Histology and histopathology Vol.39,nº11 (2024)

Permanent URI for this collection

http://hdl.handle.net/10201/179879

Browse

Now showing 1 - 12 of 12

Open Access
Polydatin protects against articular cartilage degeneration by regulating autophagy mediated by the AMPK/mTOR signaling pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Ye, Zhengcong; Lin, Jian; He, Chun; Yu, Pengzheng; Cao, Guoping; Shen, Qinrong; Wang, Canfeng
Background. Knee osteoarthritis (KOA) is one of the leading causes of disability. Polydatin has a potential effect on KOA treatment but the therapeutic mechanism is not clear. This study aims to investigate the therapeutic action of polydatin in KOA and its mechanism in activating autophagy via the AMP-activated protein kinase (AMPK)/mTOR signaling pathway. Methods. After a KOA rat model was established by anterior cruciate ligament transection surgery, model rats were treated with polydatin 40 mg/kg for 30 days. Subsequently, cartilage tissues were collected, and hematoxylin-eosin (HE), Safranin-O, and TUNEL staining, and western blotting were performed to evaluate the pathological damage and autophagy-related protein expression. Then, human chondrocyte C28/I2 cells were stimulated with lipopolysaccharide (LPS), and the effects of polydatin on C28/I2 cell viability, apoptosis, and autophagy-related protein expression were detected by MTT, Flow Cytometry, and western blot. In addition, an AMPK inhibitor (Dorsomorphin 2HCl) was used to probe the cell proliferation and apoptosis of polydatin-administered C28/I2 cells. Results. Polydatin ameliorated the pathological damage in rat cartilage tissues and inhibited cell apoptosis in KOA rats. Meanwhile, in C28/I2 cells, polydatin promoted viability and reduced apoptosis. In addition, the protein expression of collagen II, LC3II/LC3I, Beclin-1, and p-AMPK/AMPK were upregulated, and p62 and p-mTOR/mTOR were downregulated by polydatin treatment. Interestingly, relative results showed that the protective effect of polydatin in LPS-stimulated-C28/I2 cells was blocked by the AMPK/mTOR inhibitor, dorsomorphin 2HCl. Conclusion. Our research showed that polydatin reduced apoptosis and activated autophagy both in vivo and in vitro by the AMPK/mTOR signaling pathway to protect against KOA, which provided the basis for further investigation into the potential therapeutic impact of polydatin on KOA.
Open Access
NCAPD3 is a prognostic biomarker and is correlated with immune infiltrates in glioma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Qu, Linzhuo; Che, Huiying; Zhao, Jingyu; Lu, Xin; Ren, Zijun; Wu, Yu; Liu, Qian; Guan, Hongjian
Non-SMC Condensin II Complex Subunit D3 (NCAPD3) has been linked with the genesis and progression of multiple human cancers. Nevertheless, the scientific value and molecular process of NCAPD3 in glioma remain unclear. We explored the level of NCAPD3 expression in pan-cancer by multiple online databases. And we focused on the level and prognostic value of NCAPD3 expression in glioma by immuno-histochemistry (IHC) and survival analysis. Meanwhile, we verified the relationship between NCAPD3, biological function and immune infiltration in glioma by Linkedomics and SangerBox databases. The expression of NCAPD3 was increased in a variety of cancers, including glioma. Its high expression was strongly related to WHO grade (P=0.002) and programmed cell death ligand 1 (PD-L1) expression of glioma (P=0.001). Patients with a high level of NCAPD3 expression had a lower overall survival (OS) in glioma than patients with a low level of NCAPD3 expression. Multivariate statistical analyses showed NCAPD3 expression (P=0.040), WHO grade P<0.001), 1p/19q codeletion (P<0.001), recurrence (P<0.001), age (P=0.023), and chemotherapy status (P=0.001) were meaningful independent prognostic factors in patients with glioma. Furthermore, bioinformatics analysis proved that NCAPD3 has been linked to immune infiltration in glioma. High level of NCAPD3 expression may serve as a promising prognostic biomarker and correlate with dendritic cell infiltration, representing a potential immunotherapy target in glioma
Open Access
The diverse functions of DYRK2 in response to cellular stress
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Kawamura, Akira; Yoshida, Saishu; Yoshida, Kiyotsugu
To maintain microenvironmental and cellular homeostasis, cells respond to multiple stresses by activating characteristic cellular mechanisms consisting of receptors, signal transducers, and effectors. Dysfunction of these mechanisms can trigger multiple human diseases as well as cancers. Dual-specificity tyrosine-regulated kinases (DYRKs) are members of the CMGC group and are evolutionarily conserved from yeast to mammals. Previous studies revealed that DYRK2 has important roles in the regulation of the cell cycle and survival in cancer cells. On the other hand, recent studies show that DYRK2 also exhibits significant functions in multiple cellular stress responses and in maintaining cellular homeostasis. Hence, the further elucidation of mechanisms underlying DYRK2’s diverse responses to various stresses helps to promote the advancement of innovative clinical therapies and pharmacological drugs. This review summarizes the molecular mechanisms of DYRK2, particularly focusing on cellular stress responses.
Open Access
Blood-brain barrier disruption following brain injury: Implications for clinical practice
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Bai, Ruojing; Ge, Xintong
The blood-brain barrier (BBB) plays a critical role in regulating the exchange of substances between peripheral blood and the central nervous system and in maintaining the stability of the neurovascular unit in neurological diseases. To guide clinical treatment and basic research on BBB protection following brain injury, this manuscript reviews how BBB disruption develops and influences neural recovery after stroke and traumatic brain injury (TBI). By summarizing the pathological mechanisms of BBB damage, we underscore the critical role of promoting BBB repair in managing brain injury. We also emphasize the potential for personalized and precise therapeutic strategies and the need for continued research and innovation. From this, broadening insights into the mechanisms of BBB disruption and repair could pave the way for breakthroughs in the treatment of brain injury-related diseases.
Open Access
Prevention of colon enlargement by TNF-α antagonist in a streptozotocin-induced diabetic rat model
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Sholikah, Tri Agusti; Septyaningtrias, Dian Eurike; Sumiwi, Yustina Andwi Ari; Muthmainah, M.; Susilowati, Rina
Summary. Purpose. We investigated the effect of tumor necrosis factor (TNF)-α antagonist on the structure and function of the streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat colon. Methods. Thirty rats were divided into normal control (NC), diabetic control (DC), and diabetic etanercept (DE) groups. The DE group was injected with etanercept twice a week. Blood glucose, body weight, fecal pellet, colonic transit time, and plasma TNF-α were measured. The colon was dissected out, followed by weight and length measurements. Toluidine blue and Verhoeff’s staining, immunohistochemistry for TNF-α, RAGE, iNOS, arginase, and western blot for RAGE were performed on the colonic tissue. Results. Administration of TNF-α antagonist had no significant effect on the body weight and blood glucose level of the diabetic groups. However, the DE group had a shorter and lighter colon and less coarse and less dense collagen fibers in the submucosal layer than the DC group. Weaker immunoreactivity of TNF-α, RAGE, iNOS, and arginase I was observed in colon tissue sections of the DE groups compared with the DC group. Although the etanercept effect on colonic function was not significantly different, the preventive effect size of etanercept on colon remodeling was considerably large, as shown by calculated-Cohen’s d>0.8. Conclusions. TNF-α signaling in the colonic tissue of diabetic rats has a strong effect on tissue remodeling, leading to colon enlargement. TNF-α antagonists may be beneficial in preventing diabetic-related pathology in the colon in combination with anti-diabetic drugs
Open Access
Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Lin, Ling; Chen, Zhen; Huang, Ping; Chen, Wei; Zou, Zhefei; Zheng, Yexian; He, Chang; Gu, Xiang; Yu, Dan; Zhang, Qiong
Background. Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells. Methods. LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling. Results. The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment. Conclusion. Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.
Open Access
Establishment of human acute monocytic leukemia model with systemic infiltration in NPG mice
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Xu, Jing; Wu, Qiong; Rao, Yanfei; Li, Zhenjiang; He, Wenfeng; Sun, Wanlei; Zheng, Jifu; Wang, Qingming; Tang, Aiping
A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immuno-suppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry. The median survival of mice in groups A and B were 33.0 and 30.0 days, respectively. Blast cells in peripheral blood appeared on day 14 in group B, and on day 21 in group A. In addition, SHI-1 cell specific MLL-AF6 mRNA was detected in both spleen and bone marrow on day 14 post-inoculation. 21 days after inoculation, we observed human CD45+CD33+ cells with an SH-1-immunophenotype in the peripheral blood, spleen, and bone marrow, as well as solid neoplasms in multiple organs. Moreover, the histologically infiltrated leukemic cells expressed CD45. In conclusion, the current study demonstrated the normal growth of SHI-1 cells in the NPG mice without immunosuppression, which caused systemic leukemia similar to that observed in acute leukemia patients. We developed an efficient and reproducible model to study leukemia pathogenesis and progression.
Open Access
Expression of CCL2 signaling pathway genes in patients with periodontitis and atherosclerosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhao, Yuxia; Wang, Lianqun; Dong, Rui; Cheng, Xuejun; Jia, Liqun; Qu, Dan; Zhang, Lin
Objective. Periodontitis and atherosclerosis are chronic inflammatory diseases characterized by leukocyte infiltration. We investigated the expression of CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 as well as the possible mechanism involved in the regulation of CCL2 in human periodontitis tissues and atherosclerotic aorta based on previous research on the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathway leading to CCL2 expression in collagen-induced arthritis (CIA) rat. Methods. Sixty-five volunteers were recruited and the condition of their gingiva and coronary arteries were assessed. The subjects were divided into four groups: healthy control, chronic periodontitis (CP), coronary artery diseases (CAD), and noncoronary artery diseases (non-CAD). Total RNA was isolated from gingiva in periodontitis patients and control populations and from the aorta in patients with and without CAD. PCR was used to examine CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 levels. The production of CCL2 in the gingiva and aorta was analyzed by immunostaining. Results. PCR revealed that CCL4, CCR5, and CCL2 mRNA levels were increased in CP patients' gingivae and aortas from coronary artery bypass grafting (CABG) patients. Marked c-Jun, c-Fos, and NF-κB gene productions were detected in CP patients’ gingivae but did not show statistical differences between the CAD and non-CAD groups. Stronger immunoreactivity against CCL2 was observed in periodontitis gingiva and aorta from CABG patients. Conclusions. Our findings suggest that the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathways may be involved in CCL2 expression in periodontitis. CCL4, CCR5, and CCL2 might act as possible nodes to link the presence of periodontitis and atherosclerosis.
Open Access
Chondroitin polymerizing factor (CHPF) promotes the progression of colorectal cancer through ASB2-mediated ubiquitylation of SMAD9
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhao, Jiang; Tang, Xiaolong; Zhu, Huijun
Chondroitin polymerizing factor (CHPF) has been reported to play a pivotal role in the progression of multiple cancers, however, the relationship between CHPF and colorectal cancer (CRC) progression has not been fully understood. The current study revealed that CHPF expression was upregulated in patients with CRC and correlated with an unfavorable prognosis. Also, CHPF knockdown effectively suppressed the viability and mobility of CRC cells and the growth of xenograft tumors. Additionally, SMAD9 was identified as a downstream target of CHPF. SMAD9 knockdown successfully abrogated the promotion of CHPF overexpression in CRC progression, indicating that CHPF regulated the development of CRC through SMAD9. Mechanistically, SMAD9 is ubiquitinated by ASB2, and the regulatory effect of CHPF on SMAD9 activity was exerted via its mediation of ASB2. Collectively, CHPF functioned as a promising prognostic biomarker and tumor-promoter of CRC by regulating the ASB2-mediated ubiquitination of SMAD9.
Open Access
“Vascular tuft sign” in neuroendocrine tumors of the pancreas
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Díaz Flores, L.; Gutiérrez, R.; García Suárez, M.P.; González Gómez, M.; Carrasco, J.L.; Díaz Flores Jr, L.; Madrid Cuevas, Juan Francisco
The often well-developed microvasculature in pancreatic neuroendocrine tumors (PanNETs) has been studied from different perspectives. However, some detailed structural findings have received less attention. Our objective is to study an overlooked event in PanNETs: “enclosed vascular tufts” (EVTs). For this purpose, 39 cases of PanNETs were examined with conventional (including serial sections) and immunochemistry procedures. In typical EVTs, the results show: 1) an insulated terminal vascular area, with a globular (glomeruloid) aspect, formed by a cluster of coiled microvessels, presenting CD31-, CD34-positive endothelial cells, αSMA-positive pericytes, and perivascular CD34-positive stromal cells/telocytes, separated by a pseudoglandular space from the surrounding trabeculae of tumor neuroendocrine cells; and 2) a pedicle joining the insulated terminal vascular area, with connective tissue tracts around the enclosing tumor trabeculae. EVTs predominate in the trabecular and nested gyriform pattern of PanNETs, with tumor trabeculae that follow a ribbon coil (winding ribbon pattern) around small vessels, which acquire a tufted image. In EVTs, secondary modifications may occur (fibrosis, hyalinization, myxoid changes, and calcification), coinciding or not with those of the connective tracts. In conclusion, the typical characteristics of unnoticed EVTs allow them to be considered as a morphological sign of PanNETs (a vascular tuft sign). Further in-depth studies are required, mainly to assess the molecular pathways that participate in vascular tuft formation and its pathophysiological implications
Open Access
Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Das, Shreya; Preethi, B; Kushwaha, Sapana; Shrivastava, Richa
Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting
Open Access
Urolithin A attenuates bupivacaine-induced neurotoxicity in SH-SY5Y cells by regulating the SIRT1-activated PI3K/AKT pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Liu, Bin; Wei, Yuan
Urolithin A (UroA) is well-recognized for its anti-oxidative, anti-inflammatory, and immuno-modulatory potentials and has been proven to have neuroprotective effects. Nevertheless, the potential of UroA on bupivacaine (BUP)-induced neurotoxicity has never been reported. Using SH-SY5Y cells to establish a cell model, it was revealed that BUP stimulated cell viability reduction, LDH release increase, and suppression of SIRT1-activated PI3K/AKT signaling in SH-SY5Y cells, whereas UroA treatment caused an effective abrogation of the effects of BUP. Besides, SIRT1 overexpression caused an enhancement in the activity of PI3K/AKT signaling in BUP and UroA co-treated cells, indicating that SIRT1 mediated the activity of PI3K/AKT signaling. Moreover, UroA inhibited BUP-induced apoptosis, oxidative stress, and inflammatory responses in SH-SY5Y cells. However, the effects of UroA on BUP-induced neurotoxicity were all abated by inhibiting SIRT1 or PI3K/AKT signaling through EX527 or LY294002. In conclusion, UroA protected SH-SY5Y cells against BUP-induced injuries through PI3K/AKT signaling in a SIRT1-dependent manner.

Browse

Browsing Histology and histopathology Vol.39,nº11 (2024) by Issue Date

Results Per Page

Sort Options