Journal of Molecular Histology最新文献

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an important environmental pollutant that disturbs the immune balance of the maternal-fetal interface (MFI) and is also a common environmental factor for the formation of cleft palate (CP). Therefore, the purpose is to investigate whether TCDD can cause CP by disrupting the immune balance of the maternal-fetal interface. Fifteen C57BL/6J mice were randomly assigned to three groups: control group, TCDD group, and TCDD plus Freund’s complete adjuvant (FCA) (TCDD + FCA) group. Peripheral blood, placentas, and palatal tissues were collected for H&E, flow cytometry, and ELISA. In the TCDD group, the placental diameter, the number of placental labyrinth vessels, and the area of sponge layer cells were all significantly reduced. At embryonic day (E) 17.0, there was a significant decrease in T-helper 1 (Th1) and Th2 cells in the peripheral blood of pregnant mice. Additionally, the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4), particularly IL-4, were significantly decreased. However, after treatment with FCA, the distance between the palatal shelves was reduced, and the placental weight, the number of labyrinth vessels, and the area of the cavernous cells in the placenta also increased. The number of Th1 and Th2 cells significantly increased, returning to the levels observed in the control group, with a more pronounced increase in the number of Th2 cells. In conclusion, TCDD may induce CP by disrupting the homeostasis of the MFI. The precise mechanisms by which TCDD impacts the immune system at the MFI require further investigation.2,3,7,8-四氯二苯并-对二恶英 （TCDD） 是一种重要的环境污染物，会扰乱母胎界面 （MFI） 的免疫平衡，也是形成腭裂 （CP） 的常见环境因素。因此，目的是研究 TCDD 是否可以通过破坏母胎界面的免疫平衡来引起 CP。将 15 只 C57BL/6J 小鼠随机分为 3 组：对照组、TCDD 组和 TCDD 加弗氏完全佐剂 （FCA） （TCDD + FCA） 组。收集外周血、胎盘和腭组织用于 H&E、流式细胞术和 ELISA。TCDD 组胎盘直径、胎盘迷路血管数量和海绵层细胞面积均显著减少。在胚胎第 17.0 天 （E） 时，妊娠小鼠外周血中的 T 辅助细胞 1 （Th1） 和 Th2 细胞显著减少。此外，干扰素-γ （IFN-γ） 和白细胞介素-4 （IL-4），特别是 IL-4 的水平显着降低。然而，用 FCA 处理后，腭架之间的距离减小，胎盘重量、迷路血管的数量和胎盘中海绵状细胞的面积也增加。Th1 和 Th2 细胞的数量显著增加，恢复到对照组观察到的水平，Th2 细胞的数量增加更明显。总之，TCDD 可能通过破坏 MFI 的稳态来诱导 CP。TCDD 影响 MFI 免疫系统的确切机制需要进一步研究。

It is crucial to investigate new anti-diabetic agents and therapeutic approaches targeting molecules in potential signaling pathways for the treatment of Type 2 diabetes mellitus (T2DM). The objective of the study was to investigate the total phenolic content, antioxidant capacity, α-glucosidase, and α-amylase inhibitory activities of Bolanthus turcicus (B. turcicus), as well as their cytotoxic, anti-adipogenic, anti-diabetic, apoptotic, and anti-migration potential on adipocytes. B. turcicus samples were extracted with methanol (MeOH), ethyl acetate (EA) and aqueous (Aq) solvents. The MeOH extract had the highest phenolic content (81.14 mg GAE/g), followed by EA (74.93 mg GAE/g) and Aq (51.09 mg GAE/g). All extracts exhibited dose-dependent increases in α-glycosidase and α-amylase inhibitory activity. B. turcicus extracts showed cytotoxic effect on adipocytes with IC₅₀ values of MeOH (141.0 µg/mL) < Aq (155.3 µg/mL) < EA (199.5 µg/mL). Furthermore, B. turcicus extracts reduced lipid droplet formation and adipocyte diameter size. All extracts altered cell morphology to resemble fibroblasts. B. turcicus extracts exhibited anti-migratory effect delaying wound healing for up to 96 h. The B. turcicus extracts showed a pro-apoptotic effects on adipocytes by increasing Caspase-3 enzyme activity and the population of DAPI-positive cell with apoptotic nuclear-morphology. B. turcicus extracts upregulated the expression of the Glut-4 gene at the mRNA, protein and intracellular level in adipocytes. In conclusion, our findings indicate that B. turcicus not only exhibits strong antioxidant properties and enzyme inhibitory activities but also exerts significant anti-adipogenic and pro-apoptotic effects in adipocytes, thereby providing a comprehensive mechanism through which it may contribute to the management of T2DM. These effects highlight the potential of B. turcicus as a therapeutic agent for improving glucose homeostasis and insulin sensitivity.

Sodium valproate– a salt of valproic acid (VPA), is an anticonvulsant used in the treatment of epilepsy and a range of psychiatric conditions that include panic attacks, anxiety, post-traumatic stress, migraine and bipolar disorder etc. VPA can cause direct damage to many tissues due to accumulation of toxic metabolites. Nowadays, phytochemicals are amongst the best options for the treatment of diseases. Moringa oleifera is a popular plant in the tropics owing to its numerous pharmacological and phytochemical properties such as antiproliferative, hepatoprotective, anti-inflammatory, and cardioprotective effects. In the present study, the protective effects of Moringa ethanol extract on oxidative lung damage caused by VPA was assessed biochemically and histologically. Sprague Dawley female rats were divided into 4 groups: Control, Moringa extract (M), sodium valproate (V), and sodium valproate + Moringa extract (V + M). Doses of sodium valproate and Moringa extract (dissolved in physiological saline) were given at 500 mg/kg b.w. and 300 mg/kg b.w. for 15 days, respectively. The rats were sacrificed on the 16th day, lung tissues collected biochemical parameters (glutathione level, antioxidant enzyme activities, oxidative stress biomarker and inflammatory proteins) and histopathological findings obtained from the study indicated increased damage in lung tissue of the valproate administered group. The damage was prevented/decreased upon administration of Moringa to the valproate rats. The present findings revealed that Moringa extract had a protective and therapeutic effect against VPA induced lung damage. Moringa extract demonstrated an ameliorative effect on histopathological and biochemical parameters in valproate induced lung damage.

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Chronic oxidative stress (COS) is related to the pathophysiology of the trabecular meshwork (TM) in glaucoma. MicroRNAs (miRNAs) have a key role in the oxidative stress-mediated glaucoma. This work investigated the function of miR-126-5p in human trabecular meshwork cells (TMCs) under chronic oxidative stress (COS). The miR-126-5p inhibitor was transfected into TMCs to assess the function of miR-126-5p. The targets of miR-126-5p were predicted by bioinformatic analysis. A luciferase assay was applied to test the relationship between miR-126-5p and its target. Cell proliferation was assessed using MTT. Flow cytometry and TUNEL were used for the assessment of apoptosis. We found that the miR-126-5p level was elevated in TMCs exposed to COS. MiR-126-5p inhibitor markedly promoted TMC proliferation and inhibited the increases in apoptosis and extracellular matrix (ECM) proteins induced by COS. Heat shock protein B8 (HSPB8) was identified to be targeted by miR-126-5p. MiR-126-5p inhibitor restored the expression level of HSPB8 in TMCs under COS. Additionally, miR-126-5p depletion activated PI3K/AKT signaling in TMCs by upregulating HSPB8. HSPB8 downregulation or LY294002 treatment prevented the effects mediated by miR-126-5p inhibition on apoptosis and ECM in COS-treated TMCs. Overall, silencing miR-126-5p protects TMCs against COS-induced injury by upregulating HSPB8 to activate PI3K/AKT signaling.

Embryonic development during the preimplantation stages is highly sensitive and critically dependent on the reception of signaling cues. The precise coordination of diverse pathways and signaling factors is essential for successful embryonic progression. Even minor disruptions in these factors can result in physiological dysfunction, fetal malformations, or embryonic arrest. This issue is particularly evident in assisted reproductive technologies, such as in vitro fertilization, where embryonic arrest is frequently observed. A detailed understanding of these pathways enhances insight into the fundamental mechanisms underlying cellular processes and their contributions to embryonic development. The significance of elucidating signaling pathways and their regulatory factors in preimplantation development cannot be overstated. The application of this knowledge in laboratory settings has the potential to support strategies for modeling developmental stages and diseases, drug screening, therapeutic discovery, and reducing embryonic arrest. Furthermore, using various factors, small molecules, and pharmacological agents can enable the development or optimization of culture media for enhanced embryonic viability. While numerous pathways influence preimplantation development, this study examines several critical signaling pathways in this contex.

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Recurrent pregnancy loss (RPL) is the occurrence of two or more consecutive miscarriages before 20 weeks of gestation. Recent research has increasingly focused on the role of oxidative stress in RPL, providing insights into its underlying mechanisms and potential therapeutic targets. Oxidative stress arises from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, leading to cellular damage and inflammation. Oxidative stress has been implicated in disrupting placental blood flow, inducing apoptosis in fetal and placental cells, and exacerbating inflammatory responses, all of which can contribute to pregnancy loss. Elevated levels of ROS have been associated with compromised placental function, impaired fetal development, and increased risk of RPL. Additionally, oxidative stress can modulate maternal immune responses, potentially leading to immune-related pregnancy complications. This review synthesizes current evidence on the mechanisms by which oxidative stress contributes to RPL and highlights emerging research on potential interventions, including antioxidant therapies and lifestyle modifications. Understanding these mechanisms is crucial for developing effective preventive and therapeutic strategies to reduce the risk of RPL and improve pregnancy outcomes. Future research should focus on elucidating the specific pathways involved and exploring novel treatments aimed at mitigating oxidative damage during pregnancy.

A poorer prognosis is thought to be associated with “double expressor lymphomas,” which are a subtype of diffuse large B cell lymphomas (DLBCL) that co-express MYC and BCL2. While the role of ubiquitin-specific peptidase 37 (USP37) in lung cancer, where it mediates the deubiquitination and stabilization of c-myc, has been well-documented, its involvement in DLBCL remains unexplored. The use of RT-PCR, immunohistochemistry, or WB test allowed for the detection of elevated USP37 in DLBCL tissues and cells. In order to understand the function of USP37 in DLBCL, keloid DLBCL cells were transfected with si-USP37 using Lipofectamine 3000. When tested on DLBCL cells, USP37 increased cell proliferation and inhibited cell cycle progression. USP37 controls the process of deubiquitination to stabilise c-myc proteins. The overexpression of c-Myc facilitated cell proliferation and prevented the cell cycle of DLBCL cells stimulated by si-USP37, which should be taken into consideration. Furthermore, USP37 depletion consistently hinders the development of tumour xenografts in mouse models. Overexpressing c-myc, however, may partially counteract this impact. The data show that USP37 may be a potential therapeutic target for DLBCL, and that it may enhance the course of the disease by deubiquitinating c-myc via direct interactions with c-myc.

The purpose of this study was to explore the inhibitory effect of andrographolide on the expression of key regulatory genes involved in the biofilm formation of Staphylococcus epidermidis (SE). Taking the film-producing strain Staphylococcus epidermidis SE1457 as the research object, the effect of andrographolide on the formation of Staphylococcus epidermidis biofilms was analyzed via crystal violet staining, and biofilm models of SE adhesion, aggregation and maturity were established in vitro. RT‒PCR was used to detect the effects of the expression of icaA-, atlE-, aap- and luxS-related genes of andrographolide on biofilm formation in SE. Congo red qualitative test to evaluate the ability of andrographolide to inhibit biofilm formation of Staphylococcus epidermidis. Compared with that of the control group, the light absorption value of the low- and high-concentration andrographolide groups was significantly lower, and the light absorption value of the high-concentration andrographolide group was significantly lower than that of the low-concentration andrographolide group. The levels of key genes involved in the adhesion, aggregation and maturation of icaA, atlE, aap and luxS in group C were greater than those in group B. The biofilm-forming ability of SE in group A was strong, and the colonies were obviously black. The colony in the direction of the arrow in group B was red, and the SE biofilm was inhibited. Most of the colonies in group C were red. SE biofilms were significantly inhibited. Andrographolide inhibits SE biofilm formation, and its mechanism may involve inhibition of the expression of the related genes icaA, atlE, aap and luxS.

Ki-67 is a histological marker indicating cancer aggressiveness, while tryptophan (TRP) depletion modulates immune responses, including tumor aggressiveness. The study evaluates Ki-67's predictive value in relation to plasma TRP levels in invasive ductal carcinoma of breast cancer, aiming to improve understanding of tumor characteristics and clinical behavior. A study involving 165 women, measured plasma TRP levels and Ki-67 and analyzed their relationship with tumor aggressiveness markers using statistical analyses and predictive models. Our study highlighted a significant correlation between decreased plasma levels of TRP and a high mitotic index, measured by the Ki-67 marker (Pearson correlation coefficient r = − 0.402; p = 0.011). Tryptophan levels below 40 µmol/L were associated with a Ki-67 level above 15%, suggesting more active tumor growth in patients. Additionally, several risk factors for BC were identified within the studied population. The demographic and clinical characteristics of the participants include an average age of 63 years, plasma glucose levels above 1.2 g/L, and plasma TRP levels below 40 µmol/L, which are associated with an increased risk of BC. Furthermore, various polynomial logistic regression models indicate that TRP levels may be predicted based on Ki-67 expression, providing a promising approach to refine prognostic assessments. The study showed a correlation between low levels of tryptophan (TRP) and a high Ki-67 mitotic index in breast cancer patients, particularly in invasive ductal carcinoma, which is strongly linked to the aggressiveness of the disease. The integration of these markers into routine practice remains a technical and economic challenge.

Aging is a worldwide socioeconomic burden. Cerebellar aging is an enigma contributing to many behavioral aging disorders, hence is its hindering by prophylactic measurements is a crucial geriatric research target. Red dragon fruit (RDF) is a tropical fruit with antioxidant, anti-inflammatory and anti-apoptotic properties. This study aimed to determine the protective effect of RDF extract against cerebellar aging. Thirty-two male albino rats were randomly allocated into 4 groups: Control, RDF, aged and RDF-aged groups. Aged group revealed structural distortion affecting cerebellar layers including a significant (P < 0.05) decrease in Purkinje cells number and decrease in granular cell layer thickness by comparison to the control and RDF groups. Additionally, distorted capillary endothelium, and defective myelination were noticed. Interestingly, cerebellar active caspase-3, iNOS, MDA and 3-NT and serum TNF-α levels significantly increased with aging by comparison to the control and RDF groups (all P < 0.05). Biochemical analysis revealed a significant (P < 0.05) decrease in cerebellar SOD and serum GSH levels in aged rats. RDF extract remarkably ameliorated most of the neuronal degenerative changes with a significant (P < 0.05) increase in Purkinje cells numbers, and granular cell layer thickness by comparison to the aged group. Furthermore, it resulted in a significant (P < 0.05) decrease in cerebellum expression of active caspase-3, iNOS, MDA, 3-NT, and serum TNF-α levels associated with a significant (P < 0.05) increase in cerebellar SOD and serum GSH levels by comparison to the aged group. To the best of our knowledge this is the first study showing a neuroprotective effect for RDF against cerebellar aging. RDF might be effective in attenuation of age-induced cerebellar degenerative changes through its anti-apoptotic, antioxidant and anti-inflammatory effects.