Journal of Molecular Histology最新文献

Nanoparticles are the fundamental building blocks of nanotechnology with numerous scientific applications. New advancements in nanotechnology have revealed uses for nanoparticles in various medicinal applications. This study investigated the chemoprotective effects of naringin-dextrin nanoparticles (NNPs) against diethylnitrosamine (DEN)-induced cardio-nephrotoxicity in Wistar rats. Cardio-nephrotoxicity was induced in Wistar rats via intraperitoneal DEN injection (150 mg/kg body weight (b.w.) per week) for 2 weeks, followed by oral administration of 2-acetylaminofluorene (2AAF) (20 mg/kg b.w.) four times per week for 3 weeks. Rats were then treated every other day for 24 weeks with either 10 mg/kg body weight of naringin (Nar) or 10 mg/kg body weight of NNPs. Nar and NNP treatments reduced biochemical markers of heart and kidney and improved tissue morphology compared to the DEN-treated group. These results were linked to a notable reduction in malondialdehyde (MDA) and nitric oxide (NO) levels, upregulation of antioxidant enzyme superoxide dismutase (SOD) activity, and enhanced glutathione (GSH) and nuclear factor erythroid 2–related factor 2 protein (NRF2) expression in the heart and kidneys. Nar and NNPs exerted an anti-inflammatory effect, manifested by a decrease in heart and kidney protein expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), with a concurrent increase in interleukin-4 (IL-4) expression, though this effect was more potent with NNPs than Nar. Regarding the effect on apoptosis, both Nar and NNPs significantly reduced the protein expression of p53 and caspase-3. Nar and NNPs effectively improved oxidative stress, inflammation, and tissue damage associated with DEN/AAF-induced cardio-nephrotoxicity.

Endometrial carcinoma is among the most common female malignancies. Many prognostic factors of endometrial carcinoma are proposed to predict survival in endometrial carcinoma patients. Cyclin D1 has been implicated in many malignancies including gastrointestinal and breast carcinoma. To correlate the immunohistochemical expression of Cyclin D1 in endometrial carcinoma with the different clinicopathological parameters. Forty-five cases of endometrial carcinoma with different histological subtypes and grades were included. Cyclin D1 expression was immunohistochemically tested. For each case, the predominant intensity was recorded, the density (as the percentage of positively stained cells irrespective of intensity) and H-score were recorded. Moreover, immunohistochemical staining for p53 and mismatch repair (MMR) proteins was done. All included cases showed different degrees of Cyclin D1 expression. Cyclin D1 expression was predominantly strong in 20 cases (44.4%). The density ranged from 1 to 90% and the H-score ranged from 1 to 270. Both H-score and density correlated significantly with MMR deficiency (p = 0.024 & p = 0.043 respectively) with different cut-offs (> 65 and >  20 respectively). Similarly, a predominant strong intensity correlated significantly with MMR deficiency (p = 0.023). Only Cyclin D1 density correlated significantly with FIGO grade (p = 0.036). At the assigned cut-off, H-score correlated significantly with the overall survival (p = 0.023). When predominantly moderately expressed, Cyclin D1 correlated significantly with recurrence free survival (p = 0.038). Cyclin D1 expression may predict MMR status and correlates with both overall survival and recurrence free survival in endometrial carcinoma.

Graves’ disease (GD) is the most common autoimmune disease characterized by the loss of immune tolerance induced by the activation of target antigens by the thyrotropin receptor (TSHR) autoantibody. Chemokines may be involved in the autoimmune inflammatory response in GD. In this study, we investigated the mechanism of chemokine expression in different tissues of GD hyperthyroid mice. Adenoviruses encoding the TSHR A subunit were employed to immunize female BALB/c mice to induce GD. HE-stained sections were used to observe the histopathological morphology, and RT-qPCR and immunohistochemistry were used to detect the expression levels of CCL2, CCL5 and ACKR1 in the tissues. ELISA was used to measure the levels of CCL2 and CCL5 in the serum of patients with GD. In HE-stained sections from hyperthyroid mice, the spleen showed hyperplasia of the red medulla, atrophy of the white medulla, hyperplasia of the trabecular veins, hyperplasia of the medullary region of the thymus, steatosis of the hepatocytes, atrophy of cardiomyocytes, atrophy of the kidneys, and necrosis of the adrenal glands and skeletal muscles. CCL5, CCL2 and ACKR1 expression levels were elevated in the spleen of GD hyperthyroid mice; CCL5 and CCL2 expression levels were elevated in thymus tissue; CCL2 and ACKR1 expression levels were elevated in thyroid tissue; and CCL5 expression was decreased in thyroid tissue. Chemokines were differentially expressed in other tissues. The pathological changes in various organs of GD hyperthyroid mice may provide a theoretical basis for studying the pathogenesis of GD complicating extrathyroidal diseases. Chemokines may play crucial roles in the immune mechanisms of GD and extrathyroidal diseases.

Targeting autophagy as a therapeutic approach against infections has gained significant attention nowadays. Amiodarone (AMD), the antiarrhythmic drug with autophagy-stimulating property, was used in this study, compared to Albendazole (ALB) (the commonly used drug) against experimental trichinellosis. Our in vivo study used two assessment tools for evaluating the autophagy process: quantitative analysis of local microtubule-associated protein 1 light chain 3 (LC3) autophagy protein marker, in addition to detecting autophagic compartments by transmission electron microscopy (TEM). AMD showed the most significant upregulation of local LC3 expression (15.54 ± 1.33 vs. 13.37 ± 2.03 with ALB, P < 0.005), besides identification of a wide range of autophagosomal cellular compartments, which most likely succeeded in controlling infection and inflammation, compared to few phagosomes and numerous macrophages seen in the ALB-treated group reflecting the lesser ability of the latter to stimulate the full autophagy process and suppress inflammation. In addition, signs of cellular repair were also noticed in TEM in the AMD-treated group, such as normal nuclear chromatin distribution with relatively normal mitochondrial allocation and regular muscle fibers. Autophagy detected in the ALB-treated group, despite being characterized by significant expression of LC3, seemed dysfunctional and inefficient in regulating inflammation and recovering normal cellular features. Our results revealed, for the first time, the exceptional potential of AMD as an autophagy modulator and regenerative supporter in treating trichinellosis. Thus, further investigations for the role of autophagy inducers as therapeutic options against other parasitic infections are recommended.

Despite evidence linking histone lactylation to tumorigenesis, its specific regulatory role in laryngeal squamous cell carcinoma (LSCC) is still not well defined. Histone H3K18 lactylation (H3K18la) levels in LSCC tissues were analyzed by immunohistochemistry (IHC) and western blot, showing significantly higher levels than non-tumor tissues. Treatment with the sodium oxamate (SO) effectively reduced H3K18la level, thereby suppressing LSCC cell proliferation and migration while inducing apoptosis. Mechanistically, H3K18la upregulated Runt-related transcription factor 2 (RUNX2) expression, which in turn activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway to promote aggressive LSCC phenotypes. Our findings demonstrate that H3K18la facilitates LSCC progression by enhancing malignant cellular behaviors, thereby offering potential therapeutic targets for LSCC intervention.

Asthma is a chronic respiratory disease characterized by airway hyper-responsiveness, inflammation, and pulmonary edema. Asthma may be triggered by allergens, certain medications, environmental exposure, respiratory infection, and physical exertion. Patients with asthma express higher levels of T helper cell 2 (Th2) cytokines i.e., IL-4 and IL-5. Estragole (EST), a phytochemical in essential oils, has shown anti-inflammatory and immunomodulatory effects. Current study was set out with the objectives to evaluate the anti-asthmatic effects of EST using various in vivo and in vitro experiments. Thirty-six (36) albino BALB/c mice were divided into six groups: Normal group (NG), OVA-induced asthma group (DG), Methylprednisolone group (MPG group, 15 mg/kg), Low, medium and high doses of EST (LDE: 10, 30 and 60 mg/kg, respectively). Mice were sensitized with 20 µg of OVA intraperitoneally and treated with EST during the challenge phase (21–27 days). Lung wet/dry ratio, total and differential leukocyte counts (TLC and DLC) in blood and Bronchoalveolar Lavage fluid (BALF) collections, histopathology (H&E, PAS), mRNA expressions of IL-4 and IL-5 in the lungs were analyzed, and molecular docking was performed. Airway inflammation was found ameliorated in EST treated groups as evident by reduction in TLC and DLC in both blood and BALF samples, and attenuation of infiltration of inflammatory cells in lungs. Furthermore, EST significantly reduced IL-4 and IL-5 mRNA expression levels in the lungs tissue and demonstrated notable binding affinity with IL-4 (− 4.5 kcal/mol), IL-5 (− 4.7 kcal/mol), and GATA-3 (− 5.3 kcal/mol). These docking results support the in vivo findings by suggesting a possible interaction of EST with key Th2 mediators, and their transcriptional regulator to suppress downstream airway inflammation, consistent with its observed anti-asthmatic effects. Estragole possesses anti-asthmatic property by attenuation of airway inflammation and pulmonary edema. Molecular docking, RT-qPCR, and histopathological evaluations suggesting that EST may attenuate allergic asthma via attenuation in Th2-mediated markers i.e., IL-4, IL-5, and GATA-3.

Osteosarcoma (OS) is a highly aggressive malignant bone tumor predominantly affecting adolescents and children. Extracellular vesicles (EVs) significantly contribute to the progression of osteosarcoma by promoting intercellular communication via the transportation of biomolecules and activation of signaling pathways. However, the specific role of tenascin-C (TNC) transmitted by EVs in osteosarcoma remains poorly understood. In this study, we reanalyzed mass spectrometry data of osteosarcoma-derived EV proteins from public databases. EVs were isolated and characterized using standard protocols. The expression levels of EV-derived TNC (EVs-TNC) were measured by western blot or enzyme-linked immunosorbent assay. Functional assays were used to elucidate the role of EVs-TNC in promoting OS malignancy. Transcriptome sequencing was conducted to identify downstream effectors of EVs-TNC. Our results revealed elevated circulating EVs-TNC concentrations in OS patients versus healthy controls. Furthermore, EVs-TNC derived from OS cell lines (SJSA-1 and 143B) were internalized by MG-63 cells, enhancing their proliferative and migratory capabilities. Mechanistically, EVs-TNC was found to regulate angiotensin II receptor type 1 (AGTR1) expression, suggesting a potential signaling pathway involved in OS progression. This study highlights the role of EVs-TNC in promoting OS proliferation and migration, indicating that targeting EVs-TNC may offer a novel treatment strategy for osteosarcoma.

Osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes such as articular cartilage degeneration and bone hyperplasia. Mitochondrial dysfunction in chondrocytes has been identified as a critical factor contributing to the progression of OA. Although Evodiamine (Evo) has been demonstrated effeicacy in inhibiting inflammatory responses and matrix degradation in OA chondrocytes, its effects and underlying mechanisms regarding mitochondrial dysfunction in these cells remain to be elucidated. IL-1β was utilized to stimulate chondrocytes in order to establish an in vitro OA model. Subsequently, the proliferation, lactate dehydrogenase (LDH) release, and apoptosis of chondrocytes were systematically evaluated. Mitochondrial function in chondrocytes was evaluated by quantifying of ATP content, ROS level, mitochondrial DNA (mtDNA) copy number, activities of mitochondrial respiratory chain Complexes I and III, as well as mitochondrial membrane potential change. Furthermore, the protein expression levels of the SIRT1/PGC-1α signaling pathway were examined, and an intervention involving the SIRT1 inhibitor EX527 was conducted to elucidate the potential mechanisms underlying the effects of Evo on chondrocytes. Evo treatment significantly elevated the proliferation activity of IL-1β-stimulated chondrocytes, inhibited LDH release and apoptosis, increased mtDNA copy number and ATP content, enhanced the enzymatic activities of Complexes I and III, and suppressed ROS production as well as mitochondrial membrane potential loss. Furthermore, Evo treatment activated the SIRT1/PGC-1α signaling pathway. However, the addition of the SIRT1 inhibitor EX-527 partially attenuated the protective effects of Evo against IL-1β-induced chondrocyte injury by exacerbating mitochondrial dysfunction. Evo promotes mitochondrial biosynthesis, reduces ROS production and improves mitochondrial function by activating SIRT1/PGC-1α pathway, thereby inhibiting IL-1β-induced chondrocyte injury.

Skin aging is a prominent manifestation of human aging, largely driven by oxidative stress and inflammation. D-limonene, a natural monoterpene, possesses strong antioxidant and anti-inflammatory properties that may help counteract these effects. This study aimed to explore the anti-aging and skin-rejuvenating potential of D-limonene in a mouse model of D-galactose-induced skin aging. 60 male mice were divided into 6 groups (n = 10). Group I served as the control. Group II received D-galactose (500 mg/kg) for 42 days to induce aging. Groups III and IV received vitamin C (100 mg/kg) either concurrently with D-galactose or after aging induction, respectively. Groups V and VI received D-limonene (100 mg/kg) either simultaneously with D-galactose or after induction. This design allowed comparison of protective versus therapeutic effects. Both concurrent and post-treatment with D-limonene substantially decreased pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and the oxidative stress marker MDA, while enhancing antioxidant components (SOD and GPx) and promoting the synthesis of collagen types I and III. Additionally, it improved skin thickness and histomorphological scores, restoring normal skin architecture. D-limonene exerts potent anti-aging and skin-rejuvenating effects by modulating oxidation and inflammatory markers, suggesting its potential as a preventive and curative anti-aging agent.

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Hyperammonemia is a key pathological feature of hepatic encephalopathy (HE), yet its associated protein glycosylation remains incompletely understood. Here, we used whole mouse brain tissues from a hyperammonemia mouse model and astrocytes to conduct a comprehensive analysis of glycosylation changes and the corresponding enzyme associated with ammonia. The upregulation of O-linked N-acetylglucosamine (O-GlcNAc), mediated by O-GlcNAc transferase, was identified as a response to ammonia stimulation in astrocytes through a mechanism independent of glutamine synthesis and NADPH oxidase. These findings identify O-GlcNAc as an ammonia-sensitive post-translational modification that is associated with hyperammonemia. This study provides new insights into the molecular mechanisms of HE and suggests the potential role of O-GlcNAc as a therapeutic target warranting further investigation.