Cytojournal最新文献

Objective: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. Research indicates that N6-methyladenosine (m6A) modification plays a crucial role in cellular autophagy during ALS development. This study investigates the role of autophagy in ALS, with a focus on the effect of messenger ribonucleic acid m6A methylation modification on disease progression.

Material and methods: We compared m6A levels and regulatory molecule expressions in transgenic superoxide dismutase (SOD1)-G93A and non-transgenic mice, categorized into end-stage and control groups, using quantitative polymerase chain reaction and Western blotting. The NSC-34 cell line, which was modified to model ALS, enabled the investigation of apoptosis, autophagy, and autophagy disruption through terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assays, Western blotting, and fluorescent staining.

Results: Our findings indicate significantly elevated m6A methylation levels in ALS mice (0.262 ± 0.005) compared with the controls (0.231 ± 0.003) and in the ALS model cells (0.242±0.005) relative to those belonging to the wild-type control group (0.183 ± 0.007). Furthermore, the proteins involved in m6A RNA modification differed between groups, which suggest impaired autophagy flux in the ALS models.

Conclusion: These results suggest that m6A methylation may accelerate ALS progression through the disruption of autophagic processes. Our study underscores the role of m6A methylation in the pathology of ALS and proposes the targeting of m6A methylation as a potential therapeutic strategy for disease treatment. Although this study primarily used transgenic SOD1-G93A mice and NSC-34 cell models to investigate ALS pathology, potential differences in disease mechanisms between animal models and humans must be considered. Although a correlation was detected between m6A methylation levels and autophagy disruption in ALS, the study primarily established an association rather than provided detailed mechanistic insights.

Objective: Recent evidence suggests the involvement of senescence and inflammation in abdominal aortic aneurysm (AAA). Considering the role of sirtuin-1 (SIRT1) in delaying senescence, we aimed to preliminarily investigate the potential mechanism underlying the effects of SIRT1 in senescence and inflammation during AAA.

Material and methods: A cell AAA model was established using angiotensin II (Ang II) as the inducer, which was applied to treat human aortic vascular smooth muscle cells (HASMCs). The senescence and cell cycle of treated HASMCs were evaluated based on senescence-associated (SA)-b-galactosidase (b-gal) assay and flow cytometry, respectively. The levels of inflammatory cytokines and proteins related to senescence-associated secretory phenotype (SASP), along with nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinases (MAPK) pathways, as well as SIRT1, were gauged. The correlation between SIRT1 and NF-kB and MAPK pathway-related proteins was further estimated.

Results: In Ang II-treated HASMCs, reduced SIRT1 and B-cell lymphoma-2 levels yet increased levels of SASP-related proteins P16 and P21, inflammatory cytokines, as well as Bax and caspases were all visible. In the meantime, Ang II exposure enhanced the number of b-gal-positive HASMCs and promoted cell cycle arrest. SIRT1 was also repressed following Ang II treatment and negatively correlated with NF-kB and MAPK pathway-related proteins (P < 0.05). Furthermore, the overexpression of SIRT1 diminished the levels of SASP-related proteins and reduced the phosphorylation of extracellular regulated kinase 1/2 and P65 in Ang II-treated HASMCs (P < 0.05).

Conclusion: Taken together, our results indicate that SIRT1 overexpression attenuates the inflammatory and senescent responses of HASMCs in the Ang II-induced AAA cell model. This finding suggests that SIRT1 can be a highly promising target for clinical treatment of AAA.

Objective: Benign histiocytic proliferation in effusion specimens can be found in a variety of diseases such as rheumatoid arthritis, systemic lupus erythematosus, microorganism infections, trauma, reactive eosinophilic pleuritis, and others. In addition, nodular histiocytic/mesothelial hyperplasia is another well-recognized rare cause. The previous studies have shown that proliferative histiocytes have raisinoid nuclei and abundant eosinophilic granular cytoplasm and can be confused with malignant lesions, especially metastatic carcinomas. In this study, we evaluated the cytomorphology of benign histiocytes, discussed the diagnosis and differential diagnosis, and the clinical significance of histiocytic signet ring cells in effusion cytology.

Material and methods: Seven hundred and fifty-five benign effusion cases (433 pleural effusions and 322 abdominal fluids) were found over 1 year. Among benign cases, 35 cases (28 pleural effusions and seven abdominal fluids) were included with findings of dominantly histiocytic signet ring cell morphology as well as immunohistochemical (IHC) stains. The clinical findings were also correlated.

Results: In contrast to the well-documented cytomorphology of raisinoid nuclei and eosinophilic cytoplasm of proliferative histiocytes in previous studies, we find that these cells predominately presented as signet ring cell morphology with clear cytoplasm. The most characteristic findings of benign histiocytes in pleural effusions are: (1) cells are arranged in sheets and/or scattered individual cells, but no two- or three-dimensional cell clusters; (2) cells are intermediate in size and with normal N/C ratio; (3) cells have eccentric located nuclei and abundant clear cytoplasm, giving signet ring cell appearance; (4) nuclei have fine granular chromatin pattern, no hyperchromia or coarse chromatin pattern, no nuclear atypia; and (5) immunohistochemical (IHC) stains demonstrate a strongly positivity for macrophage-histiocyte lineage marker CD68, but negativity for epithelial markers and mesothelial markers. Clinically, these patients do not demonstrate nodularity or lesions in the mesothelial lining of serous cavities.

Conclusion: Our study provides a detailed characterization of benign histiocytic signet ring cells in effusion cytology. The differential diagnosis of histiocytic signet ring cells is broad. The most important differential diagnoses are metastatic adenocarcinoma and epithelioid signet ring cell mesothelioma. The accurate diagnosis is critical for the appropriate clinical management of the patient. Cytopathologists should be aware of the diagnostic pitfalls of benign histiocytic signet ring cells in effusion samples in daily practice.

In the ever-evolving landscape of oncology, the battle against prostate cancer (PCa) stands at a transformative juncture, propelled by the integration of molecular diagnostics into traditional cytopathological frameworks. This synthesis not only heralds a new epoch of precision medicine but also significantly enhances our understanding of the disease's genetic intricacies. Our comprehensive review navigates through the latest advancements in molecular biomarkers and their detection technologies, illuminating the potential these innovations hold for the clinical realm. With PCa persisting as one of the most common malignancies among men globally, the quest for early and precise diagnostic methods has never been more critical. The spotlight in this endeavor shines on the molecular diagnostics that reveal the genetic underpinnings of PCa, offering insights into its onset, progression, and resistance to conventional therapies. Among the genetic aberrations, the TMPRSS2-ERG fusion and mutations in genes such as phosphatase and tensin homolog (PTEN) and myelocytomatosis viral oncogene homolog (MYC) are identified as significant players in the disease's pathology, providing not only diagnostic markers but also potential therapeutic targets. This review underscores a multimodal diagnostic approach, merging molecular diagnostics with cytopathology, as a cornerstone in managing PCa effectively. This strategy promises a future where treatment is not only tailored to the individual's genetic makeup but also anticipates the disease's trajectory, offering hope for improved prognosis and quality of life for patients.

Objective: Studies have shown that chemokines can stimulate the migration and activation of microglia to cause chronic post-surgical pain (CPSP). However, the involvement of C-X-C motif chemokine receptor 2 (CXCR2) as a new chemotactic factor in regulating CPSP and its underlying mechanism remains unclear. This study is to investigate the role of CXCR2 in the development of CPSP and reveal the underlying mechanism.

Material and methods: A rat model of skin/muscle incision and retraction was established, and treated with or without SB225002 (a selective inhibitor of CXCR2). In addition, the primary microglia cells induced by lipopolysaccharide were applied as an in vitro model for CPSP and treated individually with si-negative control (NC), si-CXCR2, si-CXCR2+Interleukin (IL)-6 (an agonist of the janus kinase (JAK)/signal transducers and activators of transcription (STAT)3 signaling pathway), si-CXCR2+IL-6+si-NC, or si-CXCR2+IL-6+si-exchange protein 1 directly activated by cAMP (EPAC1).

Results: Results from the database analysis showed that CXCR2 and JAK/STAT3 signaling pathway-related genes, including JAK1, STAT3, and EPAC1, were mainly involved in the development of CPSP. Inhibition of CXCR2 expression not only inhibited the reduction of foot pain threshold in CPSP models but also led to a decreased expression of CXCR2 and the phosphorylation levels of JAK and STAT3 in both animal and cell models. Furthermore, inhibition of EPAC1 expression can hinder the regulatory function of CXCR2.

Conclusion: This study indicated that the high expression of CXCR2 activates the JAK1/STAT3 signaling pathway, enhances EPAC1 activation in microglial cells, and exacerbates CPSP.

Objective: The accurate diagnosis of thyroid nodules is crucial for effective management and the detection of malignancy. Fine-needle aspiration biopsy (FNAB) and fine-needle non-aspiration biopsy (FNNAB) are widely used techniques for evaluating thyroid nodules. In this study, we aimed to investigate the impact of anthropometric parameters and sonographic characteristics on the choice between FNAB and FNNAB in terms of diagnostic yield.

Material and methods: This retrospective and cross-sectional analysis involved 188 cases with a total of 225 thyroid nodules. Each nodule initially underwent either FNAB or FNNAB and if the initial biopsy did not yield a diagnostic result, the nodule was re-biopsied using the alternate technique. Ultrasound was used to evaluate the nodules, with a focus on echogenicity, calcifications, size, vascularity, and the presence of a halo sign. Both FNAB and FNNAB were performed using a 25-gauge needle, with the only difference being the application of suction.

Results: FNAB demonstrated a higher diagnostic rate for nodules with a taller-than-wide shape (anteroposteriorto-transverse ratio ≥1), nodules sized 10-40 mm, nodules with volumes <0.5 cc, and hypoechoic nodules (P < 0.001 for all). FNAB also outperformed FNNAB in the assessment of the right-sided, inferior, and posterior nodules (P < 0.001), nodules with and without calcification (P = 0.041 and P = 0.020, respectively), and nodules with type 1 and type 2 vascularity patterns (P = 0.006 and P = 0.017, respectively). FNAB was effective in obese individuals (Body mass index ≥40 kg/m²), males with a waist circumference of <94 cm, females with a waist circumference of ≥80 cm, and females with a neck circumference of ≥34 cm (P = 0.011, P = 0.044, P = 0.029, and P = 0.008, respectively).

Conclusion: Anthropometric parameters and sonographic characteristics influenced the diagnostic yield of FNAB and FNNAB, with FNAB generally demonstrating superior results. Given the importance of obtaining an accurate diagnostic result from fine-needle biopsy, clinicians should consider both the sonographic features of the nodule and the anthropometric measurements of the patient when selecting a biopsy technique.