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Curr. Issues Mol. Biol., Volume 46, Issue 12 (December 2024) – 6 articles

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19 pages, 2439 KiB

Open AccessArticle

Characterization of a Cancer-Induced Bone Pain Model for Use as a Model of Cancer Cachexia

by Takuya Hasegawa, Kohichi Kawahara, Koji Sato, Yoshihisa Asano and Takehiko Maeda

Curr. Issues Mol. Biol. 2024, 46(12), 13364-13382; https://doi.org/10.3390/cimb46120797 (registering DOI) - 23 Nov 2024

Abstract

Cancer cachexia is a debilitating syndrome characterized by progressive weight loss, muscle wasting, and systemic inflammation. Despite the prevalence and severe consequences of cancer cachexia, effective treatments for this syndrome remain elusive. Therefore, there is a greater need for well-characterized animal models to identify novel therapeutic targets. Certain manifestations of cachexia, such as pain and depression, have been extensively studied using animal models of cancer-induced bone pain (CIBP). In contrast, other aspects of cachexia have received less attention in these models. To address this issue, we established the CIBP model by injecting Lewis lung carcinoma into the intramedullary cavity of the femur, observed cachexia-related symptoms, and demonstrated the utility of this model as a preclinical platform to study cancer cachexia. This model accurately recapitulates key features of cancer cachexia, including weight loss, muscle atrophy, adipose tissue depletion, CIBP, and anxiety. These findings suggest that psychological factors, in addition to physiological and metabolic factors, play significant roles in cancer cachexia development. Our model offers a valuable resource for investigating the underlying mechanisms of cancer cachexia and for developing innovative therapeutic strategies that target physical and psychological components. Full article

(This article belongs to the Section Molecular Medicine)

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17 pages, 8944 KiB

Open AccessArticle

Genome-Wide Development of InDel-SSRs and Association Analysis of Important Agronomic Traits of Taro (Colocasia esculenta) in China

by Rao Pan, Qianglong Zhu, Xinbi Jia, Bicong Li, Zihao Li, Yao Xiao, Sha Luo, Shenglin Wang, Nan Shan, Jingyu Sun, Qinghong Zhou and Yingjin Huang

Curr. Issues Mol. Biol. 2024, 46(12), 13347-13363; https://doi.org/10.3390/cimb46120796 - 22 Nov 2024

Abstract

Taro (Colocasia esculenta (L.) Schott) is a tropical tuber crop whose underground corms are used as an important staple food. However, due to a lack of molecular markers, the genetic diversity, germplasm identification, and molecular breeding of taro are greatly limited. In this study, high-density InDel-SSR molecular markers covering the whole genome were developed based on the resequencing data of taro core germplasm. A total of 1,805,634 InDel-SSR loci were identified, and 219 highly polymorphic markers with an average polymorphism information content PIC value of 0.428 were screened. Furthermore, a genetic diversity analysis of 121 taro germplasm resources was conducted based on 219 markers, dividing the resources into three groups. In addition, an association analysis showed that, of the multiple InDel-SSR markers, g13.52 and g12.82 were significantly associated with leaf area and average cormel weight, respectively; the candidate genes CeARF17 (EVM0014444) and CeGA20ox (EVM0001890) were related to cormel expansion; and we excavated the candidate genes CeXXT2 (EVM0016820) and CeLOG1 (EVM0017064), which regulate leaf development. The InDel-SSRs and candidate genes identified in this study are expected to provide important support for genetically improving and breeding new varieties of taro. Full article

(This article belongs to the Section Molecular Plant Sciences)

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19 pages, 4185 KiB

Open AccessArticle

Reverse Mutations in Pigmentation Induced by Sodium Azide in the IR64 Rice Variety

by Hsian-Jun Chen, Anuchart Sawasdee, Yu-Ling Lin, Min-Yu Chiang, Hsin-Yi Chang, Wen-Hsiung Li and Chang-Sheng Wang

Curr. Issues Mol. Biol. 2024, 46(12), 13328-13346; https://doi.org/10.3390/cimb46120795 - 22 Nov 2024

Abstract

Pigmentation in rice is due mainly to the accumulation of anthocyanins. Five color mutant lines, AZ1701, AZ1702, AZ1711, AZ1714, and AZ1715, derived from the sodium azide mutagenesis on the non-pigmented IR64 variety, were applied to study inheritance modes and genes for pigmentation. The mutant line AZ1711, when crossed with IR64, displays pigmentation in various tissues, exhibiting a 3:1 pigmented to non-pigmented ratio in the F₂ progeny, indicating a single dominant locus controlling pigmentation. Eighty-four simple sequence repeat (SSR) markers were applied to map the pigment gene using 92 F₂ individuals. RM6773, RM5754, RM253, and RM2615 markers are found to be linked to the color phenotype. RM253 explains 78% of the phenotypic variation, implying linkage to the pigmentation gene(s). Three candidate genes, OsC1 (MYB), bHLH, and 3GT, as anthocyanin biosynthesis-related genes, were identified within a 0.83 Mb region tightly linked to RM253. PCR cloning and sequencing revealed 10 bp and 72 bp insertions in the OsC1 and 3GT genes, respectively, restoring pigmentation as in wild rice. The 72 bp insertion is highly homologous to a sequence of Ty1-Copia retrotransposon and shows a particular secondary structure, suggesting that it was derived from the transposition of Ty1-Copia in the IR64 genome. Full article

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

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17 pages, 5639 KiB

Open AccessArticle

Comprehensive Transcriptomic and Physiological Insights into the Response of Root Growth Dynamics During the Germination of Diverse Sesame Varieties to Heat Stress

by Xiaoyu Su, Chunming Li, Yongliang Yu, Lei Li, Lina Wang, Dandan Lu, Yulong Zhao, Yao Sun, Zhengwei Tan and Huizhen Liang

Curr. Issues Mol. Biol. 2024, 46(12), 13311-13327; https://doi.org/10.3390/cimb46120794 - 22 Nov 2024

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Abstract

Heat stress constitutes a serious threat to sesame (Sesamum indicum L.). Root development during seed germination plays an essential role in plant growth and development. Nevertheless, the regulatory mechanisms underlying heat stress remain poorly understood. In this study, two sesame varieties differing in leaf heat tolerance (Zheng Taizhi 3 (heat-tolerant) and SP19 (heat-sensitive)) have been employed to investigate the impact of heat stress on root growth during germination. The results showed that heat stress significantly reduced the radicle length by 35.71% and 67.02% in Zheng Taizhi 3 and SP19, respectively, while germination rates remained unchanged. In addition, heat stress induced oxidative stress, as evidenced by increased reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and reduced indole-3-acetic acid (IAA) content, accompanied by enhanced antioxidant enzyme activities, including those of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the abscisic acid (ABA) content significantly increased in both varieties. However, the oxidation resistance in the roots of Zheng Taizhi 3 was enhanced compared to that of SP19 under heat stress, while IAA production was maintained and ABA content was reduced. A comparative transcriptome analysis identified 6164 and 6933 differentially expressed genes (DEGs) in Zheng Taizhi 3 and SP19, respectively, with 4346 overlapping DEGs. These DEGs included those related to stress tolerance, such as heat-shock proteins (HSPs), the antioxidant defense system, hormone signal transduction, and the biosynthetic pathway of phenylpropanoid. These findings provide insights into the physiological and molecular mechanisms underlying the adaptation of sesame to heat stress, which could inform breeding strategies for developing heat-tolerant sesame varieties. Full article

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

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15 pages, 8165 KiB

Open AccessArticle

Multiomics Analysis of Molecules Associated with Cancer in Mesenchymal-Stem-Cell-(MSC)-Derived Exosome-Treated Hepatocellular Carcinoma Cells

by Wen-Yong Gao, Chantana Boonyarat, Nutjakorn Samar, Benjabhorn Sethabouppha and Pornthip Waiwut

Curr. Issues Mol. Biol. 2024, 46(12), 13296-13310; https://doi.org/10.3390/cimb46120793 - 21 Nov 2024

Viewed by 220

Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer in humans, with an increasing incidence worldwide. The current study aimed to explore the molecular mechanisms that inhibit the proliferation of HepG2 cells, a hepatoblastoma-derived cell line. MSC-derived exosomes (UC-MSCs) were prepared with a median particle size (N50) of 135.8 nm. Concentrations of UC-MSCs ranging from 10 μg/mL to 1000 μg/mL were applied to HepG2 cell cultures and compared to untreated and anticancer drug-treated HepG2 cells. A combined approach was employed, integrating a proteomic analysis of UC-MSCs, metabolomic analysis of HepG2 cells, and transcriptomic profiling of HepG2 cells to decipher the inhibitory mechanisms of UC-MSC exosomes on HepG2 cell growth. Treatment with a high concentration of UC-MSCs led to a notable reduction in HepG2 cell viability, with survival decreasing by 65%. A proteomic analysis of UC-MSCs revealed enriched degranulation processes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in addition to the known exosomal pathways. Transcriptomic profiling showed distinct changes in the expression of genes related to hepatocellular diseases in UC-MSC-treated HepG2 cells, contrasting with changes observed in HepG2 cells treated with the chemotherapeutic agent doxorubicin (DOX). Combined with a metabolomic analysis, the detailed GO and KEGG pathway analyses indicated that pathways associated with neutrophil extracellular trap formation played a critical role in mediating protein degradation and suppressing central carbon metabolism in cancer cells. Our results revealed that the UC-MSC treatment mimicked molecular mechanisms similar to those involved in neutrophil extracellular trap formation, exhibiting effects on HepG2 cell growth suppression that differed from those of chemical cancer drugs. Notably, the UC-MSC treatment demonstrated that protein degradation in HepG2 cells was regulated through canonical signaling pathways activated by bacterial peptides in neutrophils. This research has provided valuable insights into the potential of MSC-derived exosomes as a therapeutic approach for cancer treatment in the future. Full article

(This article belongs to the Special Issue Metabolic Reprogramming of Immune Cells in Tumor Microenvironment)

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15 pages, 1097 KiB

Open AccessReview

Differentiation of Human Mesenchymal Stem Cells into Corneal Epithelial Cells: Current Progress

by Abdul Malik Setiawan and Taty Anna Kamarudin

Curr. Issues Mol. Biol. 2024, 46(12), 13281-13295; https://doi.org/10.3390/cimb46120792 - 21 Nov 2024

Viewed by 315

Abstract

The limited availability of corneal tissue grafts poses significant challenges in the treatment of corneal blindness. Novel treatment utilizes stem cell grafts transplanted from the healthy side of the cornea to the damaged side. However, this procedure is only possible for those who have one-sided corneal blindness. Human stem cells offer promising potential for corneal tissue engineering, providing an alternative solution. Among the different types of stem cells, mesenchymal stem cells (MSCs) stand out due to their abundance and ease of isolation. Human MSCs can be derived from bone marrow, adipose, and umbilical cord tissues. Differentiating MSC toward corneal tissue can be achieved through several methods including chemical induction and co-culture with adult corneal cells such as human limbal epithelial stem cells (LESCs) and human corneal epithelial cells (hTCEpi). Adipose-derived stem cells (ADSCs) are the most common type of MSC that has been studied for corneal differentiation. Corneal epithelial cells are the most common corneal cell type targeted by researchers for corneal differentiation. Chemical induction with small molecules, especially bone morphogenetic protein 4 (BMP4), all-trans retinoic acid (ATRA), and epidermal growth factor (EGF), has gained more popularity in corneal epithelial cell differentiation. This review highlights the current progress in utilizing MSCs for corneal differentiation studies, showcasing their potential to revolutionize treatments for corneal blindness. 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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