Analytical Cellular Pathology最新文献

In recent years, researchers have focused on the drug capacity of natural products and their components with low side effects in the treatment of leukemia. This study aims to elucidate the antileukemic mechanism of action of olive oil extract of propolis (OEP) together with methylprednisolone (MP) in HL-60 cells, an acute myeloid leukemia cell line. The WST-8 kit was used to test the cytotoxic and proliferative effects of OEP on HL-60 cells. Flow cytometry was additionally applied for determining apoptotic status, cell cycle, and differentiation levels (CD11b, CD14, and CD68). The IC₅₀ concentration of OEP in HL-60 cells was determined to be 0.5 μ L/mL after a 24 h period. OEP effectively arrested the cell cycle at the G₂/M phase after 24 h, and its addition of MP strengthened this effect. After 48 h, OEP significantly inhibited the cell cycle at the G₂/M phase. The combination of OEP with MP led to significantly greater numbers of cells arrested in the G₀/G₁ phase. OEP alone has shown significant efficacy in encouraging apoptosis; however, its combination with MP provided considerably more beneficial effects. The OEP performed efficiently at CD11 levels for the first 24 h. Due to its impact on apoptosis, cell cycle arrest, and differentiation, OEP may be a natural product that merits additional preclinical investigation in leukemia models. The combined effects of OEP and MP on stopping the cell cycle provide a possible way to treat leukemia. Additional research is required to investigate the processes underlying the improved efficacy of the combo-therapy.

Objective: The present investigation was aimed to examine ubiquitin-conjugating enzyme E2S (UBE2S), hypoxia-inducible factor (HIF)-1α, and factor forkhead box M1 (FOXM1) levels in esophageal squamous cell carcinoma (ESCC) and esophageal low-grade intraepithelial neoplasia (LIN), high-grade intraepithelial neoplasia (HIN). Additionally, the investigation explored the correlation between these levels and clinicopathological features in addition to prognosis.

Methods: To investigate the expression patterns of UBE2S, HIF-1α, and FOXM1, immunohistochemical staining was performed on tissue samples, including LIN, HIN, ESCC, and healthy controls. Subsequently, the chi-square test was applied to analyze the correlations between the expression levels of the three proteins and the clinicopathological features of ESCC. The impact of UBE2S, HIF-1α, and FOXM1 on ESCC prognosis was evaluated using survival analysis. Spearman correlation analysis was employed to analyze the correlation of three proteins in ESCC, HIN, and LIN, respectively.

Results: UBE2S overexpression was related to ethnicity (p < 0.001) and the place of the tumor (p = 0.021). Overexpression of HIF-1α (p = 0.017) and FOXM1 (p = 0.015) was connected to metastasis of the lymph node. Individuals with elevated levels of UBE2S, HIF-1α, and FOXM1 had reduced overall survival (OS) and progression-free survival (PFS).

Conclusion: The expression levels of UBE2S, HIF-1α, and FOXM1 are closely associated with the incidence and progression of ESCC. UBE2S, HIF-1α, and FOXM1 have potential as prognostic indicators for ESCC.

Background: Protein arginine methyltransferase 9 (PRMT9) is dysregulated in various malignancies, particularly in lung adenocarcinoma (LUAD). This study aims to systematically investigate the expression patterns, biological functions, and underlying molecular mechanisms of PRMT9 in LUAD pathogenesis.

Methods: PRMT9 expression was evaluated in paired clinical LUAD specimens and adjacent normal tissues, as well as in normal alveolar epithelial cells versus established lung cancer cell lines. Genetic silencing of PRMT9 was performed in A549 and H1568 cell models to assess its functional impact. Cellular migratory and invasive capacities were quantified using wound healing and Transwell invasion assays. The mechanism of PRMT9 overexpression was explored by examining m6A-mediated mRNA modification. The role of IGF2BP1 was determined through loss-of-function and gain-of-function experiments, supplemented with studies under PRMT9-deficient conditions. Downstream signaling was investigated using specific inhibitors targeting the RAS and MAPK pathways, with in vivo validation in xenograft models.

Results: PRMT9 was significantly upregulated at both transcriptional and translational levels in LUAD tissues and cancer cell lines compared to normal controls. Genetic depletion of PRMT9 substantially impaired cell migration and invasion, and suppressed activation of the RAS/MEK/ERK signaling pathway. The aberrant expression of PRMT9 was mechanistically linked to IGF2BP1-regulated m6A modification. IGF2BP1 was similarly overexpressed in LUAD specimens and cell models. Knockdown of IGF2BP1 reduced PRMT9 m6A modification, compromised cell viability, migration, and invasion, and attenuated RAS/MEK/ERK signaling. Conversely, IGF2BP1 overexpression enhanced malignant behaviors, effects that were reversed by concurrent PRMT9 knockdown. Mechanistically, PRMT9 overexpression activated the RAS/MAPK signaling axis, and pharmacological inhibition of this pathway mitigated PRMT9-mediated metastatic progression. In vivo studies confirmed that PRMT9 suppression inhibited tumor growth, which was associated with decreased expression of RAS, pMek1/2, pErk1/2, and Ki67, alongside enhanced caspase-3 expression.

Conclusion: PRMT9 is overexpressed in LUAD and promotes malignant progression by activating the RAS/MAPK signaling cascade. This aberrant PRMT9 expression is governed by IGF2BP1-mediated m6A modification. These findings suggest that therapeutic targeting of PRMT9 or the RAS/MAPK signaling axis may represent a promising strategy for LUAD treatment.

Background: Ankylosing spondylitis (AS) is an autoimmune disease characterized by low back stiffness and pain, with no cure and a dearth of therapeutic targets.

Methods: Identifying novel AS targets from a list of 5884 druggable genes using weighted gene coexpression network analysis (WGCNA), machine learning, and Mendelian randomization analysis. Investigating the biological functions of the targets through comprehensive bio-functional analyses; exploring immune-related functions of the targets based on single-cell analyses; developing a reliable AS risk prediction model based on the identified targets and clinical data; conducting target drug prediction and molecular docking based on the Enrichr database and the LeDock software.

Results: A novel AS target, diazepam binding inhibitor (DBI), was identified from among 5884 druggable genes. Bio-functional enrichment analysis indicated that this gene plays a key role in AS by modulating lipid metabolism disorders. Furthermore, single-cell analysis revealed that the gene likely influences the onset or progression of AS by impairing the cytotoxic function of CD56^dim natural killer (NK) cells. Finally, a reliable AS risk prediction model was developed using DBI and clinical data, and several potential therapeutic compounds were identified.

Conclusion: In this study, a novel therapeutic target for AS was identified using multiple algorithms, and it was found to be involved in lipid metabolism and cytotoxic function of CD56^dim NK cells. Additionally, a reliable prediction model was developed, and potential therapeutic compounds were identified. In conclusion, this study presents a novel approach for AS treatment.

[This retracts the article DOI: 10.1155/2021/6615979.].

Inflammatory myofibroblastic tumors (IMTs) are rare neoplasms found in diverse anatomical sites, including the lungs, intestines, and bladder. Surgical resection is the primary treatment, with chemotherapy offering survival rates of 21.2 and 42.5 months in unresectable cases. Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have emerged as standard treatments. However, IMT presents diagnostic challenges owing to its morphological similarities with other conditions. While positive ALK expression aids diagnosis in approximately 50% of the cases, negative ALK expression complicates diagnosis. This retrospective study reviewed 48 patients with IMT diagnosed at a Taiwanese medical center and analyzed their clinical characteristics, pathology reports, immunohistochemical (IHC) staining profiles, and outcomes. Chi-square and independent t-tests were used for the statistical analysis. The results showed an equal sex distribution, with the gastrointestinal tract being the most prevalent site, followed by the urinary system and lungs. Positive ALK expression was observed in 12 patients. While no statistically significant differences were found between ALK expression and age, sex, or site of occurrence, a younger mean age was noted in the ALK-positive group, which is consistent with the existing literature. Moreover, ALK negativity tended to occur in the nonvisceral organs (head and neck, extremities, and genitals). Regarding IHC staining, smooth muscle actin (SMA) was positive in 74.5% of cases, whereas S-100 protein, CD34, CD117, myogenin, and DOG1 were consistently negative. For desmin and cytokeratin, the results differed among cases and may not be used as determinant factors to diagnose such diseases. We hope that this investigation will be a cornerstone for further studies on the diagnosis of IMT in the absence of ALK rearrangements.

[This retracts the article DOI: 10.1155/2021/6668947.].

Backgrounds: Asthma causes over 1000 deaths daily worldwide and is becoming one of the most prevalent and severe respiratory diseases. This study aimed to investigate the therapeutic effects of Platycodon grandiflorum extract (PGE) on asthma both in vivo and in vitro.

Methods: Thirty Sprague-Dawley (SD) rats were divided into named control (NC), asthma, and PGE high-, medium-, and low-dose groups. The PGE groups were intragastrically administered the drug for 14 days. After treatment, pathological changes were observed using histological staining. Flow cytometry was used to observe changes in inflammatory cells. The expression of the toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway proteins was detected using western blotting. Additionally, lipopolysaccharide (LPS)-stimulated rat tracheal epithelial (RTE) cells were used for validation in vitro.

Results: Histological staining revealed smooth muscle hyperplasia and inflammatory cell infiltration in asthmatic mice. The pathological condition of the lung tissue of rats in all treatment groups improved, with the high-dose group showing the most significant improvement. PGE treatment reduced the number of inflammatory cells recruited in the lung of asthmatic rats, and reduced tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels. Western blotting showed that TLR4 and p-P65 levels decreased significantly after PGE administration (p  < 0.05). Additionally, PGE treatment decreased apoptosis in LPS-stimulated RTE cells and decreased TNF-α, IL-1β, and IL-6 levels.

Conclusions: PGE inhibited inflammatory responses in asthmatic rats, which was validated at the cellular level. This therapeutic mechanism may be achieved through the regulation of the TLR4/NF-κB pathway.

This paper focuses on celiac disease (CD), an autoimmune disorder characterized by small intestinal enteropathy and gastrointestinal symptoms. The prevalence of CD is rising, and there is a need for prompt and accurate diagnosis. The paper discusses the challenges in classifying CD and the consequences of delayed diagnosis, including increased morbidity and mortality rates. It also highlights the Marsh classification, which categorizes CD based on histological characteristics. However, this classification has limitations, which can lead to misdiagnosis. The emergence of multiomics data and artificial intelligence (AI) is presented as a potential solution to improve CD diagnosis and management. Multiomics data integration enables a more precise diagnosis, while AI and machine learning (ML) techniques facilitate the identification of clinically relevant patterns and the development of diagnostic models. According to the findings, the integration of AI and multiomics data holds transformative potential for the diagnosis and management of CD, facilitating early diagnosis and personalized treatment strategies. AI-assisted methods, including video capsule endoscopy (VCE) analysis, have shown sensitivities exceeding 90%, enhancing diagnostic accuracy while reducing invasiveness. As novel biomarkers are identified, individualized management approaches can evolve, leading to improved patient outcomes, though further efforts are needed to standardize these technologies in clinical practice.

Lycium barbarum polysaccharides (LBP) displays some antidiabetic effects, but the mechanism is partial disclosure of its preventive activities related to insulin signaling and hepatic glucose metabolism. This study investigates the beneficial effect of LBP on insulin resistance and hepatic glucose production (HGP) in 30 mM glucose induced insulin resistant HepG2 cells (IR-HepG2) and high fat diet/streptozotocin induced diabetic mice. Additionally, the subacute toxicity of 14-day-administration of LBP was assessed in C57BL/6 mice. The results showed that LBP effectively reverted the inhibition of protein kinase B (AKT) and glycogen synthase 3 (GSK3) phosphorylation and countered the elevation of reactive oxygen species (ROS) in IR-HepG2 triggered by 30 mM glucose. Furthermore, LBP prevented the decline of glucose transporter isoform 2 (GLUT2) level in the diabetic mice liver and restored reduced glucose consumption and uptake in IR-HepG2. LBP also prevented the decrease in glycogen synthase (GYS2) mRNA expression and the reduction of liver glycogen content in diabetes mellitus (DM) mice. Moreover, LBP downregulated the expressions of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) to inhibit gluconeogenesis, while upregulated the expressions of glucokinase (GK), phosphofructokinase 1 (PFK1) and pyruvate kinase (PK) to activate glycolysis via the AMP-activated protein kinase (AMPK) signaling pathway in DM mice. No observed toxicity was found in both HepG2 cells and C57BL/6 mice under the tested conditions and doses. These findings suggest that LBP improves insulin sensitivity in high glucose induced IR-HepG2 and reduces HGP by regulating glucose uptake, glycogen synthesis and gluconeogenic/glycolytic flux. It may serve as a potential therapeutic approach for diabetes treatment.