Molecular Biology Reports最新文献

Introduction: The Hippo signaling pathway is an evolutionarily conserved, tumor suppressor, stem cell pathway. This is the very less explored pathway in Breast Cancer. It is a crucial regulator of several biological processes, such as organ size, differentiation, tissue homeostasis, cellular proliferation, and stemness. Interestingly, deregulation of this pathway leads to tumorigenesis. Hence, the present study aims to identify the role of the Hippo signaling pathway in Breast Cancer.

Materials and methods: The mRNA expression of the Hippo signaling pathway molecules was evaluated in 120 pre-therapeutic patients by quantitative real-time PCR. Statistical analysis was carried out using SPSS 23. The association between the gene expression and clinicopathological parameters was analyzed by the paired sample t-test, and Pearson chi-square test. ROC curve analysis was carried out using Med Cal. A p-value of ≤ 0.05 was considered statistically significant.

Results: The hippo signaling pathway contains 10 core components i.e.SAV1, MOB1A, MOB1B, MST1, MST2, LATS1, LATS2, YAP, TAZ, and TEAD1 which were downregulated in malignant tissues as compared to adjacent normal tissue in breast cancer. In the correlation of hippo signaling pathway molecules with clinico pathological parameters, only LATS1, MST1, and SAV1 were found to be significantly negatively associated with stages of Breast Cancer. MOB1B was found to be significantly positively correlated with stages of Breast Cancer. ROC curve analysis of YAP, TAZ, LATS2, and TEAD showed significant discrimination between adjacent normal and malignant tissue.

Conclusion: In the current study, all the molecules of the hippo signaling pathway i.e. YAP, TAZ, LATS1, LATS2, MST1, MST2, SAV1, MOB1, MOB1B, TEAD1 were downregulated in BC suggesting the activation of hippo pathway which played a significant role in tumor suppression.

Today, herbal drugs are prominent in the pharmaceutical industry due to their well-known therapeutic and side effects. Plant-based compounds often face limitations such as poor solubility, low bioavailability, and instability in physiological environments, restricting their therapeutic efficacy and delivery. Nanotechnology-based solutions, including nanoparticle formulations and advanced delivery systems like liposomes and transfersomes, address these issues by enhancing solubility, stability, bioavailability, and targeted delivery, thereby optimizing the therapeutic potential of phytoactive compounds. Neuroinflammation can be a cause of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, or amyotrophic lateral sclerosis. Consequently, there is a need for the optimal delivery of a pharmacological anti-inflammatory agents to the CNS. Thus, the non-invasive administration of a stable compound at a therapeutic concentration is needed to assure molecule crossing through the blood-brain barrier. Natural resources have more structural diversity and novelty than synthetic compounds, e.g. plant-derived drug products have higher molecular weights, incorporate more oxygen atoms, and are more complex. As a result, plant-derived products have unique features which can be used to effectively modulate neuroinflammation. Therefore, this review aims to identify herbal molecules capable of targeting neuroinflammation and present novel strategies for their efficient delivery.

Background: Controlling intestinal risk factors by consuming probiotics and modifying lifestyle with exercise modulates dietary damage. The aim of the present study was to investigate the effect of 6 weeks of aerobic exercise training and probiotic consumption on the expression of inflammatory genes and histopathological changes in the liver of rats with a high-fat diet model.

Methods and results: In this study, 40 male Wistar rats were divided into 5 groups: healthy control, high-fat diet (HFD), HFD with exercise (HFD + Exe), HFD with probiotic consumption (HFD + Prob), and HFD + Exe + Prob. Animals in the HFD group were first exposed to a special diet and after confirming liver tissue damage, they entered the main protocol. Animals in the exercise group performed aerobic exercise on a rodent treadmill for 6 weeks, 5 days a week. Animals in the probiotic group also received Lactobacillus bifidus by oral gavage after exercise. Finally, intestinal and liver tissue were removed and examined for histological and cellular examination. Based on the results, HFD caused tissue damage and fat infiltration in both intestinal and liver tissue. Also, inflammatory factors (IL-6 and IL-1β genes) in the liver tissue of this group increased significantly compared to the control group (p < 0.05). In contrast, probiotic intervention and aerobic exercise caused a significant decrease in IL-6 and IL-1β genes compared to the HFD group (p < 0.05).

Conclusion: The use of probiotic Lactobacillus bifidus along with exercise can neutralize inflammatory damage caused by a high-fat diet in liver tissue. However, further studies are needed in this field.

Background: Neuroinflammation and abnormal energy metabolism have been shown to significantly contribute to the progression of Alzheimer's disease (AD). Adenylate kinase 5 (AK5), an enzyme predominantly expressed in the brain regulates ATP metabolism, has an unclear role in energy metabolism and neuroinflammation in AD.

Methods: The AD datasets were derived from the GEO public database to analyze the expression levels of AK5 in AD and normal samples and to assess the relationship between AK5 expression and the clinical characteristics of AD patients. Functional enrichment analysis was employed to investigate the effects of changes in AK5 expression on energy metabolism and immunoinflammation in AD, as well as the underlying mechanisms. Moreover, the influence of AK5 expression variations on oligodendrocyte development was assessed, and the predicted outcomes were validated through cellular experiments.

Results: Bioinformatic analysis revealed that AK5 was lowly expressed in AD olfactory lobe tissues, accompanied by increased immunoinflammation and apoptosis. Increased expression of AK5 was associated with the activation of AMPK signaling, enhanced oxidative phosphorylation, and overall stimulation of energy metabolism. In oligodendrocytes treated with Aβ1-42, overexpression of AK5 resulted in elevated levels of P-AMPK, SIRT1, and BCL-2 proteins, while reducing the levels of BAX, CASPASE-3, and NF-κB proteins. This modulation activated AMPK signaling, thereby inhibiting neuroinflammation and apoptosis. In contrast, low levels of AK5 expression during early differentiation triggered inflammatory responses and increased apoptosis in oligodendrocytes.

Conclusion: AK5 inhibits AD oligodendrocyte apoptosis by activating the AMPK signaling pathway.

A vitamin D₃ metabolite 1α,25-dihydroxyvitamin D₃ exhibits numerous hormonal actions to various tissues and cells such as induction of calcium ion absorption, bone metabolism, activation of innate immune system. Because hormonal actions of 1α,25-dihydroxyvitamin D₃ are too complex, it is difficult to better understand overall views of intermolecular networks on the cell activation by 1α,25-dihydroxyvitamin D₃. In this review we concisely outline the most fundamental molecular mechanisms for the cell activation by 1α,25-dihydroxyvitamin D₃ based on the previous and recent studies. In addition, we expound biological activity of 25-hydroxyvitamin D₃ and 1α,25-dihydroxyvitamin D₃ that differs from hormonal actions. In addition, recent studies by our group revealed that vitamin D decomposition products confer extremely selective bactericidal action to Helicobacter pylori, a pathogen causative gastritis, peptic ulcers and gastric cancers in human. Vitamin D decomposition products induce the bacteriolysis as targeting of characteristic glycerophospholipids composed of the bacterial biomembranes. In the future we will expect to be capable of developing novel antibacterial agents targeting a characteristic glycerophospholipid of the pathogenic bacteria using vitamin D decomposition products as fundamental structures.

Background: Cancer cells can modulate the expression of many proteins that are essential for supporting their uncontrolled proliferation. Heat shock protein 90 (HSP90) is ubiquitously expressed in most cell types and participates in controlling many survival pathways. Cancer cells utilize HSP90 in order to prolong their survival, thus they tend to overexpress it. Based on its importance for cancer cells, we aim to investigate the molecular mechanisms that link HSP90 inhibition in colon cancer cells with oxidative stress and mitochondrial stress-related regulators.

Materials and methods: We used RKO colon cancer cells, blocking HSP90 with the inhibitor AT13387 and HSP90 siRNA. Cell proliferation and apoptosis were measured via CCK8 ELISA and Fluorescent Apoptosis Assays. Western blotting and immunocytochemistry assessed oxidative and mitochondrial stress markers BNIP3, PINK1, GP91/NOX2, and IRE1α in treated cells.

Results: Our findings reveal that inhibiting HSP90 with AT13387 reduces RKO cell viability by suppressing proliferation and enhancing Annexin-V expression, indicative of increased apoptosis. This rise in apoptosis is associated with PINK1 downregulation and BNIP3 upregulation, markers of mitochondrial dysfunction and oxidative stress, respectively. Additionally, AT13387 treatment elevated the protein level of GP91, a marker of oxidative stress, and IRE1α, a marker of ER stress. Similarly, genetic knockdown of HSP90 in RKO cells produced comparable effects, including reduced cell survival and a decreased PINK1/BNIP3 ratio.

Conclusion: Targeting HSP90 in colon cancer cells disrupts their survival by decreasing PINK1 and increasing BNIP3, which activates oxidative and endoplasmic reticulum stress, ultimately triggering apoptosis.

Background: Mitochondrial genomes among Medusozoa show considerable variation in the class Hydrozoa, and many phylogenetic relationships inside the subphylum remain still unresolved. Stylasteridae, one of the most species-rich families among hydrozoans, characterized by a calcareous skeleton, lacks mitochondrial genomic information, limiting our understanding of their evolution and phylogenetic position within Hydrozoa.

Methods and results: This study present the first mitochondrial genome of two stylasterid species from the genus Errina (E. aspera and E. atlantica). Total genomic DNA was extracted and sequenced using Illumina NovaSeq 6000 and mitochondrial genomes were assembled and annotated using two different methods. Results hypothesized linear genomes of 14,938 bp and 14,969 bp respectively, containing 13 protein-coding genes, 2 transfer RNA genes, and 2 ribosomal RNA genes. The gene order was congruent with other Filifera, but lacking the cox1 duplication, transposition, and inversion common in other hydrozoans. Phylogenetic analyses confirmed the position of stylasterids as a sister group to Hydractiniidae within the Filifera suborder.

Conclusions: This study provides the first information about the stylasterid mitochondrial genome structure. Moreover, the phylogenetic analysis confirms the phylogenetic position of Hydractiniidae as sister family of Stylasteridae. The new findings have highlighted the importance of sequencing additional genomic data to better unravel the evolutionary history of this significant family.

Exploring the complex world of microRNA (miRNA) biogenesis and functions in plants is essential for understanding their diverse regulatory mechanisms. This review highlights the processes involved in miRNA biogenesis and their crucial roles in growth and development of plant, stress responses, and nutrient homeostasis. miRNAs play a central role in various developmental processes, including the transition from the juvenile to adult stage, the growth of shoot apical meristem, leaf and floral morphogenesis, and the determination of flowering time. By presenting the current state of research, we focus on the vital role of computational tools and databases in deciphering the regulatory networks controlled by miRNAs, which helps us navigate the intricate world of plant biology. Furthermore, it stresses the importance of experimental validation techniques in confirming computational predictions, ensuring that miRNA research is reliable and robust. As the field continues to grow, this review emphasizes the urgent need for integrated approaches, to deepen our knowledge of plant miRNA biology and its implications. These insights will pave the way for advancements in crop improvement, stress resilience, and biotechnological innovations.

Seed dormancy, a complex trait that is influenced by both nuclear and cytoplasmic factors, poses a significant challenge to agricultural productivity. Conventional dormancy-breaking techniques, including mechanical, physiological, and chemical methods, often yield inconsistent results, impair seed quality, and lack precision. This has necessitated exploration of more targeted and efficient approaches. CRISPR-based gene editing has emerged as a promising tool for the precise regulation of seed dormancy without compromising seed viability or sustainability. Although CRISPR has been successfully applied to modify genes that govern physiological traits in various crops, its use in dormancy regulation remains in the early stages. This review examines recent advancements in CRISPR-based approaches for modulating seed dormancy and discusses key gene targets, modification techniques, and the resulting effects. We also consider the future potential of CRISPR to enhance dormancy control across diverse crop species.