Hasil untuk "Pathology"

John L. Robinson, Eddie B. Lee, S. Xie et al.

Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-β, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72). Each group was divided into subgroups without or with co-pathologies. Age and sex matched logistic regression models compared co-pathology prevalence between groups. Co-pathology prevalence was similar between the minimal pathology group and most neurodegenerative diseases for each proteinopathy: tau was nearly universal (92-100%), amyloid-β common (20-57%); α-synuclein less common (4-16%); and TDP-43 the rarest (0-16%). In several neurodegenerative diseases, co-pathology increased: in Alzheimer's disease, α-synuclein (41-55%) and TDP-43 (33-40%) increased; in progressive supranuclear palsy, α-synuclein increased (22%); in corticobasal disease, TDP-43 increased (24%); and in neocortical Lewy body disease, amyloid-β (80%) and TDP-43 (22%) increased. Total co-pathology prevalence varied across groups (27-68%), and was increased in high Alzheimer's disease, progressive supranuclear palsy, and neocortical Lewy body disease (70-81%). Increased age at death was observed in the minimal pathology group, amyotrophic lateral sclerosis, and multiple system atrophy cases with co-pathologies. In amyotrophic lateral sclerosis and neocortical Lewy body disease, co-pathologies associated with APOE ɛ4. Lewy body disease cases with Alzheimer's disease co-pathology had substantially lower Mini-Mental State Examination scores than pure Lewy body disease. Our data imply that increased age and APOE ɛ4 status are risk factors for co-pathologies independent of neurodegenerative disease; that neurodegenerative disease severity influences co-pathology as evidenced by the prevalence of co-pathology in high Alzheimer's disease and neocortical Lewy body disease, but not intermediate Alzheimer's disease or limbic Lewy body disease; and that tau and α-synuclein strains may also modify co-pathologies since tauopathies and synucleinopathies had differing co-pathologies and burdens. These findings have implications for clinical trials that focus on monotherapies targeting tau, amyloid-β, α-synuclein and TDP-43.

A. Kapasi, C. DeCarli, J. Schneider

Shuxin Li, Yongliang Qu, Yongshuai Huang et al.

Ectopic adrenal tissue refers to adrenal tissue appearing in an abnormal anatomical location, typically originating from residual adrenal tissue or ectopic structures during embryonic development. As a rare congenital anomaly, its atypical anatomical position and diverse clinical manifestations often pose diagnostic challenges. This report describes a 46-year-old male patient who presented with intermittent hematuria for two weeks. Enhanced CT of the kidneys revealed a protruding nodule at the margin of the right renal pole, measuring approximately 1.6 cm and showing relatively uniform enhancement, suggesting a hypo vascular mass lesion. Enhanced MRI of both kidneys showed a nodule at the right renal pole, consistent with a mass due to insufficient blood supply. Based on imaging findings and clinical symptoms, a preliminary diagnosis of right renal carcinoma (RCC) was made, leading to a laparoscopic partial nephrectomy. Postoperative pathology confirmed the lesion as ectopic adrenal tissue. This case highlights that ectopic adrenal tissue within the kidney may mimic renal cell carcinoma in both clinical presentation and imaging characteristics, underscoring the need for enhanced differential diagnosis between these two conditions in clinical practice.

Mohamed S. Kishta, Aya Khamis, Hafez AM et al.

Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy due to its high rates of recurrence, metastasis, and resistance to conventional therapies. microRNA-200c (miRNA-200c) has emerged as a critical tumor suppressor in HNSCC, with the potential to inhibit epithelial-mesenchymal transition (EMT), which is considered as a key process in cancer metastasis and progression. Interestingly, there are also controversial findings in HNSCC characterizing miRNA-200c as oncogenic factor. This review article provides a comprehensive overview of the current understanding of miRNA-200c's general role in cancer, and particularly in HNSCC, highlighting its mechanisms of action, including the regulation of EMT and other oncogenic pathways.Additionally, the review explores the innovative approach of exosome-mediated delivery of miRNA-200c as a therapeutic strategy. Exosomes, as natural nanocarriers, offer a promising vehicle for the targeted delivery of miRNA-200c to tumor cells, potentially overcoming the limitations of traditional delivery methods and enhancing therapeutic efficacy. The review also discusses the challenges and future directions in the clinical application of miRNA-200c, particularly focusing on its potential to improve outcomes for HNSCC patients. This article seeks to provide valuable insights for researchers and clinicians working towards innovative treatments for this aggressive cancer type.

Xiulan Xie, Jiasui Zhan, Maozhi Ren

ABSTRACT Human civilization is threatened by food insecurity and habitat loss owing to the cumulative effects of anthropogenic and natural factors. Thus, increasing food production while using fewer resources and exploring the potential of interstellar migration is essential. Particularly, microalgae can fulfil the biological, nutritional, and efficiency requirements of industrial food production on Earth and other potential planets. Herein, we discuss the industrial production of microalgae on Earth and in outer space, along with the technological advances that will help reshape the genetic and chemical properties of microalgae for better production, nutrition, and adaptation. We propose the concept of “multiplanetary farming” to address future requirements for agricultural development. This perspective review is intended to stimulate a broad debate and research on this paramount issue for the future of mankind.

Shanshan Bi, Yueguang Wu, Ning Ding et al.

Summary: Esophageal squamous cell carcinoma (ESCC) is a common malignancy, characterized by a multistep pathogenic process regulated spatiotemporally within the esophageal epithelial microenvironment, including vessel normalization and immune infiltration. However, empirical evidence elucidating esophageal vascular remodeling and immune infiltration during ESCC tumorigenesis in situ is lacking. In this study, utilizing a mouse model recapitulating progressive human ESCC stages, we established a tissue clearing workflow for three-dimensional visualization and analysis of esophageal vessels and T cell distribution. Through this workflow, we delineated the spatial dynamics of vascular remodeling, CD3+ T cells, and characteristic T cell aggregates employing high-resolution light-sheet fluorescence microscopy across five ESCC pathogenic stages. Vessel remodeling might be coupled with T cell infiltration, and their interactions predominantly occurred at the inflammatory stage. These findings provided insights into research methodologies of esophageal cancer and spatiotemporal landscapes of vascular and T cell during ESCC initiation and progression.

Amanda S. Latham, Amanda S. Latham, Julie A. Moreno et al.

Neuroinflammation is a universal characteristic of brain aging and neurological disorders, irrespective of the disease state. Glial inflammation mediates this signaling, through astrocyte and microglial polarization from neuroprotective to neurotoxic phenotypes. Glial reactivity results in the loss of homeostasis, as these cells no longer provide support to neurons, in addition to the production of chronically toxic pro-inflammatory mediators. These glial changes initiate an inflammatory brain state that injures the central nervous system (CNS) over time. As the brain ages, glia are altered, including increased glial cell numbers, morphological changes, and either a pre-disposition or inability to become reactive. These alterations induce age-related neuropathologies, ultimately leading to neuronal degradation and irreversible damage associated with disorders of the aged brain, including Alzheimer’s Disease (AD) and other related diseases. While the complex interactions of these glial cells and the brain are well studied, the role additional stressors, such as infectious agents, play on age-related neuropathology has not been fully elucidated. Both biological agents in the periphery, such as bacterial infections, or in the CNS, including viral infections like SARS-CoV-2, push glia into neuroinflammatory phenotypes that can exacerbate pathology within the aging brain. These biological agents release pattern associated molecular patterns (PAMPs) that bind to pattern recognition receptors (PRRs) on glial cells, beginning an inflammatory cascade. In this review, we will summarize the evidence that biological agents induce reactive glia, which worsens age-related neuropathology.

Benjamin Krämer, Ansel P. Nalin, Feiyang Ma et al.

Summary: Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of “liver-type” ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-β1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

Takayuki KIKUCHI, Yasushi TAKAGI, Jyoji NAKAGAWARA et al.

Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had <85 in each index were 27.8%-33.3% in the WAIS-III and 16.7%-47.2% in the Wechsler Memory Scale-Revised. The group analysis of iomazenil SPECT demonstrated a decreased accumulation in the bilateral medial frontal areas in comparison with the normal control, whereas there were no specific characteristics on conventional imaging in the cohort. Iomazenil SPECT is a possible universal diagnostic method for the extraction of patients with cognitive impairment in MMD.

Fatemeh Atashi, Nafiseh Vahed, Parya Emamverdizadeh et al.

Head and neck cancers are highly prevalent worldwide. Most of these lesions are diagnosed in the advanced stages of the disease. Thus, they do not often have a good long-term prognosis. Like other cancer types, head and neck cancers are managed by surgery, radiotherapy, and chemotherapy. Despite significant advances in the treatment of oral squamous cell carcinoma (OSCC), physicians encounter several challenges in the course of treatment. Various mechanisms mediate the clinical responses of a certain cancer to medications. Thus, efficient treatment planning requires adequate knowledge about the genes involved in drug resistance and the evaluation of the frequency percentage of resistance. Several studies have evaluated the causes and frequency percentages of 5-fluorouracil (5-FU) and cisplatin resistance. In this systematic review, all the relevant articles published until November 30, 2019, were retrieved from the Scopus, Embase, Medline, ISI, Web of Science, and Cochrane databases using certain MeSH and EMTTree keywords. A total of 2164 articles were retrieved of which, 18 were included in the review since they had reported the frequency percentages of drug resistance. Of all, 10 articles had evaluated cisplatin (1317 samples). A meta-analysis of the results revealed a frequency of 33% for cisplatin resistance. Eight studies had evaluated 5-FU (476 samples). A meta-analysis of the results revealed a frequency of 40.2 % for 5-FU resistance. Overcoming cisplatin resistance or 5-FU resistance can significantly enhance recovery in advanced HNSCC. Attempts should be made to eliminate the cause and use multi-drug regimens to increase the success rate of treatment.

Javier Varas de la Fuente, Rosa Isabel Sánchez Alonso

Introducción: El trasplante de microbiota fecal se ha comenzado a utilizar como tratamiento de patologías intestinales como la infección por Clostridium Difficile. Dado su éxito en esta patología, se hace necesario investigar si también es efectivo en otras patologías intestinales y su grado de seguridad. Objetivo: encontrar evidencias actuales que demuestren la efectividad del trasplante de microbiota fecal en el tratamiento de la patología intestinal, mostrando tanto los beneficios potenciales para la salud como los efectos adversos si los hubiera. Método: Revisión bibliográfica en Medline a través de Pubmed, Biblioteca Cochrane, CINAHL y SciELO. Publicados entre 2014 y 2019. Ensayos clínicos, metaanálisis y revisiones sistemáticas. Se excluyeron los estudios que realizaron intervenciones concomitantes y los que trataran la infección por Clostridium Difficile. Evaluación de calidad mediante herramienta CASPe. Extracción manual de los resultados. Variables resultado: remisión clínica y endoscópica de la patología, alivio sintomático, efectos adversos graves. Resultados: Se encontraron 45 estudios primarios y 18 revisiones, de los que se seleccionaron 4 estudios primarios y 5 revisiones. Esta revisión proporciona evidencia de nivel medio a favor de la utilización del trasplante de microbiota fecal en el tratamiento de la enfermedad intestinal inflamatoria, la encefalopatía hepática y la constipación intestinal. No se encontraron resultados favorables a su uso en el tratamiento del síndrome del intestino irritable. ABSTRACT Introduction: Fecal microbiota transplantation has begun to be used as a treatment for intestinal pathologies such as Clostridium Difficile infection. Due to its success in this pathology, it is necessary to investigate if it is also effective in other intestinal pathologies and its degree of security. Objective: to find current evidences demonstrating the effectiveness of fecal microbiota transplantation in the treatment of intestinal pathology, showing both potential health benefits and adverse effects, if any. Method: Bibliographic review in Medline via Pubmed, Cochrane Library, CINAHL and SciELO. Published between 2014 and 2019. Clinical trials, meta-analysis and systematic reviews. Studies had been conducted concurrent interventions and those that treated Clostridium Difficile infection were excluded Quality assessment by CASPe tool. Manual removal of the results. Outcomes: Clinical and endoscopic remission, diversity of intestinal microbiota, serious adverse effects. Results: 45 primary studies and 18 reviews were found, of which 4 primary studies and 5 reviews were selected. This reviews provides midlevel evidence for use the fecal microbiota transplantation as treatment of inflammatory bowel disease, hepatic encephalopathy and intestinal constipation. No favorable results were found for its use as treatment of irritable bowel syndrome.

Layla M. Saleh, Nour Darwish, Sherin Abdel-Aziz et al.

Background: Overexpression of cytokine receptor-like factor 2 (CRLF2) caused by different genetic aberrations has been observed in acute lymphoblastic leukemia (ALL) and correlated with poor outcome. Most patients with high CRLF2 expression are clustered in the Philadelphia-like (Ph-like) ALL subgroup. Ph-like ALL is reported to be associated with alterations in IKZF1 gene, encoding the transcription factor Ikaros. Aim: To identify CRLF2 and IKZF1 alterations in Egyptian patients with ALL and to determine their prognostic significance. Methods: Peripheral blood samples from 34 newly diagnosed ALL patients treated at an Egyptian tertiary oncology center and 14 controls were assessed for CRLF2 and IKZF1 mRNA expression using real-time polymerase chain reaction. Results: CRLF2 was significantly overexpressed in ALL patients compared to controls (p = 0.038). The response to treatment was significantly better in patients with low CRLF2 expression (p = 0.029). The rate of remission, relapse and induction death was 82%, 12% and 6% in the low CRLF2 expression group and 41%, 18% and 41% in the high expression one. Overall survival was significantly shorter among ALL with high CRLF2 (p = 0.034). IKZF1 expression level did not differ significantly between patients and controls. Patients with low IKZF1 exhibited significantly higher leucocytic count and lower platelet count (p = 0.038 and 0.044, respectively). IKZF1 overexpression did not correlate significantly with response to treatment or survival. Conclusion: High CRLF2 expression was associated with poor outcome among ALL patients. Further research is needed to improve the diagnostic and therapeutic approaches in ALL patients with poor prognosis.

Nina V. Fedorova, Natalia V. Zhurkova, Nato D. Vashakmadze et al.

Background. Type II mucolipidosis (I-cell disease, ICD) is one of the lysosomal storage diseases. It is very rare disease; the literature describes only few cases with confirmed diagnosis of mucolipidosis. Cardiovascular changes in children with such pathology are even less often. Clinical case description. The article describes the clinical case of type II mucolipidosis alongside with cardiovascular pathology — valvular heart apparatus defect with abdominal aortic hypoplasia and reversible myocardial dysfunction on the therapy of chronic heart failure (CHF). The patient has coarse face, gingival hyperplasia, macroglossia, dysostosis multiplex, diffuse muscular hypotonia, and mass of subcutaneous tissue. Arterial hypertension, heart cavities dilatation, left ventricular (LV) walls hypertrophy, and data of CT aortography let us to diagnosis abdominal aortic hypoplasia. Conclusion. Cardiovascular malformation in patients with mucolipidosis leads to severe, life-threatening conditions development. Untimely diagnosis can worsen the course of disease. Multidisciplinary approach is needed for the patient management.

Maria Lytrivi, Kassem Ghaddar, Miguel Lopes et al.

Abstract Background Prolonged exposure to elevated free fatty acids induces β-cell failure (lipotoxicity) and contributes to the pathogenesis of type 2 diabetes. In vitro exposure of β-cells to the saturated free fatty acid palmitate is a valuable model of lipotoxicity, reproducing features of β-cell failure observed in type 2 diabetes. In order to map the β-cell response to lipotoxicity, we combined RNA-sequencing of palmitate-treated human islets with iTRAQ proteomics of insulin-secreting INS-1E cells following a time course exposure to palmitate. Results Crossing transcriptome and proteome of palmitate-treated β-cells revealed 85 upregulated and 122 downregulated genes at both transcript and protein level. Pathway analysis identified lipid metabolism, oxidative stress, amino-acid metabolism and cell cycle pathways among the most enriched palmitate-modified pathways. Palmitate induced gene expression changes compatible with increased free fatty acid mitochondrial import and β-oxidation, decreased lipogenesis and modified cholesterol transport. Palmitate modified genes regulating endoplasmic reticulum (ER) function, ER-to-Golgi transport and ER stress pathways. Furthermore, palmitate modulated cAMP/protein kinase A (PKA) signaling, inhibiting expression of PKA anchoring proteins and downregulating the GLP-1 receptor. SLC7 family amino-acid transporters were upregulated in response to palmitate but this induction did not contribute to β-cell demise. To unravel critical mediators of lipotoxicity upstream of the palmitate-modified genes, we identified overrepresented transcription factor binding sites and performed network inference analysis. These identified LXR, PPARα, FOXO1 and BACH1 as key transcription factors orchestrating the metabolic and oxidative stress responses to palmitate. Conclusions This is the first study to combine transcriptomic and sensitive time course proteomic profiling of palmitate-exposed β-cells. Our results provide comprehensive insight into gene and protein expression changes, corroborating and expanding beyond previous findings. The identification of critical drivers and pathways of the β-cell lipotoxic response points to novel therapeutic targets for type 2 diabetes.

May-Jen Huang, Yu-Cheng Lin, Kevin Liu et al.

Background: We found that Taiwanese adults carrying genotypes of UDP-glucuronosyltransferase (UGT) 1A1 with enzyme activity ≤40% of normal were at high risk for developing Gilbert's syndrome. However, the relationship between UGT1A1 activity and neonatal hyperbilirubinemia has never been evaluated for Taiwanese. Methods: We enrolled 141 hyperbilirubinemic neonates partially fed supplementary infant formula and 432 controls; and 112 hyperbilirubinemic neonates exclusively breastfed and 493 controls. The five single nucleotide polymorphisms (SNPs) at nucleotides −53, 211, 686, 1091 and 1456 in the UGT1A1 gene were determined and UGT1A1 activity was estimated. Odds ratios (ORs) of variation status in the UGT1A1 gene and enzyme activity for the development of neonatal hyperbilirubinemia were calculated, respectively. Results: For neonates partially fed supplementary infant formula, the adjusted OR (AOR) for the development of hyperbilirubinemia was significantly higher in the neonates carrying the homozygous variation (211AA) in the UGT1A1 gene than for those carrying the wild type (AOR = 6.00, p < 0.001). Only the AOR of those carrying UGT1A1 activity ranked 31–40% of normal was statistically significant (AOR = 3.16, p < 0.001). For the hyperbilirubinemic neonates exclusively breastfed, AOR for the development of hyperbilirubinemia is positively correlated to degree of variation (AOR = 1.95, 2.19 and 4.53; with p = 0.003, 0.05 and < 0.001, respectively), while the effect of UGT1A1 enzyme activity was varied (AOR = 1.02–3.72, with p = 0.95∼<0.001). Conclusion: The estimated enzyme activity depending on combination of SNPs (genotypes) in the UGT1A1 gene could not be utilized to explain the development of neonatal hyperbilirubinemia. We reconfirm that the −53 A(TA)7TAA/A(TA)7TAA is not, while the 211AA is a risk factor for the development of neonatal hyperbilirubinemia in Taiwanese.

J. McCord, I. Fridovich

Alberto Maria Saibene, Cecilia Rosso, Paolo Castellarin et al.

Abstract Purpose Because of its affinity for water-based tissues, carbon dioxide (CO2) laser has become an instrument of choice for treating oral mucosa conditions, ranging from inflammatory to malignant lesions. The aim of this work is to systematically evaluate the outcomes of laser surgery over a wide range of lesions, while providing a solid and reproducible protocol for CO2 laser surgery in the outpatient management of oral lesion. Methods Seventy-eight patients underwent 92 laser outpatient procedures for treatment of a wide range of benign and malignant lesions. We performed 60 removals, 11 exeretic biopsies, 15 vaporizations, and 3 vaporization/removal combined. We analyzed laser parameters applied for each technique and provided a systematic evaluation of surgical results. Results No problems occurred intraoperatively in any of the patients. Five patients complained marginal pain, while 3 patients had postsurgery bleeding. All treatments were successful, with the notable exception of 3 relapsing verrucous proliferative leukoplakias and an infiltrating squamous cell carcinoma of the tongue requiring radicalization. We did not record any adverse reactions to drugs or lesions due to laser action. Concordance between clinical diagnosis and pathology results was at 94.8%. Conclusions Our data indicate that CO2 laser is a solid choice for outpatient treatment of oral lesions. This technique grants painless and almost bloodless treatment, with negligible recurrence rates. Providing a solid reference for laser settings and operative techniques could provide a foundation for further exploring this tool while offering the basis for a positive comparison between different surgical techniques and options.

H. Powell, P. Lampert

Aled J. Parry, Matthew Hoare, Dóra Bihary et al.

Notch can drive senescence in a cell contact dependent manner. Here the authors show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously via the JAG1-NOTCH-HMGA1 interplay during senescence.

G. Slavin