Journal of Molecular Histology最新文献

Gastric ulcers are one of the major public health burdens in the modern era, with increased complications that could be a result of alcohol abuse or H. pylori infection. In this study, we investigated the therapeutic potential and acute toxicity effects of Pterostilbene (PSB) in ethanol-mediated gastropathy, as well as its underlying molecular mechanism, in rats. Gastric ulcers are provoked by absolute ethanol (5 mL/kg, i.g.) in male Sprague–Dawley rats after receiving oral treatments: physiological saline (negative, 5 mL/kg), omeprazole (positive control, 20 mg/kg), and PSB (30 and 60 mg/kg). PSB pretreatment significantly alleviated clinical signs, reduced the macroscopic ulcer index, and improved gastric mucosal morphology, including gastric defense barriers (mucus and glycoprotein production). PSB Pretreatment improved ethanol-mediated microscopical alterations, as indicated by reduced submucosal oedema, decreased hemorrhagic/lesion areas, and restoration of mucosal integrity. PSB down-regulated apoptotic actions (reduced P53 and increased Bcl-2 protein expression), lowered inflammatory conditions (decreased TNF-α, IL-6, and increased IL-10), and limited oxidative stress tissue injuries (up-regulated SOD, CAT, and PGE2 while lowering MDA). The PSB gastroprotection may be linked to a strengthened gastric defense and anti-oxidative/anti-inflammatory pathways, ultimately curbing apoptotic actions by modulating death signals, P53, and Bcl-2 proteins. The outcomes present PSB as a viable nutraceutical and biopharmaceutical product for managing stomach disorders, including gastric ulcers.

The impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes significantly to osteoporosis (OP) pathogenesis. While Forkhead box p1 (FOXP1) is known to regulate stem cell differentiation, its specific role in BMSCs osteogenic differentiation during OP remains unclear. Here, BMSCs were cultured in osteogenic medium for 14 d to induce osteogenic differentiation. We found that FOXP1 was upregulated in BMSCs treated with osteogenic medium, and FOXP1 overexpression promoted BMSC osteogenic differentiation, whereas FOXP1 knockdown inhibited BMSCs osteogenic differentiation. Mechanistically, METTL14 mediated m6A methylation of FOXP1 mRNA, which was recognized by YTHDF1/YTHDF3 to enhance its mRNA stability. Notably, METTL14 overexpression promoted osteogenic differentiation of BMSCs, this effect was abolished by FOXP1 knockdown. The stabilized FOXP1 protein activated the Wnt/β-catenin signaling pathway to drive BMSC osteogenesis. In vivo, administration of FOXP1-overexpressing lentivirus in ovariectomized (OVX) mice significantly attenuated osteoporosis progression. Collectively, our findings reveal that METTL14-dependent m6A modification and YTHDF1/YTHDF3-mediated stabilization of FOXP1 alleviate osteoporosis in OVX mice through Wnt/β-catenin activation, positioning FOXP1 as a promising therapeutic target for postmenopausal osteoporosis.

Corneal alkali burns trigger the infiltration of inflammation-associated macrophages, which can potentially lead to vision impairment. Although Sinomenine (SIN) is recognized for its anti-inflammatory properties, its role on the polarization of macrophages and its effects on corneal alkali injury remain inadequately understood. In this study, corneal alkali damage was induced using NaOH. HE staining and immunohistochemistry were conducted to assess macrophage infiltration in corneal tissues. Macrophages were isolated via flow cytometry assay. Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of genes associated with macrophage polarization. The results indicated an increase in macrophage infiltration and M1 polarization in mice subjected to corneal alkali injury. Sinomenine treatment effectively inhibited the polarization of M1 macrophages in the cornea. In mice treated with Sinomenine post-injury, there was a reduction in the expression of the m6A methylation writer protein METTL3 in macrophages, which led to an upregulation of IRAKM expression. The elevated IRAKM expression subsequently inhibited the TLR4 inflammatory pathway and reduced corneal inflammatory cell infiltration, ultimately ameliorating corneal alkali burns. Sinomenine attenuates M1 macrophage polarization through upregulating IRAKM by inhibiting the expression of the m6A methylation writer protein METTL3 in macrophages, leading to enhanced outcomes in corneal alkali injuries.

Exosomes, nanosized extracellular vesicles ranging from 30 to 150 nm, have gained increasing attention as mediators of cell-to-cell communication. Within the islet microenvironment, exosomes mediate crosstalk among β-cells, immune cells, and endothelial cells, helping maintain islet integrity, modulate immune responses, and influence the progression of type 1 and type 2 diabetes. Because of their intrinsic role in cellular communication, exosomes are being explored as potential therapeutic tools. Engineered exosomes can be tailored to transport bioactive molecules, including insulin, peptides, or anti-inflammatory agents, directly to pancreatic cells. Such targeted delivery may enhance glycemic control while limiting immune-mediated β-cell destruction. Beyond therapy, exosomes are also being investigated as biomarkers, as their molecular cargo reflects disease-specific alterations, offering opportunities for early diagnosis and timely intervention. This review further examines the scope of exosome-based diagnostics and therapeutics, including advances in exosome engineering and stem cell–derived exosomal applications. Compared with conventional systems, exosomes offer superior targeting, fewer off-target effects, and low immunogenicity due to their natural biocompatibility. These attributes position exosomal therapy as a promising avenue for the development of personalized strategies in diabetes management. In addition, novel findings on exosomal microRNAs, proteins, and lipid components involved in β-cell survival, insulin signaling pathways, and islet inflammation are summarized. Together, these insights highlight the emerging relevance of exosome biology in understanding diabetes pathogenesis and shaping innovative therapeutic approaches.

Acute myeloid leukemia (AML) is a highly heterogeneous malignancy originating from prolonged abnormal proliferation of immature myeloid cells. Long non-coding RNAs (lncRNAs) are important regulators of AML progression. TMEM147-AS1 has been reported to be abnormally expressed in AML. This study aimed to further explore the roles of TMEM147-AS1 in AML and the possible mechanism. The expression of TMEM147-AS1 and miR-873-3p and its role in the clinical progression of AML were investigated. The diagnostic and prognostic value of TMEM147-AS1 in AML was assessed. The impacts of TMEM147-AS1 on AML cell function were examined. And the targeting relationship among TMEM147-AS1, miR-873-3p, and ZFX was predicted by databases and verified by dual-luciferase reporter assay. TMEM147-AS1 was upregulated in AML tissues and cell lines. High TMEM147-AS1 expression was significantly related to adverse karyotype, shorter overall survival time, and worse prognosis in AML patients. And TMEM147-AS1 can distinguish AML patients from healthy individuals with relatively high sensitivity and specificity. Furthermore, TMEM147-AS1 targeted miR-873-3p, which further targeted ZFX. TMEM147-AS1 promoted proliferation and inhibited apoptosis of AML cells through downregulating the inhibitory effect of miR-873-3p on ZFX expression. TMEM147-AS1 promotes AML progression via regulating the miR-873-3p/ZFX axis. TMEM147-AS1 is a promising diagnostic and prognostic indicator in AML.

The corpus callosum is exposed to many degenerative disorders, such as multiple sclerosis (MS), which results in impaired communication between the two cerebral hemispheres. In contrast to stem cells of other origins, adipose-derived mesenchymal stem cells (ADMSCs) are efficiently obtained. The intranasal route is a new emerging noninvasive, easily available route for drug administration. To evaluate the effects of intranasal administration of ADMSCs on a cuprizone induced demyelinated corpus callosum in a mouse model of MS with reference to the role of oligodendrocytes and microglia. To establish a model of demyelination, mice were fed a cuprizone-rich diet. After 4 weeks, ADMSCs were administered intranasally, and the mice were subsequently sacrificed two weeks later. The corpora callosa were collected and subjected to hematoxylin and eosin (H&E), immunohistochemical staining for oligodendrocyte precursor cells and microglia, transmission electron microscopic examination, and histomorphometric studies. Intranasally administered ADMSCs ameliorated the histopathological features of cuprizone induced demyelination. ADMSCs prevented myelin loss, increased the number of oligodendrocyte precursor cells, and decreased the abundance of active microglia. ADMSCs have beneficial effects on preserving the histopathological structure and function of the corpus callosum in mice with demyelinating disorders. The intranasal administration of ADMSCs might be an easy noninvasive approach for administration of drugs.

Inflammation, oxidative stress and the resulting mitochondrial dysfunction constitute a critical triad in colorectal cancer, whose dynamic interaction reveals valuable avenues for disease management. NAD + /NADH ratio deterioration contributes to the progression of multiple metabolic disorders, including cancer, as it is linked to the above pathological axis. This study investigated the effects of NADH in a 1,2-dimethylhydrazine (DMH)-induced mouse model of colon carcinogenesis, focusing on the hypothesis that NADH mitigates ACF formation and associated inflammatory and oxidative stress responses. The mice were treated with DMH to induce colon cancer and received moderate (50 mg/kg) or high (150 mg/kg) doses of NADH. The key endpoints included aberrant crypt foci (ACF) formation, hematological parameters, and inflammation and oxidative stress markers. DMH treatment resulted in increased ACF formation; and disrupted the colonic histological architecture. Markers of oxidative stress, including malondialdehyde and nitrites, were significantly elevated, whereas antioxidant defenses; such as superoxide dismutase, glutathione peroxidase, catalase, and glutathione, were reduced. Inflammation was evidenced by increased levels of TNF-α and IL-17 while a reduction in IFN-γ levels was noted. NADH administration, particularly at the moderate dose, mitigated these effects by reducing ACF formation (~ 53%), preserving hematological parameters, and restoring the oxidative and inflammatory balance. Additionally, NADH treatment partially improved colonic architecture by reducing dysplasia and maintaining epithelial integrity. These findings demonstrate for the first time that NADH, especially at moderate doses, effectively prevents DMH-induced colon carcinogenesis by preserving immune homeostasis, reducing inflammation, and restoring oxidative balance.

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Acquired resistance is the major clinical change for patients with ovarian cancer undergoing niraparib (NRP) treatment. Targeting NRP-resistant cells would be NRP offers an effective strategy for reversing resistance and inhibiting disease progression. NR4A3 is known as a tumor suppressor in multiple cancers, but its role in NRP resistance of ovarian cancer is still unclear. NRP-resistant ovarian cancer cell lines (A2780/NRP and OVCAR3/NRP) were established by gradually increasing NRP concentrations. The phenotype of resistant cell lines was characterized using proliferation, colony formation, and migration assays. RNA sequencing was performed to identify genes dysregulated in the resistant cell lines. We also performed gain- and loss-of-function assays to investigate the role of NR4A3 in NRP resistance. The resistance indices for A2780/NRP and OVCAR3/NRP were 8.95 and 4.42, respectively. These resistant cells exhibited slower proliferation and robust colony formation and migration abilities. NR4A3 exhibited the highest average log2 fold change among the candidates. Overexpression of NR4A3 sensitized the NRP-resistant cells and reduced their proliferation, colony formation, and migration capabilities, whereas downregulation of NR4A3 in the parental cells caused opposite results. Downregulation of NR4A3 contributes to NRP resistance, and activation of NR4A3 maybe a promising strategy to reverse NRP resistance.