Hasil untuk "Cytology"

Kwangsup Lee, Chansik Nam, Taejung Dan et al.

A 10-year-old intact female Bichon Frise presented with multiple firm skin nodules on all four limbs. The nodules progressively increased in number and size over seven months. Diagnostic tests included cytology of fine-needle aspirates, histopathology of skin biopsies, radiography, and abdominal ultrasonography. Cytology revealed spindle-shaped mesenchymal cells and extracellular matrix components, and histopathology confirmed ND characterized by mature collagen deposition without evidence of malignancy. Ultrasonography detected multiple kidney cysts bilaterally, although their exact nature (benign or malignant) could not be confirmed histologically. Genetic analysis was performed, revealing no mutation in the traditionally implicated FLCN gene but multiple nonsynonymous mutations in the BRCA2 gene. This case suggests a potential association between BRCA2 gene mutations and the development of ND with renal cystic lesions, broadening the known genetic causes beyond the commonly reported FLCN mutation. Regular genetic screening and close monitoring of dermatological and renal conditions in atypical breeds are recommended. To the best of current knowledge, this is the first case report demonstrating ND and renal cysts associated with BRCA2 mutations in a Bichon Frise.

Agostina Longo, Valeria Manganelli, Roberta Misasi et al.

Autophagy and apoptosis are two essential mechanisms regulating cell fate. Although distinct, their signaling pathways are closely interconnected through various crosstalk mechanisms. Lipid rafts are described to act as both physical and functional platforms during the early stages of autophagic and apoptotic processes. Only recently has a role for lipid raft-associated molecules in regulating EV biogenesis and release begun to emerge. In particular, lipids of EV membranes are essential components in conferring stability to these vesicles in different extracellular environments and/or to facilitate binding or uptake into recipient cells. In this review we highlight these aspects, focusing on the role of lipid molecules during apoptosis and secretory autophagy pathways. We describe the molecular machinery that connects autophagy and apoptosis with vesicular trafficking and lipid metabolism during the release of EVs, and how their alterations contribute to the development of various diseases, including autoimmune disorders and cancer. Overall, these findings emphasize the complexity of autophagy/apoptosis crosstalk and its key role in cellular dynamics, supporting the role of lipid rafts as new therapeutic targets.

Shuvechha Chakraborty, Indumathi Palanikumar, Yash Gune et al.

Abstract Candida albicans, responsible for approximately 70% of all Candida infections, is a leading cause of invasive candidiasis and poses a significant global health threat. With the emergence of drug-resistant strains, mortality rates have reached a staggering 63.6% in severe cases, complicating treatment options and demanding the discovery of novel therapeutic targets. To address this pressing need, using a unique multidisciplinary approach, we attempted to identify some the critical metabolic pathways that can be targeted to modulate the virulence of CAL. Condition-specific genome-scale metabolic models (GSMMs), along with a novel integrated host-CAL model developed in this study, highlighted the central role of arginine (Arg) metabolism and uncovered ALT1, an arginine biosynthesis enzyme, as a critical metabolic vulnerability in CAL virulence. Heightened expression of arginine biosynthesis genes indicated that increased arginine synthesis mainly occurred through proline intermediates during host interaction. Significantly impaired virulence and in vivo pathogenicity of ALT1-deleted CAL highlighted the potential of targeting arginine metabolism as a novel strategy to combat antifungal resistance and underscored the power of integrating systems biology with experimental approaches in identifying new therapeutic targets.

Sonia M. Rocha-Sanchez, Elton Jeffrey North, Lilian E. Calisto et al.

No pharmacological interventions exist that can restore or preserve auditory function in the mammalian cochlea. Auditory hair cells (HCs) do not spontaneously regenerate, leading to permanent hearing loss. In non-mammalian vertebrates, HC regeneration happens through proliferation and differentiation of their clonally related supporting cells (SCs). The present study supports the potential of quinoxaline (Qx), a nonsteroidal anti-inflammatory compound, to stimulate SC proliferation in the auditory sensory epithelium, a process that may prime the tissue for future HC regeneration. We synthesized a series of Qx derivatives by introducing various substitutions, ranging from hydrophilic to lipophilic. Seventy analogs were generated and tested in vitro and in vivo. Among those, only one (Qx-100) exhibited the best medicinal chemistry profile and was further modified to expand the structure–activity relationship of the chemotype, develop additional analogs, and optimize potency, bioavailability, and in vivo efficacy. Ten new lead variants were generated. Of those, Qx-294 and Qx-301 demonstrated promising in vitro Absorption, Distribution, Metabolism, and Excretion (ADME) profiles and were selected for further testing. Overall, both compounds were rapidly absorbed in zebrafish and mice and promoted cell proliferation in vitro and in vivo without signs of apoptosis, supporting their potential for sensory HC regeneration.

Fahd Mohamed, Lenon DSouza, Mahesh Mijar

Purpose The aim of the study was to evaluate the role of music in alleviating anxiety in patients undergoing image guided procedures. Materials and Methods A total of 129 patients were included in this prospective study after obtaining clearance from the Institutional Ethics Committee. Patients were randomized into control (n = 59, median age 46, 30 males) and music (n = 70, median age 46.5, 33 males) groups. Procedures included thoracocentesis, paracentesis, fine needle aspiration cytology and biopsies of the breast, liver, thyroid and lymph nodes. It was performed over a period of 4 months, between September 2020 and December 2020. Pre- and intra procedure recordings of systolic blood pressure, diastolic blood pressure and heart rate were recorded. Circumstantial anxiety was evaluated using the Spielberg State-Trait Anxiety Inventory before and after the procedure. Results There was a statistically significant reduction (p = 0.001) in the rise of systolic blood pressure, diastolic blood pressure and heart rate in the music group as compared to the control group. There was also a statistically significant reduction (p = 0.001) in the State-Trait Anxiety Inventory scale values in the music group as compared to the control group during the procedure. Conclusion Patients undergoing image-guided procedures may be offered a choice to listen to music of their preference to reduce situational anxiety.

Giulia Dodi, Paola Di Filippo, Francesca Ciarelli et al.

A Nasal Provocation Test allows the differentiation of allergic and non-allergic rhinitis, but it is difficult and expensive. Therefore, nasal cytology is taking hold as an alternative. We carried out a cross-sectional study, including 29 patients with persistent rhinitis according to ARIA definition and negative skin prick tests. Nasal symptoms were scored from 0 to 5 using a visual analogue scale, and patients underwent blood tests to investigate blood cell count (particularly eosinophilia and basophilia), to analyze serum total and specific IgE and eosinophil cationic protein (ECP), and to perform nasal cytology. We performed a univariate logistical analysis to evaluate the association between total serum IgE, serum eosinophilia, basophils, and ECP and the presence of eosinophils in the nasal mucosa, and a multivariate logistic model in order to weight the single variable on the presence of eosinophils to level of the nasal mucosa. A statistically significant association between serum total IgE levels and the severity of nasal eosinophilic inflammation was found (confidence interval C.I. 1.08–4.65, odds ratio OR 2.24, <i>p</i> value 0.03). For this reason, we imagine a therapeutic trial with nasal steroids and oral antihistamines in patients with suspected LAR and increased total IgE levels, reserving nasal cytology and NPT to non-responders to the first-line therapy.

R.N. Chougule, P.V. Deshmukh, P.E. Shelke et al.

Karyotypes of six Ipomoea and one Merremia species were studied. Chromosome counts of 2n = 30 for I. corymbosa, I. kotschyana, I. marginata f. candida and M. rhyncorhiza) and 2n = 60 for I. ochracea were observed for the first time. Meiotic course of five Ipomoea species was also examined for the first time and two counts, i.e. n = 15 and n = 30 were recorded. Meiosis was found normal. Karyotypes of the studied species exhibited uniformity. All the species had chromosomes with median region centromeres and karyotypes were symmetrical (Stebbins’ 4A category). I. marginata f. candida had the shortest chromosomes with mean length of 0.99 ± 0.02 µm. I. ochracea and I. corymbosa had the longest chromosomes with mean length of 1.22 ± 0.05 µm and 1.22 ± 0.01 µm, respectively. As chromosomes were small and exhibited uniform morphology, fluorescent banding or fluorescent in-situ hybridization can be useful to differentiate the karyotypes and understand species interrelationships.

Lingzhi Li, Ping Liu, Rongliang Wang et al.

Understanding asymptomatic moyamoya disease (aMMD), for which treatment options are currently limited, is key to the development of therapeutic strategies that will slow down the progression of this disease, as well as facilitate the discovery of therapeutic targets for symptomatic MMD. Newly found transfer RNA-derived small RNAs (tsRNAs) perform potential regulatory functions in neovascularization, which is a well-known pathological manifestation of MMD. In this study, the neutrophilic tsRNA transcriptome in aMMD was profiled using next-generation RNA sequencing in five patients and five matched healthy subjects. A negative binominal generalized log-linear regression was used to identify differentially expressed (DE)-tsRNAs in aMMD. Gene Ontology and functional pathway analyses were used to identify biological pathways involved with the targeted genes of the DE-tsRNAs. Four tsRNAs were selected and validated using quantitative reverse transcription polymerase chain reaction. In total, 186 tsRNAs were DE between the two groups. Pathophysiological events, including immune response, angiogenesis, axon guidance, and metabolism adjustment, were enriched for the DE-tsRNAs. The expression levels of the four DE-tsRNAs were consistent with those in the neutrophilic transcriptome. These aberrantly expressed tsRNAs and their targeted pathophysiological processes provide a basis for potential future interventions for aMMD.

Jeeyoung Lee, Ly Thi Huong Luu Le, Eunkyoung Kim et al.

Cellular stress induces the formation of membraneless protein condensates in both the nucleus and cytoplasm. The nucleocytoplasmic transport of proteins mainly occurs through nuclear pore complexes (NPCs), whose efficiency is affected by various stress conditions. Here, we report that hyperosmotic stress compartmentalizes nuclear 26S proteasomes into dense nuclear foci, independent of signaling cascades. Most of the proteasome foci were detected between the condensed chromatin mass and inner nuclear membrane. The proteasome-positive puncta were not colocalized with other types of nuclear bodies and were reversibly dispersed when cells were returned to the isotonic medium. The structural integrity of 26S proteasomes in the nucleus was slightly affected under the hyperosmotic condition. We also found that these insulator-body-like proteasome foci were possibly formed through disrupted nucleus-to-cytosol transport, which was mediated by the sequestration of NPC components into osmostress-responding stress granules. These data suggest that phase separation in both the nucleus and cytosol may be a major cell survival mechanism during hyperosmotic stress conditions.

Marius W. Baeken, Mario Schwarz, Andreas Kern et al.

Abstract The sirtuin (SIRT) protein family has been of major research interest over the last decades because of their involvement in aging, cancer, and cell death. SIRTs have been implicated in gene and metabolic regulation through their capacity to remove acyl groups from lysine residues in proteins in an NAD+-dependent manner, which may alter individual protein properties as well as the histone–DNA interaction. Since SIRTs regulate a wide range of different signaling cascades, a fine-tuned homeostasis of these proteins is imperative to guarantee the function and survival of the cell. So far, however, how exactly this homeostasis is established has remained unknown. Here, we provide evidence that neuronal SIRT degradation in Parkinson’s disease (PD) models is executed by autophagy rather than the proteasome. In neuronal Lund human mesencephalic (LUHMES) cells, all seven SIRTs were substrates for autophagy and showed an accelerated autophagy-dependent degradation upon 1-methyl-4-phenylpyridinium (MPP+) mediated oxidative insults in vitro, whereas the proteasome did not contribute to the removal of oxidized SIRTs. Through blockade of endogenous H2O2 generation and supplementation with the selective radical scavenger phenothiazine (PHT), we could identify H2O2-derived species as the responsible SIRT-oxidizing agents. Analysis of all human SIRTs suggested a conserved regulatory motif based on cysteine oxidation, which may have triggered their degradation via autophagy. High amounts of H2O2, however, rapidly carbonylated selectively SIRT2, SIRT6, and SIRT7, which were found to accumulate carbonylation-prone amino acids. Our data may help in finding new strategies to maintain and modify SIRT bioavailability in neurodegenerative disorders.

I. A. Razumov, E. I. Kazachinskaya, L. I. Puchkova et al.

Toxicity and antiviral activity of aqueous extracts from higher mushrooms such as Lentinula edodes (Berk.) Pegler (shiitake), Pleurotus ostreatus (Jacq.) P. Kumm. (oyster), Inonotus obliquus (Ach. ex Pers.) Pilat (chaga), Hydnellum compactum (Pers.) P. Karst. (compact tooth) were studied. In doses of 0.8 to 4.0 mg (dry weight) per mouse administered orally or intraperitoneally the extracts showed no acute toxicity. When the dose of the chaga extract was increased to 20 mg per mouse, a half of the animals died. Intraperitoneal administration of the aqueous extracts in a dose of 0.4-2 mg per mouse prior to the contamination by a single LD50 of Herpes simplex type 2 provided 100-percent survival of the animals exposed to the Lentinula edodes or Pleurotus ostreatus extracts and 90-percent survival of the animals exposed to the Inonotus obliquus or Hydnellum compactum extracts.

Yue Jin, Zhangqian Liang, Huiqiang Lou

The forkhead box (Fox) transcription factors (TFs) are widespread from yeast to humans. Their mutations and dysregulation have been linked to a broad spectrum of malignant neoplasias. They are known as critical players in DNA repair, metabolism, cell cycle control, differentiation, and aging. Recent studies, especially those from the simple model eukaryotes, revealed unexpected contributions of Fox TFs in chromosome replication and organization. More importantly, besides functioning as a canonical TF in cell signaling cascades and gene expression, Fox TFs can directly participate in DNA replication and determine the global replication timing program in a transcription-independent mechanism. Yeast Fox TFs preferentially recruit the limiting replication factors to a subset of early origins on chromosome arms. Attributed to their dimerization capability and distinct DNA binding modes, Fkh1 and Fkh2 also promote the origin clustering and assemblage of replication elements (replication factories). They can mediate long-range intrachromosomal and interchromosomal interactions and thus regulate the four-dimensional chromosome organization. The novel aspects of Fox TFs reviewed here expand their roles in maintaining genome integrity and coordinating the multiple essential chromosome events. These will inevitably be translated to our knowledge and new treatment strategies of Fox TF-associated human diseases including cancer.

Werner Karl-Gustav Daalman, Els Sweep, Liedewij Laan

A bottom-up route towards predicting evolution relies on a deep understanding of the complex network that proteins form inside cells. In a rapidly expanding panorama of experimental possibilities, the most difficult question is how to conceptually approach the disentangling of such complex networks. These can exhibit varying degrees of hierarchy and modularity, which obfuscate certain protein functions that may prove pivotal for adaptation. Using the well-established polarity network in budding yeast as a case study, we first organize current literature to highlight protein entrenchments inside polarity. Following three examples, we see how alternating between experimental novelties and subsequent emerging design strategies can construct a layered understanding, potent enough to reveal evolutionary targets. We show that if you want to understand a cell’s evolutionary capacity, such as possible future evolutionary paths, seemingly unimportant proteins need to be mapped and studied. Finally, we generalize this research structure to be applicable to other systems of interest.

V S Veena, Preethi Sara George, K Rajan et al.

Context: Despite sputum cytology being accepted as a simple and noninvasive diagnostic method for lung cancer, the clinical usefulness of sputum for evaluation of prognosis is yet to be explored. Validation of some of the markers in sputum for prognosis prediction will be highly useful for selective therapy. Aims: This study was aimed to evaluate a reliable panel of immunocytochemical markers for their significance to predict survival. Materials and Methods: We have analyzed the expression of p53, p16, galectin-3, and epidermal growth factor receptor (EGFR) proteins in sputum samples processed in a mucolytic agent/cellblock and compared the same with that of the corresponding tissue samples. Results: Overexpression of p16 and EGFR was found to have a better survival benefit, whereas positive p53 and galectin-3 expressions had shorter period of survival. Expression patterns of all these four proteins were more or less similar in smears, cellblocks of sputum, and tissue samples except for slight changes in staining intensity which was not found to be statistically significant. No significant difference was found in the association of these proteins with survival pattern between sputum and tissue samples. Conclusion: This is the first report of immunocytochemistry of a panel of markers on cells exfoliated in sputum samples which suggests that analysis of immunocytochemical markers in sputum samples can be attempted as a cost-effective and reliable predictor of prognosis and survival. Accumulation of mutated p53, overexpression of galectin-3, and lower expression of p16 and EGFR proteins were found to predict poor prognosis for lung cancer.

Wen-Juan Wei, Bei Shi, Xin Guan et al.

Neural stem cells, which are capable of multi-potential differentiation and self-renewal, have recently been shown to have clinical potential for repairing central nervous system tissue damage. However, the theme trends and knowledge structures for human neural stem cells have not yet been studied bibliometrically. In this study, we retrieved 2742 articles from the PubMed database from 2013 to 2018 using “Neural Stem Cells” as the retrieval word. Co-word analysis was conducted to statistically quantify the characteristics and popular themes of human neural stem cell-related studies. Bibliographic data matrices were generated with the Bibliographic Item Co-Occurrence Matrix Builder. We identified 78 high-frequency Medical Subject Heading (MeSH) terms. A visual matrix was built with the repeated bisection method in gCLUTO software. A social network analysis network was generated with Ucinet 6.0 software and GraphPad Prism 5 software. The analyses demonstrated that in the 6-year period, hot topics were clustered into five categories. As suggested by the constructed strategic diagram, studies related to cytology and physiology were well-developed, whereas those related to neural stem cell applications, tissue engineering, metabolism and cell signaling, and neural stem cell pathology and virology remained immature. Neural stem cell therapy for stroke and Parkinson’s disease, the genetics of microRNAs and brain neoplasms, as well as neuroprotective agents, Zika virus, Notch receptor, neural crest and embryonic stem cells were identified as emerging hot spots. These undeveloped themes and popular topics are potential points of focus for new studies on human neural stem cells.

J. Bonenkamp, I. Songun, J. Hermans et al.

Aiko Amagai, Harry MacWilliams, Takahiro Isono et al.

We have previously demonstrated that a novel protein ZYG1 induces sexual cell fusion (zygote formation) of Dictyostelium cells. In the process of cell fusion, involvements of signal transduction pathways via Ca2+ and PKC (protein kinase C) have been suggested because zygote formation is greatly enhanced by PKC activators. In fact, there are several deduced sites phosphorylated by PKC in ZYG1 protein. Thereupon, we designed the present work to examine whether or not ZYG1 is actually phosphorylated by PKC and localized at the regions of cell-cell contacts where cell fusion occurs. These were ascertained, suggesting that ZYG1 might be the target protein for PKC. A humanized version of zyg1 cDNA (mzyg1) was introduced into myoblasts to know if ZYG1 is also effective in cell fusion of myoblasts. Quite interestingly, enforced expression of ZYG1 in myoblasts was found to induce markedly their cell fusion, thus strongly suggesting the existence of a common signaling pathway for cell fusion beyond the difference of species.

Matthias Buechter, Christian Georg Klein, Christian Kloeters et al.

A 68-year-old male patient was referred to our institution in May 2011 for a suspected tumor in the pancreatic head with consecutive jaundice. Using magnetic resonance imaging, further differentiation between chronic inflammation and a malignant process was not possible with certainty. Apart from cholestasis, laboratory studies showed increased values for CA 19-9 to 532 U/ml (normal <37 U/ml) and hypergammaglobulinemia (immunoglobulin G, IgG) of 19.3% (normal 8.0–15.8%) with an elevation of the IgG4 subtype to 2,350 mg/l (normal 52–1,250 mg/l). Endoscopic retrograde cholangiopancreatography revealed a prominent stenosis of the distal ductus hepaticus communis caused by pancreatic head swelling and also a bihilar stenosis of the main hepatic bile ducts. Cytology demonstrated inflammatory cells without evidence of malignancy. Under suspicion of autoimmune pancreatitis with IgG4-associated cholangitis, immunosuppressive therapy with steroids and azathioprine was started. Follow-up endoscopic retrograde cholangiopancreatography after 3 months displayed regressive development of the diverse stenoses. Jaundice had disappeared and blood values had returned to normal ranges. Moreover, no tumor of the pancreatic head was present in the magnetic resonance control images. Due to clinical and radiological similarities but a consecutive completely different prognosis and therapy, it is of fundamental importance to differentiate between pancreatic cancer and autoimmune pancreatitis. Especially, determination of serum IgG4 levels and associated bile duct lesions induced by inflammation should clarify the diagnosis of autoimmune pancreatitis and legitimate immunosuppressive therapy.

M. Sugiyama, Y. Atomi, N. Wada et al.

S. Lau, W. Wei, C. Hsu et al.