced stability, and targeted delivery of therapeutic agents. These innovations significantly improve therapeutic outcomes and reduce side effects, making HA an essential tool in modern medicine. In general, HA-modified liposomes enhance drug encapsulation and targeting, while HA-modified solid lipid nanoparticles (SLNs) provide a solid lipid core for drug encapsulation, offering controlled release and stability. This article provides an overview of the potential applications and recent advancements of HA in nanopharmaceuticals, emphasizing its significant impact on the evolving field of targeted drug delivery and advanced therapeutic strategies. By delving into the unique properties of HA and its compatibility with various therapeutic agents, this review underscores the promising potential of HA in revolutionizing nanopharmaceuticals. Full article

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

► Show Figures

Graphical abstract

14 pages, 1314 KiB

Open AccessArticle

RNA Sequencing of Sperm from Healthy Cattle and Horses Reveals the Presence of a Large Bacterial Population

by Paula Navarrete-López, Victoria Asselstine, María Maroto, Marta Lombó, Ángela Cánovas and Alfonso Gutiérrez-Adán

Curr. Issues Mol. Biol. 2024, 46(9), 10430-10443; https://doi.org/10.3390/cimb46090620 - 19 Sep 2024

Abstract

RNA molecules within ejaculated sperm can be characterized through whole-transcriptome sequencing, enabling the identification of pivotal transcripts that may influence reproductive success. However, the profiling of sperm transcriptomes through next-generation sequencing has several limitations impairing the identification of functional transcripts. In this study, [...] Read more.

RNA molecules within ejaculated sperm can be characterized through whole-transcriptome sequencing, enabling the identification of pivotal transcripts that may influence reproductive success. However, the profiling of sperm transcriptomes through next-generation sequencing has several limitations impairing the identification of functional transcripts. In this study, we explored the nature of the RNA sequences present in the sperm transcriptome of two livestock species, cattle and horses, using RNA sequencing (RNA-seq) technology. Through processing of transcriptomic data derived from bovine and equine sperm cell preparations, low mapping rates to the reference genomes were observed, mainly attributed to the presence of ribosomal RNA and bacteria in sperm samples, which led to a reduced sequencing depth of RNAs of interest. To explore the presence of bacteria, we aligned the unmapped reads to a complete database of bacterial genomes and identified bacteria-associated transcripts which were characterized. This analysis examines the limitations associated with sperm transcriptome profiling by reporting the nature of the RNA sequences among which bacterial RNA was found. These findings can aid researchers in understanding spermatozoal RNA-seq data and pave the way for the identification of molecular markers of sperm performance. 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)

► Show Figures

Figure 1

19 pages, 2523 KiB

Open AccessArticle

Integrative Analyses of Mitophagy-Related Genes and Mechanisms Associated with Type 2 Diabetes in Muscle Tissue

by Wangjia Mao, Guannan Zong, Yuan Gao, Shen Qu and Xiaoyun Cheng

Curr. Issues Mol. Biol. 2024, 46(9), 10411-10429; https://doi.org/10.3390/cimb46090619 - 18 Sep 2024

Abstract

Type 2 diabetes (T2D) represents the most prevalent metabolic condition that is primarily distinguished by a range of metabolic imbalances, including hyperglycemia, hyperlipidemia, and insulin resistance (IR). Currently, mitophagy has become increasingly recognized as an important process involved in the pathogenesis and progression [...] Read more.

Type 2 diabetes (T2D) represents the most prevalent metabolic condition that is primarily distinguished by a range of metabolic imbalances, including hyperglycemia, hyperlipidemia, and insulin resistance (IR). Currently, mitophagy has become increasingly recognized as an important process involved in the pathogenesis and progression of T2D. Therefore, it is very important to explore the role of mitochondrial damage and autophagy-related genes in T2D. This study investigated the role of mitophagy in the development of T2D, and 12 MRHGs associated with T2D were identified using bioinformatic analysis and machine learning methods. Our findings provide the first insight into mitophagy-related genes and their mechanisms in T2D. This study aimed to investigate possible molecular targets for therapy and the underlying mechanisms involved in T2D. This information might be useful to further elucidate the pathogenesis of T2D-related diseases and identify more optimal therapeutic approaches. Full article

(This article belongs to the Collection Molecular Mechanisms in Human Diseases)

► Show Figures

Figure 1

15 pages, 938 KiB

Open AccessReview

A New Frontier in Cystic Fibrosis Pathophysiology: How and When Clock Genes Can Affect the Inflammatory/Immune Response in a Genetic Disease Model

by Annalucia Carbone, Pamela Vitullo, Sante Di Gioia, Stefano Castellani and Massimo Conese

Curr. Issues Mol. Biol. 2024, 46(9), 10396-10410; https://doi.org/10.3390/cimb46090618 - 18 Sep 2024

Abstract

Cystic fibrosis (CF) is a monogenic syndrome caused by variants in the CF Transmembrane Conductance Regulator (CFTR) gene, affecting various organ and systems, in particular the lung, pancreas, sweat glands, liver, gastrointestinal tract, vas deferens, and vascular system. While for some [...] Read more.

Cystic fibrosis (CF) is a monogenic syndrome caused by variants in the CF Transmembrane Conductance Regulator (CFTR) gene, affecting various organ and systems, in particular the lung, pancreas, sweat glands, liver, gastrointestinal tract, vas deferens, and vascular system. While for some organs, e.g., the pancreas, a strict genotype-phenotype occurs, others, such as the lung, display a different pathophysiologic outcome in the presence of the same mutational asset, arguing for genetic and environmental modifiers influencing severity and clinical trajectory. CFTR variants trigger a pathophysiological cascade of events responsible for chronic inflammatory responses, many aspects of which, especially related to immunity, are not ascertained yet. Although clock genes expression and function are known modulators of the innate and adaptive immunity, their involvement in CF has been only observed in relation to sleep abnormalities. The aim of this review is to present current evidence on the clock genes role in immune-inflammatory responses at the lung level. While information on this topic is known in other chronic airway diseases (chronic obstructive pulmonary disease and asthma), CF lung disease (CFLD) is lacking in this knowledge. We will present the bidirectional effect between clock genes and inflammatory factors that could possibly be implicated in the CFLD. It must be stressed that besides sleep disturbance and its mechanisms, there are not studies directly addressing the exact nature of clock genes’ involvement in inflammation and immunity in CF, pointing out the directions of new and deepened studies in this monogenic affection. Importantly, clock genes have been found to be druggable by means of genetic tools or pharmacological agents, and this could have therapeutic implications in CFLD. Full article

(This article belongs to the Special Issue Complex Molecular Mechanism of Monogenic Diseases: 3rd Edition)

► Show Figures

Figure 1

27 pages, 2003 KiB

Open AccessReview

Analysis of Beyfortus^® (Nirsevimab) Immunization Campaign: Effectiveness, Biases, and ADE Risks in RSV Prevention

by Hélène Banoun

Curr. Issues Mol. Biol. 2024, 46(9), 10369-10395; https://doi.org/10.3390/cimb46090617 - 18 Sep 2024

Abstract

Respiratory infections with respiratory syncytial virus (RSV) account for an important part of hospital admissions for acute respiratory infections. Nirsevimab has been developed to reduce the hospital burden of RSV infections. Compared with the product previously used, it has a stronger binding capacity [...] Read more.

Respiratory infections with respiratory syncytial virus (RSV) account for an important part of hospital admissions for acute respiratory infections. Nirsevimab has been developed to reduce the hospital burden of RSV infections. Compared with the product previously used, it has a stronger binding capacity to RSV F protein and a high affinity for FcRn (neonatal receptor for the Fc fragment of IgG), which extends its lifespan. Nirsevimab has been shown to be highly effective in reducing hospitalization rates of RSV infections but a large or unknown number of treated subjects have been excluded in clinical and post-marketing studies. However, analysis of these studies cannot exclude that, in rare cases, nirsevimab facilitates and worsens RSV infection (or other respiratory infections). This could be attributable to antibody-dependent enhancement (ADE) which has been observed with RSV F protein antibodies in inactivated vaccine trials. This risk has been incompletely assessed in pre-clinical and clinical trials (incomplete exploration of nirsevimab effector functions and pharmacokinetics). ADE by disruption of the immune system (not studied and due to FcRn binding) could explain why there is no reduction in all-cause hospital admissions in treated age groups. Given the high price of nirsevimab, the cost-effectiveness of mass immunization campaigns may therefore be debated from an economic as well as a scientific point of view. Full article

(This article belongs to the Section Molecular Medicine)

► Show Figures

Figure 1

18 pages, 4458 KiB

Open AccessArticle

Genetics and Traumatic Brain Injury: Findings from an Exome-Based Study of a 50-Patient Case Series

by Alesya S. Gracheva, Darya A. Kashatnikova, Ivan V. Redkin, Vladislav E. Zakharchenko, Artem N. Kuzovlev and Lyubov E. Salnikova

Curr. Issues Mol. Biol. 2024, 46(9), 10351-10368; https://doi.org/10.3390/cimb46090616 - 17 Sep 2024

Abstract

Traumatic brain injury (TBI) is the leading cause of global mortality and morbidity. Because TBI is accident-related, the role of genetics in predisposing to TBI has been largely unexplored. However, the likelihood of injury may not be entirely random and may be associated [...] Read more.

Traumatic brain injury (TBI) is the leading cause of global mortality and morbidity. Because TBI is accident-related, the role of genetics in predisposing to TBI has been largely unexplored. However, the likelihood of injury may not be entirely random and may be associated with certain physical and mental characteristics. In this study, we analyzed the exomes of 50 patients undergoing rehabilitation after TBI. Patients were divided into three groups according to rehabilitation outcome: improvement, no change, and deterioration/death. We focused on rare, potentially functional missense and high-impact variants in genes intolerant to these variants. The concordant results from the three independent groups of patients allowed for the suggestion of the existence of a genetic predisposition to TBI, associated with rare functional variations in intolerant genes, with a prevalent dominant mode of inheritance and neurological manifestations in the genetic phenotypes according to the OMIM database. Forty-four of the 50 patients had one or more rare, potentially deleterious variants in one or more neurological genes. Comparison of these results with those of a 50-sampled matched non-TBI cohort revealed significant differences: P = 2.2 × 10⁻⁶, OR = 4.89 (1.77–13.47). There were no differences in the distribution of the genes of interest between the TBI patient groups. Our exploratory study provides new insights into the impact of genetics on TBI risk and is the first to address potential genetic susceptibility to TBI. Full article

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

► Show Figures

Figure 1

16 pages, 6210 KiB

Open AccessArticle

Transcriptomic and Metabolic Analysis Reveals Genes and Pathways Associated with Flesh Pigmentation in Potato (Solanum tuberosum) Tubers

by Man Li, Yuting Xiong, Xueying Yang, Yuliang Gao and Kuihua Li

Curr. Issues Mol. Biol. 2024, 46(9), 10335-10350; https://doi.org/10.3390/cimb46090615 - 17 Sep 2024

Abstract

Anthocyanins, flavonoid pigments, are responsible for the purple and red hues in potato tubers. This study analyzed tubers from four potato cultivars—red RR, purple HJG, yellow QS9, and white JZS8—to elucidate the genetic mechanisms underlying tuber pigmentation. Our transcriptomic analysis identified over 2400 [...] Read more.

Anthocyanins, flavonoid pigments, are responsible for the purple and red hues in potato tubers. This study analyzed tubers from four potato cultivars—red RR, purple HJG, yellow QS9, and white JZS8—to elucidate the genetic mechanisms underlying tuber pigmentation. Our transcriptomic analysis identified over 2400 differentially expressed genes between these varieties. Notably, genes within the flavonoid biosynthesis pathway were enriched in HJG and RR compared to the non-pigmented JZS8, correlating with their higher levels of anthocyanin precursors and related substances. Hierarchical clustering revealed inverse expression patterns for the key genes involved in anthocyanin metabolism between pigmented and non-pigmented varieties. Among these, several MYB transcription factors displayed strong co-expression with anthocyanin biosynthetic genes, suggesting a regulatory role. Specifically, the expression of 16 MYB genes was validated using qRT-PCR to be markedly higher in pigmented HJG and RR versus JZS8, suggesting that these MYB genes might be involved in tuber pigmentation. This study comprehensively analyzed the transcriptome of diverse potato cultivars, highlighting specific genes and metabolic pathways involved in tuber pigmentation. These findings provide potential molecular targets for breeding programs focused on enhancing tuber color. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding)

► Show Figures

Figure 1

23 pages, 11085 KiB

Open AccessArticle

Exopolysaccharides from the Green Microalga Strain Coelastrella sp. BGV—Isolation, Characterization, and Assessment of Anticancer Potential

by Tanya Toshkova-Yotova, Inna Sulikovska, Vera Djeliova, Zdravka Petrova, Manol Ognyanov, Petko Denev, Reneta Toshkova and Ani Georgieva

Curr. Issues Mol. Biol. 2024, 46(9), 10312-10334; https://doi.org/10.3390/cimb46090614 - 16 Sep 2024

Abstract

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a [...] Read more.

Algal metabolites have been extensively studied as potential anticancer therapeutics. Among them, polysaccharides have attracted much attention because of their beneficial biological effects and safety. In the present research, the chemical characteristics, antitumor, and proapoptotic activities of extracellular polysaccharides (EPS) isolated from a new Bulgarian strain of the green microalga Coelastrella sp. BGV were investigated. A fast and convenient method of precipitation with cold ethanol was used to isolate EPS from the culture medium. The chemical characteristics of the isolated EPS were examined by colorimetric and spectrophotometric analyses, HPSEC-RID and HPLC-UV chromatography, and FT-IR spectroscopy. The results showed that the isolated EPS sample consists of three carbohydrate fractions with different molecular weights (11.5 × 10⁴ Da, 30.7 × 10⁴ Da, and 72.4 × 10⁴ Da, respectively) and contains 7.14 (w/w%) protein. HPLC-UV analysis revealed the presence of galactose and fucose. The total uronic acid content in the sample was 4.5 (w/w%). The IR-FT spectrum of EPS revealed the presence of various functional groups typical of a polysaccharide (or proteoglycan) composed primarily of neutral sugars. The anticancer potential of the obtained EPS was assessed using cell lines with cancerous and non-cancerous origins as in vitro experimental models. The results of the performed MTT assay showed that EPS reduced the viability of the cervical and mammary carcinoma cell lines HeLa and MCF-7, while the control non-cancer cell lines BALB/3T3 and HaCaT were less affected. The HeLa cell line showed the highest sensitivity to the effects of EPS and was therefore used for further studies of its anticancer potential. The ability of EPS to inhibit cancer cell migration was demonstrated by wound-healing (scratch) assay. The cell cycle FACS analysis indicated that the EPS treatment induced significant increases in the sub G1 cell population and decreases of the percentages of cells in the G1, S, and G2-M phases, compared to the control. The fluorescent microscopy studies performed using three different staining methods in combination with Annexin V-FITC flow cytometric analysis clearly demonstrate the ability of EPS to induce cancer cell death via the apoptosis pathway. Moreover, an altered pattern and intensity of the immunocytochemical staining for the apoptosis- and proliferation-related proteins p53, bcl2, and Ki67 was detected in EPS-treated HeLa cancer cells as compared to the untreated controls. The obtained results characterize the new local strain of green microalgae Coelastrella sp. BGV as a producer of EPS with selective antitumor activity and provide an opportunity for further studies of its pharmacological and biotechnological potential. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

► Show Figures

Figure 1

13 pages, 751 KiB

Open AccessReview

Research Progress on Photoperiod Gene Regulation of Heading Date in Rice

by Jian Song, Liqun Tang, Yongtao Cui, Honghuan Fan, Xueqiang Zhen and Jianjun Wang

Curr. Issues Mol. Biol. 2024, 46(9), 10299-10311; https://doi.org/10.3390/cimb46090613 - 16 Sep 2024

Abstract

Heading date is a critical physiological process in rice that is influenced by both genetic and environmental factors. The photoperiodic pathway is a primary regulatory mechanism for rice heading, with key florigen genes Hd3a (Heading date 3a) and RFT1 (RICE FLOWERING LOCUS T1) [...] Read more.

Heading date is a critical physiological process in rice that is influenced by both genetic and environmental factors. The photoperiodic pathway is a primary regulatory mechanism for rice heading, with key florigen genes Hd3a (Heading date 3a) and RFT1 (RICE FLOWERING LOCUS T1) playing central roles. Upstream regulatory pathways, including Hd1 and Ehd1, also significantly impact this process. This review aims to provide a comprehensive examination of the localization, cloning, and functional roles of photoperiodic pathway-related genes in rice, and to explore the interactions among these genes as well as their pleiotropic effects on heading date. We systematically review recent advancements in the identification and functional analysis of genes involved in the photoperiodic pathway. We also discuss the molecular mechanisms underlying rice heading date variation and highlight the intricate interactions between key regulatory genes. Significant progress has been made in understanding the molecular mechanisms of heading date regulation through the cloning and functional analysis of photoperiod-regulating genes. However, the regulation of heading date remains complex, and many underlying mechanisms are not yet fully elucidated. This review consolidates current knowledge on the photoperiodic regulation of heading date in rice, emphasizing novel findings and gaps in the research. It highlights the need for further exploration of the interactions among flowering-related genes and their response to environmental signals. Despite advances, the full regulatory network of heading date remains unclear. Further research is needed to elucidate the intricate gene interactions, transcriptional and post-transcriptional regulatory mechanisms, and the role of epigenetic factors such as histone methylation in flowering time regulation. This review provides a detailed overview of the current understanding of photoperiodic pathway genes in rice, setting the stage for future research to address existing gaps and improve our knowledge of rice flowering regulation. Full article

(This article belongs to the Special Issue Advances in Multi-Omics for Functional Genomics Studies and Molecular Breeding)

► Show Figures

Figure 1

35 pages, 3888 KiB

Open AccessReview

Gene Expression Regulation and the Signal Transduction of Programmed Cell Death

by Saqirile, Yuxin Deng, Kexin Li, Wenxin Yan, Ke Li and Changshan Wang

Curr. Issues Mol. Biol. 2024, 46(9), 10264-10298; https://doi.org/10.3390/cimb46090612 - 16 Sep 2024

Abstract

Cell death is of great significance in maintaining tissue homeostasis and bodily functions. With considerable research coming to the fore, it has been found that programmed cell death presents in multiple modalities in the body, which is not only limited to apoptosis, but [...] Read more.

Cell death is of great significance in maintaining tissue homeostasis and bodily functions. With considerable research coming to the fore, it has been found that programmed cell death presents in multiple modalities in the body, which is not only limited to apoptosis, but also can be divided into autophagy, pyroptosis, ferroptosis, mitotic catastrophe, entosis, netosis, and other ways. Different forms of programmed cell death have disparate or analogous characteristics with each other, and their occurrence is accompanied by multiple signal transduction and the role of a myriad of regulatory factors. In recent years, scholars across the world have carried out considerable in-depth research on programmed cell death, and new forms of cell death are being discovered continually. Concomitantly, the mechanisms of intricate signaling pathways and regulators have been discovered. More critically, cancer cells tend to choose distinct ways to evade cell death, and different tumors adapt to different manners of death. Therefore, targeting the cell death network has been regarded as an effective tumor treatment strategy for a long time. The objective of our paper is to review the signaling pathways and gene regulation in several typical types of programmed cell death and their correlation with cancer. Full article

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

► Show Figures

Figure 1

5 pages, 947 KiB

Open AccessEditorial

Current Landscape of Chronic Inflammatory Dermatoses: Where We Are and Where We Are Heading

by Aleksandra Sójka and Piotr K. Krajewski

Curr. Issues Mol. Biol. 2024, 46(9), 10259-10263; https://doi.org/10.3390/cimb46090611 - 16 Sep 2024

Abstract

Chronic inflammatory dermatoses represent a heterogeneous group of skin disorders that are often characterized by persistent and relapsing inflammation, with complex underlying pathomechanisms [...] Full article

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

► Show Figures

Figure 1

10 pages, 11741 KiB

Open AccessArticle

mRNA Fragmentation Pattern Detected by SHAPE

by Shanshan Feng, Ting Chen, Yunlong Zhang and Changrui Lu

Curr. Issues Mol. Biol. 2024, 46(9), 10249-10258; https://doi.org/10.3390/cimb46090610 - 16 Sep 2024

Abstract

The success of messenger RNA (mRNA) vaccines in controlling COVID-19 has warranted further developments in new technology. Currently, their quality control process largely relies on low-resolution electrophoresis for detecting chain breaks. Here, we present an approach using multi-primer reverse transcription sequencing (MPRT-seq) to [...] Read more.

The success of messenger RNA (mRNA) vaccines in controlling COVID-19 has warranted further developments in new technology. Currently, their quality control process largely relies on low-resolution electrophoresis for detecting chain breaks. Here, we present an approach using multi-primer reverse transcription sequencing (MPRT-seq) to identify degradation fragments in mRNA products. Using this in-house-made mRNA containing two antigens and untranslated regions (UTRs), we analyzed the mRNA completeness and degradation pattern at a nucleotide resolution. We then analyzed the sensitive base sequence and its correlation with the secondary structure. Our MPRT-seq mapping shows that certain sequences on the 5′ of bulge–stem–loop structures can result in preferential chain breaks. Our results agree with commonly used capillary electrophoresis (CE) integrity analysis but at a much higher resolution, and can improve mRNA stability by providing information to remove sensitive structures or sequences in the mRNA sequence design. Full article

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

► Show Figures

Figure 1

31 pages, 5879 KiB

Open AccessArticle

Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue

by Błażej Ochman, Piotr Limanówka, Sylwia Mielcarska, Agnieszka Kula, Miriam Dawidowicz, Wiktor Wagner, Dorota Hudy, Monika Szrot, Jerzy Zbigniew Piecuch, Jerzy Piecuch, Zenon Czuba and Elżbieta Świętochowska

Curr. Issues Mol. Biol. 2024, 46(9), 10218-10248; https://doi.org/10.3390/cimb46090609 - 15 Sep 2024

Abstract

Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate the expression of SEMA7A, SEMA4D, ADAM8, and ADAMTS10 in colorectal cancer (CRC) in relation to [...] Read more.

Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate the expression of SEMA7A, SEMA4D, ADAM8, and ADAMTS10 in colorectal cancer (CRC) in relation to the mutational landscape of KRAS, NRAS, BRAF, PIK3CA, and AKT genes, microsatellite instability (MSI) status, and clinicopathological features. We also examined the associations between the expression of these proteins and selected cytokines, chemokines, and growth factors, assessed using a multiplex assay. Protein concentrations were quantified using ELISA in CRC tumors and tumor-free surgical margin tissue homogenates. Gene mutations were evaluated via RT-PCR, and MSI status was determined using immunohistochemistry (IHC). GSEA and statistical analyses were performed using R Studio. We observed a significantly elevated expression of SEMA7A in BRAF-mutant CRC tumors and an overexpression of ADAM8 in KRAS 12/13-mutant tumors. The expression of ADAMTS10 was decreased in PIK3CA-mutant CRC tumors. No significant differences in the expression of the examined proteins were observed based on MSI status. The SEMA7A and SEMA4D expressions were correlated with the expression of numerous cytokines associated with various immune processes. The potential immunomodulatory functions of these molecules and their suitability as therapeutic targets require further investigation. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers, 2nd Edition)

► Show Figures

Figure 1

18 pages, 1822 KiB

Open AccessReview

Biochemical Pathways Delivering Distinct Glycosphingolipid Patterns in MDA-MB-231 and MCF-7 Breast Cancer Cells

by Anita Markotić, Jasminka Omerović, Sandra Marijan, Nikolina Režić-Mužinić and Vedrana Čikeš Čulić

Curr. Issues Mol. Biol. 2024, 46(9), 10200-10217; https://doi.org/10.3390/cimb46090608 - 15 Sep 2024

Abstract

The complex structure of glycosphingolipids (GSLs) supports their important role in cell function as modulators of growth factor receptors and glutamine transporters in plasma membranes. The aberrant composition of clustered GSLs within signaling platforms, so-called lipid rafts, inevitably leads to tumorigenesis due to [...] Read more.

The complex structure of glycosphingolipids (GSLs) supports their important role in cell function as modulators of growth factor receptors and glutamine transporters in plasma membranes. The aberrant composition of clustered GSLs within signaling platforms, so-called lipid rafts, inevitably leads to tumorigenesis due to disturbed growth factor signal transduction and excessive uptake of glutamine and other molecules needed for increased energy and structural molecule cell supply. GSLs are also involved in plasma membrane processes such as cell adhesion, and their transition converts cells from epithelial to mesenchymal with features required for cell migration and metastasis. Glutamine activates the mechanistic target of rapamycin complex 1 (mTORC1), resulting in nucleotide synthesis and proliferation. In addition, glutamine contributes to the cancer stem cell GD2 ganglioside-positive phenotype in the triple-negative breast cancer cell line MDA-MB-231. Thieno[2,3-b]pyridine derivative possesses higher cytotoxicity against MDA-MB-231 than against MCF-7 cells and induces a shift to aerobic metabolism and a decrease in S(6)nLc4Cer GSL-positive cancer stem cells in the MDA-MB-231 cell line. In this review, we discuss findings in MDA-MB-231, MCF-7, and other breast cancer cell lines concerning their differences in growth factor receptors and recent knowledge of the main biochemical pathways delivering distinct glycosphingolipid patterns during tumorigenesis and therapy. Full article

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

► Show Figures

Figure 1

20 pages, 833 KiB

Open AccessReview

The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders

by Alessandro Galgani, Marco Scotto and Filippo S. Giorgi

Curr. Issues Mol. Biol. 2024, 46(9), 10180-10199; https://doi.org/10.3390/cimb46090607 - 14 Sep 2024

Abstract

Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that are markedly and precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson’s and Alzheimer’s diseases. In humans, although many tools have been developed to infer information on these nuclei, [...] Read more.

Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that are markedly and precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson’s and Alzheimer’s diseases. In humans, although many tools have been developed to infer information on these nuclei, encompassing neuroimaging and neurophysiological methods, a detailed and specific direct evaluation of their cellular features in vivo has been difficult to obtain until recent years. The development of induced pluripotent stem cell (iPSC) models has allowed research to deeply delve into the cellular and molecular biology of NSS neurons. In fact, iPSCs can be produced easily and non-invasively from patients’ fibroblasts or circulating blood monocytes, by de-differentiating those cells using specific protocols, and then be re-differentiated towards neural phenotypes, which may reproduce the specific features of the correspondent brain neurons (including NSS ones) from the same patient. In this review, we summarized findings obtained in the field of NDDs using iPSCs, with the aim to understand how reliably these might represent in vitro models of NSS. We found that most of the current literature in the field of iPSCs and NSSs in NDDs has focused on midbrain dopaminergic neurons in Parkinson’s disease, providing interesting results on cellular pathophysiology and even leading to the first human autologous transplantation. Differentiation protocols for noradrenergic, cholinergic, and serotoninergic neurons have also been recently defined and published. Thus, it might be expected that in the near future, this approach could extend to other NSSs and other NDDs. Full article

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

► Show Figures

Figure 1

20 pages, 10282 KiB

Open AccessArticle

Molecular Integrative Study on Inhibitory Effects of Pentapeptides on Polymerization and Cell Toxicity of Amyloid-β Peptide (1–42)

by Lianmeng Ye, Nuela Manka’a Che Ajuyo, Zhongyun Wu, Nan Yuan, Zhengpan Xiao, Wenyu Gu, Jiazheng Zhao, Yechun Pei, Yi Min and Dayong Wang

Curr. Issues Mol. Biol. 2024, 46(9), 10160-10179; https://doi.org/10.3390/cimb46090606 - 14 Sep 2024

Abstract

Alzheimer’s Disease (AD) is a multifaceted neurodegenerative disease predominantly defined by the extracellular accumulation of amyloid-β (Aβ) peptide. In light of this, in the past decade, several clinical approaches have been used aiming at developing peptides for therapeutic use in AD. The use [...] Read more.

Alzheimer’s Disease (AD) is a multifaceted neurodegenerative disease predominantly defined by the extracellular accumulation of amyloid-β (Aβ) peptide. In light of this, in the past decade, several clinical approaches have been used aiming at developing peptides for therapeutic use in AD. The use of cationic arginine-rich peptides (CARPs) in targeting protein aggregations has been on the rise. Also, the process of peptide development employing computational approaches has attracted a lot of attention recently. Using a structure database containing pentapeptides made from 20 L-α amino acids, we employed molecular docking to sort pentapeptides that can bind to Aβ₄₂, then performed molecular dynamics (MD) analyses, including analysis of the binding stability, interaction energy, and binding free energy to screen ligands. Transmission electron microscopy (TEM), circular dichroism (CD), thioflavin T (ThT) fluorescence detection of Aβ₄₂ polymerization, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the flow cytometry of reactive oxygen species (ROS) were carried out to evaluate the influence of pentapeptides on the aggregation and cell toxicity of Aβ_42. Two pentapeptides (TRRRR and ARRGR) were found to have strong effects on inhibiting the aggregation of Aβ₄₂ and reducing the toxicity of Aβ₄₂ secreted by SH-SY5Y cells, including cell death, reactive oxygen species (ROS) production, and apoptosis. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology Insights into Neurodegenerative Diseases: From Pathogenesis to Therapeutic Targets)

► Show Figures

Figure 1

Journal Description

Current Issues in Molecular Biology

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI