Journal of Molecular Histology最新文献

Sevoflurane is extensively employed as an inhalation anesthetic in medical practices, due to its promising pharmacokinetics. Conversely, the data regarding effects of prolonged exposure to trace amounts of sevoflurane on the female reproductive system is obscure. Therefore, this study aimed to investigate the reproductive toxicity and underlying mechanism of long-term sevoflurane inhalation in female rats. A total 60 SPF grade SD female rats were randomly alienated into four equal groups as control group (A), 50 ppm sevoflurane group (B), 150 ppm sevoflurane group (C), and 300 ppm sevoflurane groups (D). Ovaries and uterine organs were collected for gross as well as histopathological analysis, western blotting, and immuno-histochemistry evaluation. Results revealed that pregnancy rate, number of fetuses (fetal mice) and general body weight of group B, C, and D were substantially lower (P < 0.05), while were compared with control. On the contrary, estrous period in groups B, C, D was shortened noticeably (P < 0.05), and estrus interval and cycle were significantly longer (P < 0.05). In fact, the ovarian and uterine coefficients of group B, C and D were significantly reduced as compared with control. However, ovarian and uterine histomorphology remained normal in control group, while obvious pathological alterations were detected in groups B, C, and D. Although, the expression of SOD protein in the ovarian and uterine tissues of groups B, C, and D was significantly reduced (P < 0.05), in contrast to group A. However, the MDA protein expression increased significantly (P < 0.05) as compared with group A. While expression of apoptosis-related genes (Bcl2 and Bax) and humoral immunity related genes (IL-6, IL-10 and TNF-α) showed highest elevation in groups exposure with sevoflurane (p < 0.001) in comparison to control. Conclusively, long-term inhalation of trace amounts of sevoflurane is toxic to female reproductive system and can severely affect reproductive organs and fertility by induction of oxidative stress and apoptosis.

Graphical abstract

Moringa oleifera (M. oleifera) is a popular medicinal plant that has become a wide research area in recent years due to its detected biological effects and its bioactive compounds. Valproic acid (VPA) is a medication used in the treatment of epilepsy and bipolar disorder and high doses or prolonged use of VPA can result in oxidative stress in cells. Since M. oleifera has high biological activities and contains many bioactive compounds, it is necessary to understand whether it plays a role in reducing oxidative damage, especially that caused VPA. The relationship between VPA and tongue tissue needs to be investigated, since VPA has negative effects on oral health and it is known that tongue tissue plays an important role in the continuity of oral health. In the present study, 3.0–3.5 month-old female Sprague Dawley rats (160–250 g) were divided into four groups (Control, Moringa, VPA, VPA + M), and VPA was administered via gavage. The aim was to understand the protective/preventive effects of ethanolic M. oleifera leaves extract against oxidative stress through biochemical parameters. Additionally, molecular docking studies were conducted on niazicin-A, niazimin-A, and niazimin-B found in M. oleifera leaves based on in vivo results. The results indicate that M. oleifera extract treats oxidative damage to the tongue tissue, and niazimin-A and niazimin-B particularly show high binding affinities to myeloperoxidase (MPO) and lactate dehydrogenase (LDH) enzymes. Further studies may suggest that the use of M. oleifera leaves extract with VPA could prevent potential negative effects on tongue tissue.

Arthritis is characterized by the progressive degeneration of articular cartilage, and the avascular nature of cartilage limits its capacity for self-repair. Stem cells are considered a promising treatment option due to their multipotent differentiation potential. The aim of this work was to investigate the structural changes in the hyaline articular cartilage of the knee joint in a model of arthritis induced by complete Freund’s adjuvant, and to assess intra-articular injection of bone marrow mesenchymal stem cells (BM-MSCs) through both histological and immunohistochemical study. Adult male albino rats were divided into four groups: group 0 (donor group), group I (control group), group II (arthritis group) and group III (BM-MSCs treated arthritis group). Samples were collected 2, 6 and 10 weeks after the onset of the experiment. Sections were stained with; hematoxylin and eosin, Safranin O fast green stain, Masson’s trichrome stain and anti-MMP9 antibody. In Group II (arthritis group), the articular cartilage showed signs of degeneration, including chondrocyte extensive proliferation, fibrillations, fissuring, and denudation, with fibrous tissue covering the exposed surface. There was a significant decrease in cartilage thickness, collagen content, and proteoglycan levels. The integrated density of MMP9 in the cartilage was significantly increased compared to Group I (control group). In contrast, Group III (BM-MSCs-treated arthritis group) exhibited a continuous cartilage surface with no cracks or fissures. There was a significant increase in cartilage thickness, collagen content, and proteoglycan levels, while the integrated density of MMP9 was significantly decreased compared to Group II (arthritis group).

Increasing incidences of fatty liver in humans and animals worldwide is the leading cause of liver related morbidities. Currently, in the face of the growing global increase in fatty liver, and the necessity to explore new factors significantly affecting it, aquaporins (AQPs) have become the focus of interest for many researchers. AQPs are membrane integral proteins involved in the transport of water, glycerol and other small solutes. These are expressed in all tissues and play multiple roles under normal and pathophysiological conditions. Despite ongoing advancements in understanding the involvement of aquaporins in metabolic processes, there remains a notable lack of knowledge concerning cellular and subcellular localization of the AQPs in bovine tissues and organs. Understanding this could provide a new therapeutic target for metabolic syndromes such as fatty liver disease in bovine. In this study, AQPs in bovine liver, adipose tissue and gall bladder are examined using immunohistochemistry. AQP9 immunoreactivity is predominantly detected at the sinusoidal surfaces of hepatocytes. AQP8 is mostly intracellular and localized to the central vein and sinusoid, whereas AQP7 is found around the portal vein. Notably, AQP3 is observed in the bovine gall bladder and adipose tissue but not in the liver. In adipose tissue, AQP7 is also detected in the cytoplasmic membranes of adipocytes. AQPs in liver and adipose tissue were also studied using the western blotting technique. Higher AQP9 and AQP3 expression is observed in the liver and adipose tissue, respectively, indicating they are the dominant aquaporins in these tissues. This suggests they could be potential therapeutic targets for treating fatty liver disease and other metabolic disorders in bovine.

Preeclampsia (PE) is a form of hypertension that manifests in the later stages of pregnancy. Since Kaempferol (Ka) has remedial potential hence this research was conducted to examine its therapeutic effect on Preeclampsia rats by regulating Wingless-related integration site/β-catenin (Wnt/B-catenin) pathway. To achieve this, thirty-two SD female rats were randomly allocated into four groups: control, preeclampsia (PE, LPS, 1 mg/kg), preeclampsia with kaempferol (PE + Ka), and preeclampsia with Dickkopf − 1 (DKK-1) and kaempferol (PE + DKK-1 + Ka). Rats in the PE + Ka and PE + DKK-1 + Ka groups received intraperitoneal injections at 50 mg/kg/d of kaempferol, whereas the PE + DKK-1 + Ka group was administered with 60 µg/kg/d of recombinant rat DKK-1 protein, an inhibitor of the Wnt/β-catenin signaling pathway. Our findings revealed that systolic blood pressure (SBP) in the PE + Ka group was significantly reduced in comparison to PE group (P < 0.05). The urine albumin levels in the PE + Ka group decreased noticeably (P < 0.05), whereas serum concentrations of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) in the PE + Ka group were reduced (P < 0.05) in comparison to PE group. Although PE + Ka group exhibited elevated levels of superoxide dismutases (SOD), glutathione (GSH), and catalase (CAT) in placental tissue relative to the PE group, whilst levels of malondialdehyde (MDA), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and serum glutamic-oxaloacetic transaminase (SGOT) considerably decreased (P < 0.05). Comparatively mRNA levels of Wnt1 and β-catenin in the PE + Ka group were elevated, whereas mRNA level of DKK-1 was diminished (P < 0.05). Administration of DKK-1 counteracted kaempferol effects on these parameters in Preeclampsia rats (P < 0.05). Devastatingly, ovarian and kidney histomorphology in the PE group exhibited significant degenerative alterations, whereas kaempferol groups demonstrated normal histomorphology in comparison to the PE group. Conclusively, Kaempferol can significantly lower systolic blood pressure and urine albumin in PE female rats while mitigating excessive oxidative stress. The therapeutic efficacy of kaempferol on Preeclampsia may be mediatated via Wnt/β-catenin signaling pathway.

Background

Breast cancer (BC) poses a significant global health challenge, with chemotherapy resistance, especially to docetaxel, remaining a major obstacle in effective treatment. The molecular mechanisms underlying this resistance are critical for developing targeted therapeutic strategies.

Objective

This study aims to explore the role of dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2), a member of the DYRK family, in docetaxel resistance in breast cancer cells and investigate its impact on cellular responses, including drug sensitivity and migration. Additionally, potential interactions between DYRK2 and Twist1, associated with epithelial-mesenchymal transition (EMT) and drug resistance, are explored. Methods: Docetaxel-resistant breast cancer cells were induced, and the expression levels of DYRK2, Twist1, and related genes were evaluated using real-time PCR and Western blotting. Lentivirus-mediated DYRK2 overexpression was employed to assess its effect on drug sensitivity, migratory ability, and Twist1 expression. The relationship between DYRK2 and Twist1 was examined, focusing on Twist1 ubiquitination. The impact of Twist1 on chemotherapy resistance and its binding to the Glutathione S-transferase Pi 1 (GSTP1) promoter were also investigated.

Results

Docetaxel-resistant cells exhibited down-regulated DYRK2 and up-regulated Twist1 expression. DYRK2 overexpression reversed drug resistance, decreased migration, and attenuated Twist1 and GST-π expression. DYRK2 was found to suppress Twist1 expression through ubiquitination, supported by decreased Twist1 phosphorylation and increased ubiquitination after DYRK2 overexpression. Twist1 overexpression counteracted DYRK2-induced drug sensitivity enhancement, promoting GST-π expression, EMT, migration, and proliferation. Twist1 was shown to bind to the GSTP1 promoter, enhancing its transcription. In vivo experiments confirmed DYRK2’s ability to suppress chemoresistance in breast cancer cells.

Conclusion

DYRK2 plays a pivotal role in overcoming docetaxel resistance in breast cancer cells by suppressing Twist1 expression through ubiquitination, impacting downstream signaling and cellular responses. This study provides valuable insights for developing targeted therapies to improve breast cancer treatment outcomes.

GATA zinc finger domain containing 1 (GATAD1) is an as-yet uncharacterized zinc finger domain protein, which was initially identified as a histone 3 trimethylated at lysine 4 (H3K4me3) interactor. A recessive mutation in GATAD1 is associated with adult-onset dilated cardiomyopathy and heart failure, suggesting that GATAD1 is critical for maintaining normal cardiac structure and function. However, little is known as to the specific role of GATAD1 in cardiomyocytes. A mammalian Gatad1 knockout model has yet to be generated for investigating its specific role in the heart. To address this, we generated a Gatad1 cardiomyocyte-specific knockout (cKO) mouse model. Gatad1 cKO mutants exhibited normal cardiac function during the aging process up to 18 months of age. Unlike the abnormal nuclei shape observed in patients carrying GATAD1 mutations, the nuclei shape of cardiomyocytes remained unaffected by the loss of Gatad1. Furthermore, Gatad1 cKO mice responded normally to pressure overload induced by transverse aortic constriction (TAC) surgery. Together, these observations suggest that deletion of Gatad1 in cardiomyocytes does not induce cardiomyopathy during aging or affect the response to pressure overload stress in mice.

Women experience several systemic changes over all stages of life, many due to hormonal fluctuations. The sensation of dry mouth is the most common oral clinical symptom in women from climacteric period onwards, suggesting that sex hormones are important in maintaining salivary glands and oral homeostasis. Although the oral cavity is not conventional considered a target tissue for oestrogen, the extent to which salivary glands morphology and function are impacted by ageing and hormonal variations remain unknown. Due to the clinical demand for understanding oral changes related to the ageing process, this study aimed to portray the glandular morphological aspects in female during the different stages of life. To achieve this, 85 post-mortem specimens of labial minor salivary glands were obtained from females; they were distributed into three groups: group I (reproductive phase: up to 44 years, n = 18); group II (climateric phase: 45–55 years, n = 21) and group III (post-menopausal phase: over 56 years, n = 46). The most significant changes observed included degenerative parenchymal aspects including the replacement of parenchymal structures by fibrous tissue, inflammatory infiltrate as well as vascular and endothelial changes. Ageing was associated with acinar serous metaplasia (p = 0.011), acinar fibrosis (p = 0.042) and ductal ectasia (p = 0.003). The process of acinar atrophy was observed in all groups, with an increase in severity in group III. These degenerative aspects appear to be age-dependent.

Background

Among couples, male factors account for approximately 50% of infertility cases, with nonobstructive azoospermia (NOA) representing one of the most clinically common and severe categories of male infertility, affecting approximately 10–15% of patients. Currently, L-carnitine is clinically used to improve spermatogenesis by regulating Sertoli cell function. Multiple clinical trials have described the efficacy of L-carnitine in treating NOA. Notably, Sertoli cells rely on organic carnitine transporter 2 (OCTN2) for carnitine transport. However, it remains unknown whether OCTN2 expression is involved in the pathological process of NOA.

Objective

To investigate the expression and function of OCTN2 in Sertoli cells from patients with NOA.

Materials and methods

Ten testicular tissue samples were collected, including five from a healthy group and five from a group of patients with NOA. Immunohistochemistry and immunofluorescence were used to detect the expression of OCTN2 in testicular tissue. Additionally, an Octn2-KO TM4 cell line (a mouse testicular Sertoli cell line) was constructed to explore the function of OCTN2 expression in Sertoli cells through transcriptomic sequencing, cell proliferation experiments, metabolomic analysis, and Western blot analysis.

Results

Compared with those of the healthy group, the immunohistochemistry results revealed a significant decrease in OCTN2 expression in the Sertoli cells of the NOA group. Further investigation through cell proliferation experiments revealed a reduction in the proliferative capacity of the Octn2-KO TM4 cell line. Transcriptomic sequencing and metabolomic data analysis revealed a decrease in autophagy in the Octn2-KO TM4 cell line. Western blot analysis subsequently verified the expression levels of autophagy-related proteins.

Conclusion

In the Sertoli cells of NOA patients, decreased OCTN2 protein expression leads to decreased cell proliferation and autophagy abnormalities, which may play a crucial role in the spermatogenic dysfunction observed in NOA patients.