Experimental & Molecular Medicine

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date...

N6 -adenosine methylation (m6 A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6 A methyltransferases modulate m6 A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6 A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2...

Interleukin-33 (IL-33), a member of the IL-1 family, is a cytokine released in response to tissue damage and is recognized as an alarmin. The multifaceted roles of IL-33 in tumor progression have sparked controversy within the scientific community. However, most findings generally indicate that endogenous IL-33 has a protumor effect, while exogenous IL-33 often has an antitumor effect in most cases. This review covers the general characteristics of IL-33 and its effects on tumor growth, with detailed information on the immunological mechanisms associated with dendritic cells (DCs)...

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain...

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide, and the identification of novel treatment targets and prognostic biomarkers is urgently needed because of its unsatisfactory prognosis. Regulator of G-protein signaling 19 (RGS19) is a multifunctional protein that regulates the progression of various cancers. However, the specific function of RGS19 in HCC remains unclear. The expression of RGS19 was determined in clinical HCC samples. Functional and molecular biology experiments involving RGS19 were performed to explore the potential mechanisms of RGS19 in HCC...

No abstract text is available yet for this article.

Methyltransferase-like 3 (METTL3) is a crucial element of N6-methyladenosine (m6 A) modifications and has been extensively studied for its involvement in diverse biological and pathological processes. In this study, we explored how METTL3 affects the differentiation of stem cells from the apical papilla (SCAPs) into odonto/osteoblastic lineages through gain- and loss-of-function experiments. The m6 A modification levels were assessed using m6 A dot blot and activity quantification experiments. In addition, we employed Me-RIP microarray experiments to identify specific targets modified by METTL3...

Interleukin-9 (IL-9) is a multifunctional cytokine with roles in a broad cross-section of human diseases. Like many cytokines, IL-9 is transcriptionally regulated by a group of noncoding regulatory elements (REs) surrounding the IL9 gene. These REs modulate IL-9 transcription by forming 3D loops that recruit transcriptional machinery. IL-9-promoting transcription factors (TFs) can bind REs to increase locus accessibility and permit chromatin looping, or they can be recruited to already accessible chromatin to promote transcription...

Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages...

Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2...

No abstract text is available yet for this article.

The etiology of preeclampsia (PE), a severe complication of pregnancy with several clinical manifestations and a high incidence of maternal and fetal morbidity and mortality, remains unclear. This issue is a major hurdle for effective treatment strategies. We recently demonstrated that PE exhibits an Alzheimer-like etiology of impaired autophagy and proteinopathy in the placenta. Targeting of these pathological pathways may be a novel therapeutic strategy for PE. Stimulation of autophagy with the natural disaccharide trehalose and its lacto analog lactotrehalose in hypoxia-exposed primary human trophoblasts restored autophagy, inhibited the accumulation of toxic protein aggregates, and restored the ultrastructural features of autophagosomes and autolysosomes...

Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and is often characterized by allodynia. Although neuron-independent mechanisms of hyperexcitability have been investigated, the contribution of astrocyte-neuron interactions remains unclear. Here, we show evidence of reactive astrocytes and their excessive GABA release in the spinal dorsal horn, which paradoxically leads to the tonic excitation of neighboring neurons in a neuropathic pain model. Using multiple electrophysiological methods, we demonstrated that neuronal hyperexcitability is attributed to both increased astrocytic GABA synthesis via monoamine oxidase B (MAOB) and the depolarized reversal potential of GABA-mediated currents (EGABA ) via the downregulation of the neuronal K+ /Cl- cotransporter KCC2...

No abstract text is available yet for this article.

Preeclampsia is caused by placental hypoxia and systemic inflammation and is associated with reduced placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS) levels. The molecular signaling axes involved in this process may play a role in the pathogenesis of preeclampsia. Here, we found that hypoxic exposure increased hypoxia-inducible factor-1α (HIF-1α)/Twist1-mediated miR-214-3p biogenesis in trophoblasts, suppressing PlGF production and trophoblast invasion. TNF-α stimulation increased NF-κB-dependent miR-214-3p expression in endothelial cells, impairing eNOS expression and causing endothelial dysfunction...

Recent progress in the investigation of microRNA (miRNA) biogenesis and the miRNA processing machinery has revealed previously unknown roles of posttranscriptional regulation in gene expression. The molecular mechanistic interplay between miRNAs and their regulatory factors, RNA-binding proteins (RBPs) and exoribonucleases, has been revealed to play a critical role in tumorigenesis. Moreover, recent studies have shown that the proliferation of hepatocellular carcinoma (HCC)-causing hepatitis C virus (HCV) is also characterized by close crosstalk of a multitude of host RBPs and exoribonucleases with miR-122 and its RNA genome, suggesting the importance of the mechanistic interplay among these factors during the proliferation of HCV...

Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis...

The glycerol 3-phosphate shuttle (GPS) is composed of two different enzymes: cytosolic NAD+ -linked glycerol 3-phosphate dehydrogenase 1 (GPD1) and mitochondrial FAD-linked glycerol 3-phosphate dehydrogenase 2 (GPD2). These two enzymes work together to act as an NADH shuttle for mitochondrial bioenergetics and function as an important bridge between glucose and lipid metabolism. Since these genes were discovered in the 1960s, their abnormal expression has been described in various metabolic diseases and tumors...

Biomedical research on the brain has led to many discoveries and developments, such as understanding human consciousness and the mind and overcoming brain diseases. However, historical biomedical research on the brain has unique characteristics that differ from those of conventional biomedical research. For example, there are different scientific interpretations due to the high complexity of the brain and insufficient intercommunication between researchers of different disciplines owing to the limited conceptual and technical overlap of distinct backgrounds...

Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes...