Cytojournal最新文献

Kikuchi's lymphadenitis (KL) is a benign, self-limited, reactive condition with unknown etiology, usually seen in young women of Asian descent. It is most commonly seen in the cervical lymph nodes; however, in rare cases, axillary lymph nodes are involved. Cytological diagnosis is possible with adequate lymph node sampling by fine needle aspiration in the proper clinical setting. Pathologists face some difficulties in making the diagnosis of KL due to overlapping findings among other conditions, such as tuberculosis, lupus lymphadenitis, non-specific reactive conditions, and even malignant lymphoma. Diagnosis by cytopathology has the advantage of using minimally invasive interventions, which avoid the unnecessary excision of the lymph node for this benign condition. Herein, we report a case of KL in a patient who presented with right axillary lymphadenopathy.

Objective: The immunosuppressive tumor microenvironment (TME) limits the treatment effectiveness of immunotherapy in gastric cancer (GC). This study investigated the role of membrane-spanning four domains subfamily A member 4A (MS4A4A) in the regulation of macrophage polarization and its effect on the immune response in GC, with the aim of enhancing the effectiveness of immunotherapy by addressing the immunosuppressive TME.

Material and methods: A GC ectopic tumor model was initiated in C57BL/6 mice with subcutaneous MKN-45 injection. Five groups were formed by randomly dividing the mice: model, MS4A4A recombinant protein, MS4A4A antibody, programmed cell death protein 1 (PD-1) antibody, and MS4A4A recombinant protein + PD-1 antibody groups. MKN-45 cells and bone marrow-derived macrophages (BMDMs) were cocultured with the MS4A4A protein or antibody. Macrophage polarization was analyzed through flow cytometry, gene expression through quantitative real-time polymerase chain reaction (qRT-PCR), cytokine levels through enzyme-linked immunosorbent assay, protein expression through Western blot, and tumor morphology through hematoxylin and eosin staining.

Results: In the GC mouse model, the MS4A4A recombinant protein markedly enhanced tumor growth (P < 0.001), and the MS4A4A antibody exhibited an inhibitory effect (P < 0.001). MS4A4A recombinant protein decreased the levels of inflammatory cytokine concentrations and increased those of anti-inflammatory mediator concentrations (P < 0.001). By contrast, the MS4A4A antibody treatment group displayed the opposite effect. Inhibition of MS4A4A enhanced the accumulation of macrophages, CD4⁺ T cells, and CD8⁺ T cells in the tumor (P < 0.001). Flow cytometry and qRT-PCR analyses showed that MS4A4A promoted M2 macrophage polarization, and MS4A4A antibody induced M1 polarization (P < 0.001). MS4A4A played a key role in inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells subunit p50 (p50) during M1 polarization. Furthermore, the PD-1 antibody reversed the pro-tumor effects of MS4A4A, which reestablished pro-inflammatory cytokine levels while lowering anti-inflammatory cytokines (P < 0.001).

Conclusion: This study shows that MS4A4A promotes tumor growth by inducing M2 macrophage polarization and suppressing immune responses, while MS4A4A antibody enhances anti-tumor immunity by inducing M1 polarization. PD-1 antibody reverses MS4A4A's pro-tumor effects, restoring anti-tumor immunity. MS4A4A inhibitors or their combination with PD-1 antibodies may offer a promising strategy for GC immunotherapy.

Objective: Acute cerebral infarction (ACI) has a high incidence and complex etiology, so searching for specific diagnosis and therapeutic target molecules is highly important. This paper aimed to explore the mechanism of karyopherin alpha 4 (KPNA4) in ACI.

Material and methods: Four groups were established: sham group, middle cerebral artery occlusion (MCAO) group, MCAO + small interfering negative control (si-NC group), and MCAO + si-KPNA4 group. The Zea-Longa scoring standard was adopted to assess the neurological impairment of ACI rats. The expression of KPNA4 was verified by real-time quantity polymerase chain reaction assay and Western blot. 2,3,5-Triphenyltetrazolium chloride and hematoxylin and eosin staining were used to examine the effects of KPNA4 knockdown on brain injury in ACI rats. The apoptosis of oxygen-glucose deprivation (OGD)-SH-SY5Y cells was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Western blot analysis was performed to analyze the expression levels of apoptosis-related proteins, inflammatory factors, and nuclear factor kappa B (NF-κB) pathway-related proteins.

Results: KPNA4 was overexpressed in the MCAO rat brain (P < 0.0001) and OGD-SH-SY5Y cells (P < 0.0001). Knocking down KPNA4 significantly reduced the degree of brain damage (P < 0.0001) and reduced the apoptosis of OGD-SH-SY5Y cells (P < 0.001). KPNA4 knockdown also significantly decreased the expression levels of inflammatory factors (interleukin [IL]-1β, tumor necrosis factor-α, and IL-18; P < 0.0001) and prohibited the phosphorylation of the inhibitor of NF-κB and p65 (P < 0.0001). However, NF-κB agonist lipopolysaccharide reversed the inhibition of KPNA4 knockdown.

Conclusion: In general, KPNA4 knockdown can mitigate ACI-induced damage by regulating the NF-kB pathway. This finding provides a new perspective on the treatment of ACI.

Objective: Coronary microvascular dysfunction following myocardial infarction (MI) serves as a critical factor affecting cardiac repair and functional recovery. Hyperhomocysteinemia (HHcy) has been closely associated with cardiovascular diseases, particularly in terms of its detrimental effects on microvasculature post-MI. Although transcription factor SP1 plays crucial roles in various physiological and pathological processes, its specific mechanism in the reversal of HHcy-induced microvascular dysfunction after MI remains unclear. The purpose of this study was to explore the possible mechanism of SP1 on HHcy-induced microvascular dysfunction.

Material and methods: This study utilized an HHcy mouse model and an in vitro model of human coronary artery endothelial cells (HCAECs) to systematically investigate the role of SP1 in post-MI microvascular dysfunction. Cardiac microvascular perfusion was assessed using fluorescein isothiocyanate (FITC)-labeled tomato lectin. Western blot analysis was employed to examine the expression levels of signal transducer and activator of transcription 3 (STAT3), conductance calcium-activated potassium channel protein 4 (KCNN4, also known as KCa3.1), and endothelial nitric oxide synthase (eNOS). The eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and STAT3 inhibitor Stattic were used to validate the signaling pathway.

Results: SP1 considerably improved microvascular dysfunction and angiogenic capacity in HHcy mice after MI. It enhanced cardiac microvascular function recovery by activating the STAT3/KCa3.1/eNOS signaling pathway. The eNOS inhibitor L-NAME reversed the protective effects of SP1, which indicates the crucial role of eNOS in SP1-mediated cardiovascular protection. Furthermore, SP1 alleviated homocysteine and hypoxia-induced cytotoxicity in HCAECs through this pathway, and the inhibition of the STAT3/KCa3.1/eNOS pathway blocked SP1's protective effects.

Conclusion: This study revealed for the first time the mechanism by which SP1 reverses HHcy-induced post-MI microvascular dysfunction through the activation of the STAT3/KCa3.1/eNOS pathway. The findings not only deepen our understanding of the pathological mechanisms of post-MI microvascular dysfunction but also provide an important theoretical basis for the development of new cardiovascular disease treatment strategies. SP1, as a potential therapeutic target, may play a crucial role in future cardiovascular disease treatments.

Objective: Clear-cell renal cell carcinoma (ccRCC) is the most prevalent type of renal cancer. Solute carrier family 6 member 3 (SLC6A3) is associated with ccRCC. This research aimed to investigate the function of SLC6A3 in promoting the metabolism and development of ccRCC tumor cells.

Material and methods: SLC6A3 expression levels in ccRCC cell lines were assessed through quantitative real-time polymerase chain reaction and Western blot (WB). A stable overexpression of SLC6A3 was achieved in the 786-O cell line, and stable knockdown was established in the OS-RC-2 cell line through lentiviral transfection. Cell biological behavior was evaluated through flow cytometry, terminal deoxynucleotidyl transferase media dUTP nick end labeling staining, Cell counting kit-8 assays, and Transwell assays. Extracellular acidification rate measurements, WB, and biochemical assays were performed to detect cellular glycolysis and ferroptosis following alterations in SLC6A3 expression. The effects of SLC6A3 overexpression or knockdown on ccRCC tumor were further verified in xenograft models using nude mice.

Results: SLC6A3 was elevated in various ccRCC cell lines. The 786-O cells exhibited a relatively low baseline SLC6A3 expression (P < 0.01), which prompted subsequent overexpression experiments, whereas OSRC-2 cells showed the highest baseline expression (P < 0.001), which led to subsequent knockdown studies. The overexpression of SLC6A3 in 786-O cells increased the glycolytic activity, decreased ferroptosis levels, and promoted viability and invasion of ccRCC cells. Conversely, knockdown of SLC6A3 in OS-RC-2 cells reduced glycolytic activity, increased ferroptosis levels, and inhibited viability and invasion of ccRCC cells. All results were statistically significant. These findings were corroborated by in vivo experiments.

Conclusion: SLC6A3 is markedly overexpressed in ccRCC. It influences the promotion of tumor growth by enhancing glycolysis and suppressing ferroptosis. These insights highlight the potential of SLC6A3 for innovative therapeutic strategies in ccRCC management.

Metaplastic breast carcinoma comprises a heterogeneous group of morphologic variants characterized by markedly aggressive pathological behavior and diverse histological subtypes. Accurate diagnosis of metaplastic breast carcinoma is essential for implementing effective and individualized treatment approaches; however, its differentiation from similar tumors may occasionally be challenging. We report two cases of breast tumors diagnosed using comprehensive tumor genome analysis.

Lung cancer is the leading cause of cancer-related deaths worldwide, with genetic- and protein-based diagnostics playing a crucial role in disease detection and improving patient outcomes. Glycosylation, a major post-translational modification, has recently emerged as a factor influencing cancer progression, immune evasion, and therapeutic resistance. Aberrant glycosylation patterns, particularly among receptor tyrosine kinases (RTKs), have been shown to modulate oncogenic signaling pathways and influence tumor growth. This review provides a comprehensive overview of how glycosylation alterations affect the stability, function, and therapeutic targeting of key RTKs relevant in lung adenocarcinoma: Epidermal growth factor receptor, human epidermal growth factor receptor 2, and cellular mesenchymal-epithelial transition factor, rearranged during transfection, anaplastic lymphoma kinase, and ROS proto-oncogene 1 receptor tyrosine kinase. Despite substantial advances in targeted therapies, initial and acquired resistance remain a major challenge in the treatment of lung cancer. There is growing evidence that strategies targeting glycosylation can be combined with established treatment protocols to help overcome resistance. Finally, we propose future directions for the advancement of glycosylation-based approaches to improve precision medicine.

Objective: This study aims to explore the role of microfibrillar-associated protein-2 (MFAP2) in oral squamous cell carcinoma (OSCC).

Material and methods: Analysis of MFAP2 expression in diverse cancers and its relationship with head-and-neck squamous cell carcinoma (HNSC) prognosis. MFAP2 abundance was identified in OSCC cells and in human oral epithelial cells using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays. Knockdown and overexpression techniques were utilized to examine the mechanism by which MFAP2 and nuclear factor erythroid 2-related factor 2 (NRF2) affect OSCC malignancy. Cell viability, proliferation, and apoptosis were assessed using cell counting kit-8, colony formation, flow cytometry, wound healing, and Transwell tests. Messenger ribonucleic acid expression was detected using qRT-PCR, whereas protein level was analyzed using Western blot.

Results: MFAP2 and Kelch-like E3 ubiquitin ligase (ECH)-associated protein 1 (KEAP1) had high expression levels in numerous tumors, including OSCC, and the high expression level of MFAP2 was associated with unfavorable HNSC outcomes. MFAP2 was abundantly expressed in five OSCC cell lines, with the peak expression observed in squamous cell carcinoma (SCC)-15 and SCC-9 cells, making them suitable for subsequent studies. MFAP2 knockdown hindered the proliferative and mobile capacity of OSCC cells, yet it supported cell apoptosis. MFAP2 silencing led to a notable drop in KEAP1 and NRF2 expression levels in OSCC cells. NRF2 overexpression could counteract the effects of MFAP2 knockout, which included diminished proliferation and movement and heightened apoptosis in OSCC cells.

Conclusion: The results of this study indicated that MFAP2 facilitated the malignant progression of OSCC and provided insights into the downstream regulatory mechanism of the KEAP1/NRF2 axis, highlighting the potential application of MFAP2 in OSCC management.