Analytical Cellular Pathology最新文献

[This retracts the article DOI: 10.1155/2021/6622713.].

The purpose of this study was to investigate the impact of sevoflurane (SEV) on cardiomyocyte (CM) pyroptosis following myocardial ischemia (MI). Reverse validation was performed by pharmacologically activating NLRP3 with monosodium urate (MSU) to confirm that SEV's cardioprotective effects were specifically mediated through the NLRP3 inflammasome pathway. Sprague Dawley rats were randomly assigned to sham (sham), model (conventional anesthesia + MI-reperfusion [MIR] injury modeling), SEV (SEV inhalation anesthesia + MIR injury modeling), and SEV + NLRP3 (SEV inhalation anesthesia + MIR injury modeling + NLRP3) groups. The myocardial area at risk (MAAR) and the myocardial infarct size (MIS) were evaluated in each experimental group, and cardiac tissue was examined using hematoxylin-eosin (H&E), Masson trichrome, and TUNEL staining. The concentrations of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), oxidative stress (OS), and pyroptosis-associated proteins and various inflammatory markers in the serum and cardiac tissue were quantified. Results showed that compared to the sham group, both model and SEV groups exhibited a significant increase in MAAR and MIS, accompanied by severe histopathological damage and noticeable OS (p  < 0.05). Elevated levels of inflammatory factors, enhanced CM apoptosis, and increased expression of pyroptosis-associated proteins were also observed in these groups. Notably, the SEV intervention in the SEV group demonstrated evident mitigation of heart injury, reduced MAAR and MIS, diminished CM apoptosis and inflammatory factors, and suppressed pyroptosis-associated proteins. Additionally, we observed that NLRP3 activation significantly diminished the protective effects of SEV on MIR rats. This study uncovers a novel mechanism through which SEV suppresses CM pyroptosis by inhibiting NLRP3, as confirmed by pharmacological activation of NLRP3. This was evidenced by worsened histopathological damage, increased CM apoptosis, and higher levels of inflammatory factors, cardiac injury markers, and pyroptosis-associated proteins. Overall, SEV inhibits CM pyroptosis and mitigates OS and inflammation through the NLRP3 inflammasome.

[This retracts the article DOI: 10.1155/2020/6403012.].

Introduction: Expression of P16ink4A and FOXP3 is correlated with the grades of cervical lesions. In this study, we determined the diagnostic accuracy of serum P16ink4A and FOXP3 concentrations for detection of cervical intraepithelial neoplasia (CIN) and cervical cancer (CC) in a rural setting in Southwestern Uganda. Material and Methods: CIN and CC cases (93 each before treatment), and 93 controls were identified. Clinical and demographic data were documented before quantifying serum P16ink4A and FOXP3 concentrations using quantitative ELISA kits. Cases were confirmed by cytology and/or histology. We employed descriptive statistics, cross-tabulation, and receiver operating curves (ROC) using statistical software for data science (STATA) 17. p-values <0.05 were considered statistically significant. Results: Serum FOXP3 concentration of 0.0545 ng/mL < showed moderate sensitivity (32.22% and 57.78%) for detection of CIN and CC from healthy controls, respectively. It also showed a moderately high specificity of 68.89% for detection of both CIN and CC from healthy controls (AUC-0.6014 and 0.7679, respectively). Serum P16ink4A concentration of 0.946 ng/mL < showed moderate sensitivities (50.00% and 60.00%) and specificities (56.67% and 55.56%) for the detection of CIN and CC from healthy controls, respectively (AUC-0.6085 and 0.7592, respectively). A combination of elevated serum FOXP3 and P16ink4A showed very low sensitivities of 18.89% in detecting CIN from healthy controls and 33.33% for detecting CC from healthy controls. This combination showed high specificity of 83.33% in detecting both CIN and CC from healthy controls (AUC-0.5992 and 0.7642, respectively). Conclusion: Although serum P16ink4A and FOXP3 concentrations showed moderate accuracy, their combination was more specific than sensitive. This combination has a high potential to be applied for diagnosis rather than screening for cervical lesions, at least in the Ugandan population. Combinations of P16ink4A and FOXP3 with other biomarkers could improve diagnostic accuracies. Additionally, studies could be conducted to assess the performance of these biomarkers in the detection of cervical lesions in specific populations, say Human Immunodeficiency Virus (HIV)-positive and HIV-negative populations.

Objective: This study aims to assess the potential of vascular endothelial injury markers, namely, P-selectin (PS), vascular endothelial cadherin (VE-Cad), and vascular cell adhesion molecule-1 (VCAM-1), as diagnostic and prognostic biomarkers for ABO hemolytic disease of the fetus and newborn (HDFN). Methods: A total of 218 pregnant women with ABO blood group incompatibility were recruited from the Third People's Hospital of Bengbu Affiliated to Bengbu Medical University. The serum levels of PS, VCAM-1, and VE-Cad were measured, and the participants were followed up until postpartum. The women were divided into an HDFN group and a control group based on the occurrence of ABO-HDFN. The correlations between the three vascular endothelial injury markers, pregnant anti-A/B antibody titers, and the occurrence and severity of HDFN were analyzed. Results: Compared to the control group, the levels of PS, VCAM-1, and VE-Cad were significantly elevated in the HDFN group. Additionally, these markers increased with higher IgG anti-A/B titers. For diagnosing HDFN, the area under the curve (AUC) for PS, VCAM-1, and VE-Cad were 0.826, 0.765, and 0.799, respectively. Moreover, the combined AUC of the three markers with IgG anti-A/B titers was 0.9. The levels of the three biomarkers were significantly negatively correlated with neonatal hemoglobin (Hb) and significantly positively correlated with reticulocyte percentage (Ret%), indirect bilirubin (IBIL), and lactate dehydrogenase (LDH). Univariate logistic regression indicated that increased levels of PS, VCAM-1, and VE-Cad were associated with a higher probability of ABO-HDFN. Multivariate logistic regression revealed that PS is an independent positive factor for HDFN. Conclusion: PS, VCAM-1, and VE-Cad provide experimental evidence for prenatal screening, diagnosis, early prevention and treatment of ABO-HDFN.

Ovarian cancer is one of the leading malignant women tumors that causes higher mortality, and immunotherapy has shown high potential in the treatment of advanced ovarian cancer patients by activating and mobilizing the human immune system, which can improve patient prognosis and survival. Natural compounds are a big resource for screening and finding effective lead compounds to treat diseases. Gallic acid (GA) is a natural organic acid with broad-spectrum antibacterial, antiviral, and antitumor effects. In the current study, we aim to explore the effect of GA on ovarian cancer and its underlying mechanisms. The CCK-8 assay was employed to study its anti-proliferation effect and wound healing, and transwell assay was utilized to test the GA effect on cell migration and invasion. The xenograft tumor model was used to evaluate the GA anticancer effect in vivo. The results demonstrated that GA significantly suppresses the proliferation of ovarian cancer cells both in vitro and in vivo, reduces their migration and invasion capability, and enhances macrophage cytotoxicity in the murine ID8 xenograft tumor microenvironment (TME). The mechanism study demonstrated that its anticancer effect and enhancing immunity is stem from inhibiting the PI3k-AKT pathway. In conclusion, GA plays an anticancer effect via blockage of the PI3K-AKT pathway.

Cisplatin-based chemotherapy resistance is a common issue for cancer clinical efficacy. Metformin is being studied for its possible anticancer effect. The present study aimed to investigate whether metformin affects the chemosensitivity of gastric cancer to cisplatin and reveal the molecular mechanism. In this study, the effects of combination therapy with metformin and cisplatin on cell viability, cell apoptosis, malondialdehyde, superoxide dismutase, reactive oxygen species level, glucose uptake, lactate production, protein level, and xenograft tumor formation were analyzed in gastric cancer cells. Immunohistochemical staining was performed to detect Ki67 expression in matched tumor samples. The results showed that NCI-N87 and SNU-16 cells were most resistant and sensitive to cisplatin, respectively. Metformin treatment increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Furthermore, overexpression of nuclear factor erythroid 2-related factor 2 (Nrf2) reversed the effects of metformin in the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Metformin activated p53 and AMPK pathways in cisplatin-induced NCI-N87 cells, which were reversed by upregulating Nrf2. BAY-3827 (AMPK inhibitor) or p-nitro-Pifithrin-α (p53 inhibitor) treatments also reversed the effects of metformin increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. These results suggest that metformin significantly increases chemosensitivity of gastric cancer to cisplatin by inhibiting Nrf2 expression and metabolic reprogramming and activating oxidative stress and the pathway of p53 and AMPK.

Acinetobacter baumannii is known for its ability to invade and persist within eukaryotic cells, impacting infection outcomes and disease progression. This study investigates the role of Omp34, a key outer membrane protein (Omp), in A. baumannii interaction with epithelial cells and the protective effects of anti-Omp34 antibodies (Abs). Omp34 is a key regulator of A. baumannii epithelial cell invasion, influencing bacterial adherence, internalization, and intracellular proliferation. The presence of anti-Omp34 Abs mitigates A. baumannii-induced cellular damage and enhances bacterial clearance. The process involved the expression and purification of Omp34, which in turn induced Abs in BALB/c mice against Omp34. The acute toxicity of Omp34 was studied through a histological analysis conducted on six distinct organs in mice. HeLa cells were infected by A. baumannii ATCC 19606 and a clinical strain. Various aspects of A. baumannii behavior with HeLa cells, including HeLa cell viability, adherence, serum resistance, cell internalization, and intracellular proliferation with and without anti-Omp34 sera. Cytoskeleton inhibitors were used to study the potential roles played in the process of A. baumannii invasion by microfilaments and microtubules. Omp34 effectively triggered Ab production in mice without resulting in any toxicity. The assay for serum resistance revealed potent bactericidal and antibiofilm effects on both A. baumannii strains. Bacterial internalization was constrained when actin polymerization was inhibited. Examination under the microscope revealed instances of adherence, alterations in the cell membrane, apoptosis, vacuolization, and cell damage. HeLa cells exposed to anti-Omp34 serum showed decreased cell damage. The results provide substantial evidence of the adherence capacity of A. baumannii to proliferate in the epithelial cells. In conclusion, Omp34 plays a substantial role in regulating interactions between epithelial cells and A. baumannii, the multifaceted nature of which intricately modifies the trajectory of infection within host cells by A. baumannii.

Immediately after injury, damaged cells elicit tissue regeneration, a healing process that enables optimal renewal and regrowth of injured tissues. Results obtained in a large number of experimental studies suggested that the cross talk between pericytes, mesenchymal stem cells (MSC), tissue-resident stem cells, and immune cells has a crucially important role in the regeneration of injured tissues. Pericytes, MSCs, and immune cells secrete bioactive factors that influence each other's behavior and function. Immune cells produce inflammatory cytokines and chemokines that influence pericytes' migration, proliferation, and transition to MSC. MSC releases immunoregulatory factors that induce the generation of immunosuppressive phenotype in inflammatory immune cells, alleviating detrimental immune responses in injured tissues. MSC also produces various growth factors that influence the differentiation of tissue-resident stem cells into specific cell lineages, enabling the successful regeneration of injured tissues. A better understanding of molecular mechanisms that regulate crosstalk between pericytes, MSC, and immune cells in injured tissues would enable the design of new therapeutic approaches in regenerative medicine. Accordingly, in this review paper, we summarized current knowledge related to the signaling pathways that are involved in the pericytes' activation, pericytes-to-MSC transition, differentiation of tissue-resident stem cells, and MSC-dependent modulation of immune cell-driven inflammation, which are crucially responsible for regeneration of injured tissues.

Oxidative stress, a widespread phenomenon involved in many pathological conditions, may be closely related with the progression of oral leukoplakia (OLK). Under chronic inflammation, oxidative stress could stimulate the local formation of a tumor-specific microenvironment in some types of cancer, though not well defined in oral cancer even in OLK. Peroxiredoxin 1 (Prx1), a widely expressed sulfhydryl antioxidant protein, is overexpressed in various tumors and affects tumorigenesis, cell proliferation, apoptosis, invasion, and metastasis. Prx1 also acts as a potent proinflammatory factor. Nuclear factor (NF)-κB is a member of the core dimeric transcription factor family that coordinates the inflammatory response. To investigate the role of Prx1 in oxidative stress-related inflammation in OLK, a coculture model of human dysplastic oral keratinocyte (DOK) and human epidermal fibroblast (HFF) was established and stimulated with H₂O₂. Cellular reactive oxygen species (ROS) and Prx1 levels in DOK were determined via flow cytometry and western blotting, respectively. Additionally, the levels of the inflammatory factors, interleukin (IL)-6, IL-8, IL-10, and interferon (IFN)-γ, in the conditioned medium were determined via enzyme-linked immunosorbent assay (ELISA). DOK nuclear expression of NF-κB was detected via immunofluorescence assay and western blotting. Moreover, the expression levels of inflammatory factors and the nuclear expression of NF-κB were examined in 4-nitroquinoline-1-oxide (4NQO)-induced tongue precancerous tissues of mice. H₂O₂ increased Prx1 levels and nuclear expression levels of NF-κB in DOKs and mouse tongue precancerous tissues and elevated the levels of IL-6, IL-8, IL-10, and IFN-γ secreted in the culture supernatants and mouse tongue tissues. However, Prx1 knockdown in DOK and mouse tongue tissues attenuated the upregulation of inflammatory factor and nuclear NF-κB expression levels. Overall, our results suggest that oxidative stress increases Prx1 expression, which promotes inflammatory factor expression by activating NF-κB in human DOK and mouse tongue precancerous tissues.