Current Issues in Molecular Biology

21 pages, 3556 KiB

Open AccessReview

Aquaporin Modulation by Cations, a Review

by Robin Mom, Vincent Mocquet, Daniel Auguin and Stéphane Réty

Curr. Issues Mol. Biol. 2024, 46(8), 7955-7975; https://doi.org/10.3390/cimb46080470 (registering DOI) - 24 Jul 2024

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Abstract

Aquaporins (AQPs) are transmembrane channels initially discovered for their role in water flux facilitation through biological membranes. Over the years, a much more complex and subtle picture of these channels appeared, highlighting many other solutes accommodated by AQPs and a dense regulatory network [...] Read more.

Aquaporins (AQPs) are transmembrane channels initially discovered for their role in water flux facilitation through biological membranes. Over the years, a much more complex and subtle picture of these channels appeared, highlighting many other solutes accommodated by AQPs and a dense regulatory network finely tuning cell membranes’ water permeability. At the intersection between several transduction pathways (e.g., cell volume regulation, calcium signaling, potassium cycling, etc.), this wide and ancient protein family is considered an important therapeutic target for cancer treatment and many other pathophysiologies. However, a precise and isoform-specific modulation of these channels function is still challenging. Among the modulators of AQPs functions, cations have been shown to play a significant contribution, starting with mercury being historically associated with the inhibition of AQPs since their discovery. While the comprehension of AQPs modulation by cations has improved, a unifying molecular mechanism integrating all current knowledge is still lacking. In an effort to extract general trends, we reviewed all known modulations of AQPs by cations to capture a first glimpse of this regulatory network. We paid particular attention to the associated molecular mechanisms and pinpointed the residues involved in cation binding and in conformational changes tied up to the modulation of the channel function. Full article

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

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11 pages, 4297 KiB

Open AccessArticle

ALA Promotes Sucrose Accumulation in Early Peach Fruit by Regulating SPS Activity

by Zheng Chen, Xin Guo, Jinhua Du and Mingliang Yu

Curr. Issues Mol. Biol. 2024, 46(8), 7944-7954; https://doi.org/10.3390/cimb46080469 (registering DOI) - 24 Jul 2024

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Abstract

5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase [...] Read more.

5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase in sugar content in fruit remains unclear. In this study, we found that ALA significantly promoted sucrose accumulation and SPS (sucrose phosphate synthase) activity in peach fruit. At 14, 28, 42, 50 and 60 days after ALA treatment, sucrose content of fruit was increased by 23%, 43%, 37%, 40% and 16%, respectively, compared with control treatment, and SPS enzyme activity was increased by 21%, 28%, 47%, 37% and 29%, respectively. Correlation analysis showed that the sucrose content of peach fruit under ALA treatment was significantly positively correlated with SPS activity. Subsequently, bioinformatics was used to identify SPS gene family members in peach fruit, and it was found that there were four members of the PpSPS gene family, distributed on chromosomes 1, 7 and 8, named PpSPS1, PpSPS2, PpSPS3 and PpSPS4, respectively. The results of qRT-PCR showed that PpSPS2 and PpSPS3 were highly expressed in response to ALA during fruit development, and the expression of PpSPS2 was positively correlated with SPS activity and sucrose accumulation in peach fruit. The results of tobacco subcellular localization showed that PpSPS2 was mainly distributed in the cytoplasm and nucleus, while PpSPS3 was mainly distributed in the nucleus. The results of this study will lay the foundation for further study on the functions of PpSPS and the regulation of sugar metabolism during the development and ripening of peach fruit by ALA. Full article

(This article belongs to the Section Molecular Plant Sciences)

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49 pages, 2460 KiB

Open AccessReview

Capsaicin: Emerging Pharmacological and Therapeutic Insights

by Elena Madalina Petran, Argyrios Periferakis, Lamprini Troumpata, Aristodemos-Theodoros Periferakis, Andreea-Elena Scheau, Ioana Anca Badarau, Konstantinos Periferakis, Ana Caruntu, Ilinca Savulescu-Fiedler, Romina-Marina Sima, Daniela Calina, Carolina Constantin, Monica Neagu, Constantin Caruntu and Cristian Scheau

Curr. Issues Mol. Biol. 2024, 46(8), 7895-7943; https://doi.org/10.3390/cimb46080468 (registering DOI) - 24 Jul 2024

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Abstract

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; [...] Read more.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin’s anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions. Full article

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

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18 pages, 5224 KiB

Open AccessArticle

Injection of Adipose-Derived Mesenchymal Stem/Stromal Cells Suppresses Muscle Atrophy Markers and Adipogenic Markers in a Rat Fatty Muscle Degeneration Model

by Sai Koung Ngeun, Miki Shimizu and Masahiro Kaneda

Curr. Issues Mol. Biol. 2024, 46(8), 7877-7894; https://doi.org/10.3390/cimb46080467 (registering DOI) - 24 Jul 2024

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Abstract

Fatty muscle degeneration and muscle atrophy have not been successfully treated due to their irreversible pathology. This study evaluated the efficacy of rat adipose-derived mesenchymal stem/stromal cells (ADP MSCs) in treating fatty muscle degeneration (FD). A total of 36 rats were divided into [...] Read more.

Fatty muscle degeneration and muscle atrophy have not been successfully treated due to their irreversible pathology. This study evaluated the efficacy of rat adipose-derived mesenchymal stem/stromal cells (ADP MSCs) in treating fatty muscle degeneration (FD). A total of 36 rats were divided into three groups: the control (C) group (n = 12); FD model group, generated by sciatic nerve crushing (n = 12); and the group receiving ADP MSC treatment for FD (FD+MSCs) (n = 12). In Group FD+MSCs, ADP MSCs were injected locally into the gastrocnemius muscle one week after the FD model was created (Day 8). On Day 22 (n = 18) and Day 43 (n = 18), muscle morphology, histopathology, and molecular analyses (inflammation, muscle atrophy, adipocytes, and muscle differentiation markers) were performed. In Group FD+MSCs, the formation of immature myofibers was observed on Day 22, and mitigation of fatty degeneration and muscle atrophy progression was evident on Day 43. Gene expression of muscle atrophy markers (FBXO32, TRIM63, and FOXO1) and adipogenic markers (ADIPOQ, PPARG, FABP4, and PDGFRA) was lower in Group FD+MSCs than Group FD on Day 43. ADP MSCs induce anti-inflammatory effects, inhibit fat accumulation, and promote muscle regeneration, highlighting their potential as promising therapy for FD and atrophy. Full article

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

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15 pages, 3373 KiB

Open AccessArticle

Identifying Universal Fish Biomarker Genes in Response to PCB126 Exposure by Comparative Transcriptomic Analyses

by Ira Agrawal, Ai Qi Lee and Zhiyuan Gong

Curr. Issues Mol. Biol. 2024, 46(8), 7862-7876; https://doi.org/10.3390/cimb46080466 (registering DOI) - 23 Jul 2024

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Abstract

Water pollution remains a major environmental concern, with increased toxic by-products being released into water bodies. Many of these chemical contaminants persist in the environment and bio-accumulate in aquatic organisms. At present, toxicological tests are mostly based on laboratory tests, and effective methods [...] Read more.

Water pollution remains a major environmental concern, with increased toxic by-products being released into water bodies. Many of these chemical contaminants persist in the environment and bio-accumulate in aquatic organisms. At present, toxicological tests are mostly based on laboratory tests, and effective methods for monitoring wild aquatic environments remain lacking. In the present study, we used a well-characterized toxic chemical, 3,3′,4,4′,5-polychlorinated biphenyl (PCB126), as an example to try to identify common biomarker genes to be used for predictive toxicity of this toxic substance. First, we used two laboratory fish models, the zebrafish (Danio rerio) and medaka (Oryzias latipes), to expose PCB126 to obtain liver transcriptomic data by RNA-seq. Comparative transcriptomic analyses indicated generally conserved and concerted changes from the two species, thus validating the transcriptomic data for biomarker gene selection. Based on the common up- and downregulated genes in the two species, we selected nine biomarker genes to further test in other fish species. The first validation experiment was carried out using the third fish species, Mozambique tilapia (Oreochromis mossambicus), and essentially, all these biomarker genes were validated for consistent responses with the two laboratory fish models. Finally, to develop universal PCR primers suitable for potentially all teleost fish species, we designed degenerate primers and tested them in the three fish species as well as in another fish species without a genomic sequence available: guppy (Poecilia reticulata). We found all the biomarker genes showed consistent response to PCB126 exposure in at least 50% of the species. Thus, our study provides a promising strategy to identify common biomarker genes to be used for teleost fish analyses. By using degenerate PCR primers and analyzing multiple biomarker genes, it is possible to develop diagnostic PCR arrays to predict water contamination from any wild fish species sampled in different water bodies. Full article

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

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16 pages, 887 KiB

Open AccessHypothesis

The Current Landscape of Hypotheses Describing the Contribution of CD4+ Heterogeneous Populations to ALS

by Mariusz Sacharczuk, Michel-Edwar Mickael, Norwin Kubick, Agnieszka Kamińska, Jarosław Olav Horbańczuk, Atanas G. Atanasov, Piotr Religa and Michał Ławiński

Curr. Issues Mol. Biol. 2024, 46(8), 7846-7861; https://doi.org/10.3390/cimb46080465 (registering DOI) - 23 Jul 2024

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Abstract

Amyotrophic Lateral Sclerosis (ALS) is a poorly understood and fatal disease. It has a low prevalence and a 2–4 year survival period. Various theories and hypotheses relating to its development process have been proposed, albeit with no breakthrough in its treatment. Recently, the [...] Read more.

Amyotrophic Lateral Sclerosis (ALS) is a poorly understood and fatal disease. It has a low prevalence and a 2–4 year survival period. Various theories and hypotheses relating to its development process have been proposed, albeit with no breakthrough in its treatment. Recently, the role of the adaptive immune system in ALS, particularly CD4+ T cells, has begun to be investigated. CD4+ T cells are a heterogeneous group of immune cells. They include highly pro-inflammatory types such as Th1 and Th17, as well as highly anti-inflammatory cells such as Tregs. However, the landscape of the role of CD4+ T cells in ALS is still not clearly understood. This review covers current hypotheses that elucidate how various CD4+ T cells can contribute to ALS development. These hypotheses include the SWITCH model, which suggests that, in the early stages of the disease, Tregs are highly capable of regulating the immune response. However, in the later stages of the disease, it seems that pro-inflammatory cells such as Th1 and Th17 are capable of overwhelming Treg function. The reason why this occurs is not known. Several research groups have proposed that CD4+ T cells as a whole might experience aging. Others have proposed that gamma delta T cells might directly target Tregs. Additionally, other research groups have argued that less well-known CD4+ T cells, such as Emoes+ CD4+ T cells, may be directly responsible for neuron death by producing granzyme B. We propose that the ALS landscape is highly complicated and that there is more than one feasible hypothesis. However, it is critical to take into consideration the differences in the ability of different populations of CD4+ T cells to infiltrate the blood–brain barrier, taking into account the brain region and the time of infiltration. Shedding more light on these still obscure factors can help to create a personalized therapy capable of regaining the balance of power in the battle between the anti-inflammatory and pro-inflammatory cells in the central nervous system of ALS patients. Full article

(This article belongs to the Special Issue The Molecular Roles of CD4+ T Cell Subsets in Neuropathological Diseases—Unraveling Diverse Interactions and Therapeutic Potentials)

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14 pages, 3201 KiB

Open AccessArticle

Endothelin-3 Suppresses Luteinizing Hormone Receptor Expression by Regulating the cAMP-PKA Pathway in Hen Granulosa Cells

by Yurong Tai, Deping Han, Xue Yang, Ganxian Cai, Huaiyu Li, Junying Li and Xuemei Deng

Curr. Issues Mol. Biol. 2024, 46(8), 7832-7845; https://doi.org/10.3390/cimb46080464 (registering DOI) - 23 Jul 2024

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Abstract

Previous research identified the expression of EDN3 in granulosa cells of preovulatory follicles in chickens. Notably, the expression level of EDN3 in Silky Fowl with low egg-laying performance was significantly higher than that in high-yield laying breed White Leghorn. Given the crucial role [...] Read more.

Previous research identified the expression of EDN3 in granulosa cells of preovulatory follicles in chickens. Notably, the expression level of EDN3 in Silky Fowl with low egg-laying performance was significantly higher than that in high-yield laying breed White Leghorn. Given the crucial role of granulosa cells in follicular development and maturation, it is very important to study the effect of EDN3 on the biological function of granular cells. In this study, an EDN3 overexpression plasmid was constructed and transfected into granular cells. The viability of these cells was detected using quantiative (qPCR), Cell Counting Kit-8 (CCK8), and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Gonadal hormone synthesis was detected using enzyme-linked immunosorbent assay (ELISA) techniques. Finally, transcriptome sequencing was employed to identify differentially expressed genes. Result showed thatoverexpression of EDN3 was observed to promote cell viability. In addition, it significantly inhibits the expressions of LHR and cAMP-PKA signaling pathways. Cell transcriptome sequencing data displayed that EDN3 can upregulate energy metabolism and immune-related signaling pathways, whereas follicle maturation and the GnRH signaling pathway were downregulated. In conclusion, this study demonstrates that EDN3 can enhance granulosa cell viability and inhibit the expression of LHCGR, a process likely mediated through the cAMP-PKA signaling pathway. However, further evidence is required to substantiate the regulatory relationship between EDN3 and the cAMP-PKA signaling pathway. Full article

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

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20 pages, 854 KiB

Open AccessReview

The Microbiota in Cancer: A Secondary Player or a Protagonist?

by Ana María Gómez García, Francisco López Muñoz and Eduardo García-Rico

Curr. Issues Mol. Biol. 2024, 46(8), 7812-7831; https://doi.org/10.3390/cimb46080463 (registering DOI) - 23 Jul 2024

Viewed by 136

Abstract

The intestinal microbiota and the human body are in a permanent interaction. There is a symbiotic relationship in which the microbiota plays a vitally important role in the performance of numerous functions, including digestion, metabolism, the development of lymphoid tissue, defensive functions, and [...] Read more.

The intestinal microbiota and the human body are in a permanent interaction. There is a symbiotic relationship in which the microbiota plays a vitally important role in the performance of numerous functions, including digestion, metabolism, the development of lymphoid tissue, defensive functions, and other processes. It is a true metabolic organ essential for life and has potential involvement in various pathological states, including cancer and pathologies other than those of a digestive nature. A growing topic of great interest for its implications is the relationship between the microbiota and cancer. Dysbiosis plays a role in oncogenesis, tumor progression, and even the response to cancer treatment. The effect of the microbiota on tumor development goes beyond a local effect having a systemic effect. Another aspect of great interest regarding the intestinal microbiota is its relationship with drugs, modifying their activity. There is increasing evidence that the microbiota influences the therapeutic activity and side effects of antineoplastic drugs and also modulates the response of several tumors to antineoplastic therapy through immunological circuits. These data suggest the manipulation of the microbiota as a possible adjuvant to improve oncological treatment. Is it possible to manipulate the microbiota for therapeutic purposes? Full article

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

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17 pages, 770 KiB

Open AccessReview

Phagocytosis Checkpoints in Glioblastoma: CD47 and Beyond

by Amber Afzal, Zobia Afzal, Sophia Bizink, Amanda Davis, Sara Makahleh, Yara Mohamed and Salvatore J. Coniglio

Curr. Issues Mol. Biol. 2024, 46(8), 7795-7811; https://doi.org/10.3390/cimb46080462 (registering DOI) - 23 Jul 2024

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Abstract

Glioblastoma multiforme (GBM) is one of the deadliest human cancers with very limited treatment options available. The malignant behavior of GBM is manifested in a tumor which is highly invasive, resistant to standard cytotoxic chemotherapy, and strongly immunosuppressive. Immune checkpoint inhibitors have recently [...] Read more.

Glioblastoma multiforme (GBM) is one of the deadliest human cancers with very limited treatment options available. The malignant behavior of GBM is manifested in a tumor which is highly invasive, resistant to standard cytotoxic chemotherapy, and strongly immunosuppressive. Immune checkpoint inhibitors have recently been introduced in the clinic and have yielded promising results in certain cancers. GBM, however, is largely refractory to these treatments. The immune checkpoint CD47 has recently gained attention as a potential target for intervention as it conveys a “don’t eat me” signal to tumor-associated macrophages (TAMs) via the inhibitory SIRP alpha protein. In preclinical models, the administration of anti-CD47 monoclonal antibodies has shown impressive results with GBM and other tumor models. Several well-characterized oncogenic pathways have recently been shown to regulate CD47 expression in GBM cells and glioma stem cells (GSCs) including Epidermal Growth Factor Receptor (EGFR) beta catenin. Other macrophage pathways involved in regulating phagocytosis including TREM2 and glycan binding proteins are discussed as well. Finally, chimeric antigen receptor macrophages (CAR-Ms) could be leveraged for greatly enhancing the phagocytosis of GBM and repolarization of the microenvironment in general. Here, we comprehensively review the mechanisms that regulate the macrophage phagocytosis of GBM cells. Full article

(This article belongs to the Special Issue Future Challenges of Targeted Therapy of Cancers: 2nd Edition)

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13 pages, 2544 KiB

Open AccessArticle

Astragalus Polysaccharides and Metformin May Have Synergistic Effects on the Apoptosis and Ferroptosis of Lung Adenocarcinoma A549 Cells

by I-Yun Lee, Ting-Chung Wang, Yu-Jen Kuo, Wei-Tai Shih, Pei-Rung Yang, Cheng-Ming Hsu, Yu-Shih Lin, Ren-Shyang Kuo and Ching-Yuan Wu

Curr. Issues Mol. Biol. 2024, 46(8), 7782-7794; https://doi.org/10.3390/cimb46080461 (registering DOI) - 23 Jul 2024

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Abstract

Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin [...] Read more.

Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma. Full article

(This article belongs to the Section Molecular Plant Sciences)

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Curr. Issues Mol. Biol., Volume 46, Issue 8 (August 2024) – 10 articles

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