Hasil untuk "Pathology"

Yang Shi, Kaoru Yamada, S. A. Liddelow et al.

Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani et al.

Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished—training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer’s pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology. Peripheral stimuli can induce acute immune training and tolerance in the brain and lead to long-lasting epigenetic reprogramming of microglia; these changes alter pathology in mouse models of stroke and Alzheimer’s pathology .

R. Nixon, J. Wegiel, Asok Kumar et al.

Yoshinori Kawagoe

J. Spurlock

Taha Masoudsinaki, Shima Hadifar, Hamzeh Sarvnaz et al.

Abstract Leishmaniasis is a vector-borne infectious disease that affects many subtropical countries. Leishmania (L.) major and L. tropica are among the old-world causative agents and cause cutaneous leishmaniasis (CL). The parasite utilizes various mechanisms to evade host immune responses and facilitate intracellular survival. Among these mechanisms, apoptosis inhibition through altering the host cell miRNA expression profile plays a significant role in parasite survival and infection progression. Based on the in-silico analysis through the miRDB database and literature review, miR-4795-3p, miR-6785-5p, miR-5011-5p, and miR-155-5p were selected as miRNAs regulating apoptosis-related genes. The expression of selected miRNAs was evaluated in the skin biopsy lesions collected from L. tropica and L. major-infected patients by qRT-PCR. Our results showed that miR-155-5p, miR-5011-5p, and miR-6785-5p were significantly upregulated (P < 0.05) in L. tropica-infected patients. Similar expression patterns for miR-155-5p and miR-6785-5p, but with a higher magnitude, were found in the lesions of CL patients infected with L. major. Additionally, miR-4795-3p expression level was downregulated in this group. The KEGG pathway analysis indicated that these miRNAs target several pathways that play key roles during leishmaniasis. The results underscore that further investigation is needed to better understand the regulatory roles of these miRNAs in CL infection.

Menglin Cong, Shufeng Li, Yu Fu et al.

Abstract Osteosarcoma (OS) is the most common primary bone malignancy because of its extra high tendency of metastasis. In-depth research is needed to uncover the pathogenesis of patients with OS cells. We collected 74 tissue samples from patients with OS cells and measured the expression levels of ghrelin by immunohistochemistry. Ghrelin was added into OS cell lines in CCK8 assays, JC-1 staining and Western blot analysis were performed to explore its effect on the aggressiveness of OS cells and drug resistance. To determine its function, ghrelin was overexpressed or knocked down in OS cells and then detect cell proliferation in the xenograft mouse model and orthotopic model. Western blot analysis was performed to explore ghrelin-regulated signal pathways. In this work, we identified the relation between the level of ghrelin expression and poor prognosis of OS patients. As well as promoting proliferation, migration, and invation, ghrelin promotes the survival of OS in vitro as well as in vivo, and reduces the apoptosis of OS cells. What’s more, ghrelin increases the resistance of cis-platinum by changing mitochondrial function and decreases the expression of MDR-1. Above all, these results demonstrated ghrelin exerts tumorigenic and metastatic effects and may be a potential therapeutic target.

Nayoung Ryoo, Ji Yong Park, Chunghwee Lee et al.

Abstract Background Subjective cognitive decline (SCD) has been recognized as a preclinical stage of Alzheimer’s disease. However, the identification of early functional brain changes remains challenging. This study investigated the functional brain changes in SCD using longitudinal EEG and evaluate the feasibility of EEG features as scalable biomarkers for identifying amyloid burden and cognitive decline using an interpretable machine learning framework. Methods We analyzed 120 individuals with SCD enrolled in a multicenter prospective cohort (the CoSCo study) at baseline and after a 2-year follow-up. Participants were classified as amyloid-positive (A + SCD) or amyloid-negative (A − SCD). Spectral power and graph theory-based network analyses were conducted. Also, we trained machine learning classifiers to distinguish between the groups and interpreted the predictions of classifiers using SHAP. Results At both baseline and follow-up, the A + SCD group exhibited elevated low-frequency (delta and theta) activity and reduced alpha activity compared to the A − SCD group. The EEG-based classifiers distinguished A + SCD from A-SCD individuals with high performance, outperforming a classifier based on demographic data. The results of SHAP analysis confirmed the importance and relative contribution of selected EEG features. Conclusions Longitudinal EEG, when combined with interpretable machine learning, can detect and track the functional alterations of brain related to amyloid pathology in preclinical AD. Our findings support the feasibility of EEG as a non-invasive, scalable, and sensitive biomarker for risk stratification, before overt cognitive impairment emerges. Trial registration This study was registered at the Clinical Research Information Service (CRIS) (cris.nih.go.kr/cris; # KCT0003397, Registration Date: December 21, 2018).

András Drozgyik, Noémi Kránitz, Tamás Szabó et al.

<b>Background:</b> Accurate orientation of resected breast specimens is essential for proper pathological evaluation and margin assessment. Misorientation may compromise analysis, lead to imprecise re-excisions, and increase the risk of local recurrence. This study aims to evaluate a novel specimen plate designed to maintain consistent tissue orientation and compares its effectiveness to traditional suture marking. <b>Methods:</b> In a single-center, prospective, randomized two-arm trial, 56 specimens were oriented with the new plate and 54 with conventional sutures. Outcomes included intraoperative imaging interpretation, specimen handling, and pathological assessment, with a focus on orientation accuracy and margin evaluation. <b>Results:</b> The specimen plate significantly reduced misorientation (<i>p</i> < 0.01) and improved interpretation during intraoperative imaging. Pathologists reported greater ease in identifying direction and tumor-free zones, leading to a more accurate margin assessment. Non-R0 resections requiring re-excision were fewer with the specimen plate (8.9%) compared to suture marking (22.2%). <b>Conclusions:</b> The newly developed specimen plate can offer a reliable solution for improving specimen orientation in breast cancer surgery; however, further validation in multicenter studies is needed to confirm its applicability across diverse surgical settings. By ensuring consistent orientation and enhancing diagnostic interpretation, it may help reduce re-excisions and improve patient safety.

Peter C. Burger, Bernd W. Scheithauer, F. Vogel

Løseth Sissel, Nebuchennykh Maria, Brokstad Ruth Therese et al.

We aimed to investigate to what extent small fiber tests were abnormal in an unselected retrospective patient material with symptoms suggesting that small fiber neuropathy (SFN) could be present, and to evaluate possible gender differences.

Amal F. Makled, Sahar A. M. Ali, S. S. Eldahdouh et al.

Introduction. The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results. The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784–52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673–81.249), both p<0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p<0.001). Conclusion. ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.

Xue-qian Qian, Li-li Chen, Chang-kun Zhu et al.

ObjectiveMalignant transformation of mature ovarian teratoma is a rare phenomenon, mainly occurring in postmenopausal period. Squamous cell carcinoma accounts for 80% of all malignant transformations. Sarcoma transformation is much less common and tends to imply a poorer prognosis and aggressiveness.Case reportWe report a case of undifferentiated sarcoma with squamous cell carcinoma in a mature cystic teratoma of the ovary in a 36-year-old woman. The tumor shows epithelial and stromal components. This is a unique report of a benign teratoma of the ovary with malignant transformation, showing epithelial and sarcomatous components. This young woman presented with abdominal distension and a rapidly enlarging ovario-derived pelvic mass with a slightly elevated CA199 tumor marker of 115.9 U/ml. The woman underwent transabdominal excision of the left ovarian cyst on October 20, 2020. During the operation, rapid freezing pathological examination did not indicate malignancy. The postoperative paraffin pathology revealed undifferentiated sarcoma with squamous cell carcinoma (from mature cystic teratoma malignancy), and she finally received comprehensive staging surgery. Postoperative paraffin pathology showed no residual cancer in uterus and other tissues, and all lymph nodes were negative. The patient was finally diagnosed with ovarian malignant tumor IC1 stage (high-grade spindle cell sarcoma complicated with squamous cell carcinoma). Chemotherapy was completed three times after surgery, and no signs of recurrence were found after follow-up.ConclusionThe preoperative diagnosis and intraoperative rapid freezing examination of malignant transformation of mature teratoma of ovary are challenging.

R. Macsween

Ying Liu, Maryam Shahi, Karin Miller et al.

Diagnosis of pelvic gastrointestinal stromal tumors (GISTs) can be challenging because of their nonspecific presentation and similarity to gynecological neoplasms. In this series, we describe the clinicopathological features of 20 GIST cases: 18 patients presented with pelvic mass and/or abdominal pain concerning gynecological disease; 2 patients presented with a posterior rectovaginal mass or an anorectal mass. Total abdominal hysterectomy and/or salpingo-oophorectomy (unilateral or bilateral) were performed in 13 cases. Gross and histological examination revealed that the ovary/ovaries were involved in three cases, the uterus in two cases, the vagina in two cases and the broad ligament in one case. Immunohistochemically, all tumors (20/20, 100%) were diffusely immunoreactive for c-KIT. The tumor cells were also diffusely positive for DOG-1 (10/10, 100%) and displayed focal to diffuse positivity for CD34 (11/12, 92%). Desmin was focally and weakly expressed in 1 of the 14 tested tumors (1/14, 7%), whereas 2 of 8 tumors (2/8, 25%) showed focal SMA positivity. At the molecular level, 7 of 8 (87.5%) GISTs with molecular analysis contained <i>c-KIT</i> mutations with the second and third <i>c-KIT</i> mutations detected in some recurrent tumors. In addition to <i>c-KIT</i> mutation, a pathogenic <i>RB1</i> mutation was detected in two cases. We extensively discussed these cases focusing on their differential diagnosis described by the submitting pathologists during consultation. Our study emphasizes the importance of precision diagnosis of GISTs. Alertness to this entity in unusual locations, in combination with clinical history, morphological features as well as immunophenotype, is crucial in leading to a definitive classification.

C. Savage, C. Winearls, D. Evans et al.

A. Scull

Will reading habit influence your life? Many say yes. Reading difference and pathology stereotypes of sexuality race and madness is a good habit; you can develop this habit to be such interesting way. Yeah, reading habit will not only make you have any favourite activity. It will be one of guidance of your life. When reading has become a habit, you will not make it as disturbing activities or as boring activity. You can gain many benefits and importances of reading.

Alison E. Smith, Emanuela Ferraro, Anton Safonov et al.

Resistance to HER2 inhibition in HER2- amplified breast cancer is common in the metastatic setting and the underlying molecular mechanisms remain unknown. Here, the authors, perform genomic profiling of 733 HER2-amplified breast cancers and propose genetic activation of MAPK as a resistance mechanism.

Han Shin Lee, Hee Jeong Kim, Il Yong Chung et al.

Abstract We used 3D printed-breast surgical guides (3DP-BSG) to designate the original tumor area from the pre-treatment magnetic resonance imaging (MRI) during breast-conserving surgery (BCS) in breast cancer patients who received neoadjuvant systemic therapy (NST). Targeting the original tumor area in such patients using conventional localization techniques is difficult. For precise BCS, a method that marks the tumor area found on MRI directly to the breast is needed. In this prospective study, patients were enrolled for BCS after receiving NST. Partial resection was performed using a prone/supine MRI-based 3DP-BSG. Frozen biopsies were analyzed to confirm clear tumor margins. The tumor characteristics, pathologic results, resection margins, and the distance between the tumor and margin were analyzed. Thirty-nine patients were enrolled with 3DP-BSG for BCS. The median nearest distance between the tumor and the resection margin was 3.9 cm (range 1.2–7.8 cm). Frozen sections showed positive margins in 4/39 (10.3%) patients. Three had invasive cancers, and one had carcinoma in situ; all underwent additional resection. Final pathology revealed clear margins. After 3-year surveillance, 3/39 patients had recurrent breast cancer. With 3DP-BSG for BCS in breast cancer patients receiving NST, the original tumor area can be identified and marked directly on the breast, which is useful for surgery. Trial Registration: Clinical Research Information Service (CRIS) Identifier Number: KCT0002272. First registration number and date: No. 1 (27/04/2016).