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Cancers May 2024The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal... (Review)
Review
The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called "other oncocytic tumors", namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.
PubMed: 38791935
DOI: 10.3390/cancers16101856 -
International Journal of Molecular... May 2024Mitochondrial protein homeostasis is crucially regulated by protein degradation processes involving both mitochondrial proteases and cytosolic autophagy. However, it...
Mitochondrial protein homeostasis is crucially regulated by protein degradation processes involving both mitochondrial proteases and cytosolic autophagy. However, it remains unclear how plant cells regulate autophagy in the scenario of lacking a major mitochondrial Lon1 protease. In this study, we observed a notable downregulation of core autophagy proteins in Lon1 knockout mutant and , supporting the alterations in the relative proportions of mitochondrial and vacuolar proteins over total proteins in the plant cells. To delve deeper into understanding the roles of the mitochondrial protease Lon1 and autophagy in maintaining mitochondrial protein homeostasis and plant development, we generated the double mutant by incorporating the loss-of-function mutation of the autophagy core protein ATG5, known as . The double mutant exhibited a blend of phenotypes, characterized by short plants and early senescence, mirroring those observed in the individual single mutants. Accordingly, distinct transcriptome alterations were evident in each of the single mutants, while the double mutant displayed a unique amalgamation of transcriptional responses. Heightened severity, particularly evident in reduced seed numbers and abnormal embryo development, was observed in the double mutant. Notably, aberrations in protein storage vacuoles (PSVs) and oil bodies were evident in the single and double mutants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of genes concurrently downregulated in , , and unveiled a significant suppression of genes associated with brassinosteroid (BR) biosynthesis and homeostasis. This downregulation likely contributes to the observed abnormalities in seed and embryo development in the mutants.
Topics: Arabidopsis; Arabidopsis Proteins; Autophagy; Seeds; Mitochondria; Gene Expression Regulation, Plant; Brassinosteroids; ATP-Dependent Proteases; Mutation; Mitochondrial Proteins; Down-Regulation; Phenotype; Serine Endopeptidases
PubMed: 38791463
DOI: 10.3390/ijms25105425 -
Foods (Basel, Switzerland) May 2024The antimicrobial function of citral, one of the main compounds of the essential oils (EO) of the genus, and widely used by the food industry toward spoilage yeast, was...
The antimicrobial function of citral, one of the main compounds of the essential oils (EO) of the genus, and widely used by the food industry toward spoilage yeast, was previously proven. In this study, the possible mode of action of citral against yeast cells was evaluated by using a global deletome approach. Firstly, the suitability of Σ1278b to serve as model yeast was assessed by determining its sensitivity to citral (MIC = 0.5 μL/mL). Subsequently, the complete library of Σ1278b haploid mutants deleted in 4019 non-essential genes was screened to identify potential molecular targets of citral. Finally, the deleted genes in the 590 mutants showing increased citral resistance was analyzed with an in-silico approach (Gene Ontology). The significantly enriched GO Terms were "cytoplasm", "vacuole", and "mitochondrion" (cellular components); "catalytic activity" (molecular function); "pseudohyphal growth" (biological process). For molecular function, resistant mutants were grouped into thiosulfate sulfur transferase activity, transferase activity, and oxidoreductase activity; for cellular components, resistant mutants were grouped as: cytoplasm, intracellular organelle, membrane-bounded organelle, mitochondrion, organelle membrane, and vacuole; and finally, with regard to biological process, deleted genes were grouped as: pseudohyphal growth, mitochondrion organization, lipid metabolic process, DNA recombination and repair, and proteolysis. Interestingly, many identified genes were associated with the cellular response to oxidative stress and ROS scavenging. These findings have important implications for the development of citral-based antimicrobials and the elucidation of its mechanism of action.
PubMed: 38790757
DOI: 10.3390/foods13101457 -
Ecotoxicology and Environmental Safety Jul 2024Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains...
BACKGROUND
Despite the known reproductive toxicity induced by triptolide (TP) exposure, the regulatory mechanism underlying testicular vacuolization injury caused by TP remains largely obscure.
METHODS
Male mice were subjected to TP at doses of 15, 30, and 60 μg/kg for 35 consecutive days. Primary Sertoli cells were isolated from 20-day-old rat testes and exposed to TP at concentrations of 0, 40, 80, 160, 320, and 640 nM. A Biotin tracer assay was conducted to assess the integrity of the blood-testis barrier (BTB). Transepithelial electrical resistance (TER) assays were employed to investigate BTB function in primary Sertoli cells. Histological structures of the testes and epididymides were stained with hematoxylin and eosin (H&E). The expression and localization of relevant proteins or pathways were assessed through Western blotting or immunofluorescence staining.
RESULTS
TP exposure led to dose-dependent testicular injuries, characterized by a decreased organ coefficient, reduced sperm concentration, and the formation of vacuolization damage. Furthermore, TP exposure disrupted BTB integrity by reducing the expression levels of tight junction (TJ) proteins in the testes without affecting basal ectoplasmic specialization (basal ES) proteins. Through the TER assay, we identified that a TP concentration of 160 nM was optimal for elucidating BTB function in primary Sertoli cells, correlating with reductions in TJ protein expression. Moreover, TP exposure induced changes in the distribution of the BTB and cytoskeleton-associated proteins in primary Sertoli cells. By activating the AKT/mTOR signaling pathway, TP exposure disturbed the balance between mTORC1 and mTORC2, ultimately compromising BTB integrity in Sertoli cells.
CONCLUSION
This investigation sheds light on the impacts of TP exposure on testes, elucidating the mechanism by which TP exposure leads to testicular vacuolization injury and offering valuable insights into comprehending the toxic effects of TP exposure on testes.
Topics: Male; Animals; Sertoli Cells; Diterpenes; Phenanthrenes; TOR Serine-Threonine Kinases; Signal Transduction; Testis; Epoxy Compounds; Proto-Oncogene Proteins c-akt; Mice; Blood-Testis Barrier; Cytoskeleton; Rats; Vacuoles; Rats, Sprague-Dawley
PubMed: 38788563
DOI: 10.1016/j.ecoenv.2024.116502 -
Pathogens (Basel, Switzerland) May 2024is an obligate intracellular Gram-negative bacterium that causes Q fever, a life-threatening zoonotic disease. replicates within an acidified parasitophorous vacuole...
is an obligate intracellular Gram-negative bacterium that causes Q fever, a life-threatening zoonotic disease. replicates within an acidified parasitophorous vacuole derived from the host lysosome. The ability of to replicate and achieve successful intracellular life in the cell cytosol is vastly dependent on the Dot/Icm type 4B secretion system (T4SSB). Although several T4SSB effector proteins have been shown to be important for virulence and intracellular replication, the role of the icmE protein in the host- interaction has not been investigated. In this study, we generated a Nine Mile Phase II (NMII) mutant library and identified 146 transposon mutants with a single transposon insertion. Transposon mutagenesis screening revealed that disruption of gene resulted in the attenuation of NMII virulence in SCID mice. ELISA analysis indicated that the levels of pro-inflammatory cytokines, including interleukin-1β, IFN-γ, TNF-α, and IL-12p70, in serum from Tn::icmE mutant-infected SCID mice were significantly lower than those in serum from wild-type (WT) NMII-infected mice. Additionally, Tn::icmE mutant bacteria were unable to replicate in mouse bone marrow-derived macrophages (MBMDM) and human macrophage-like cells (THP-1). Immunoblotting results showed that the Tn::icmE mutant failed to activate inflammasome components such as IL-1β, caspase 1, and gasdermin-D in THP-1 macrophages. Collectively, these results suggest that the icmE protein may play a vital role in virulence, intracellular replication, and activation of inflammasome mediators during NMII infection.
PubMed: 38787259
DOI: 10.3390/pathogens13050405 -
Pathogens (Basel, Switzerland) Apr 2024Human amoebiasis still represents a major health problem worldwide. Metronidazole has been used as the most common drug to treat the disease; however, it is also known...
Human amoebiasis still represents a major health problem worldwide. Metronidazole has been used as the most common drug to treat the disease; however, it is also known that the drug causes undesirable side effects. This has led to the search for new pharmacological alternatives which include phytochemical compounds with antiamoebic effects. We analyzed the amoebicidal activity of stevioside (STV), a diterpene glycoside present in , on trophozoites of . Different concentrations of STV were tested, and an inhibitory concentration of 50% of cell viability (IC) was determined with an exposition of 9.53 mM for 24 h. Trophozoites exposed to STV showed morphological changes evidenced by the decrease in the basic structures related to the movement and adherence to the substrate, as well as ultrastructural features characterized by a loss of regularity on the cell membrane, an increase in cytoplasmic granularity, and an increase in apparent autophagic vacuoles. Also, the decrease in cysteine protease expression and the proteolytic activity of trophozoites to degrade the cell monolayer were analyzed. A histological analysis of hamster livers inoculated with trophozoites and treated with STV showed changes related to the granulomatous reaction of the liver parenchymal tissue. Our results constitute the first report related to the possible use of STV as a therapeutic alternative in amoebiasis.
PubMed: 38787225
DOI: 10.3390/pathogens13050373 -
Biology Apr 2024Europium is one of the most reactive lanthanides and humans use it in many different applications, but we still know little about its potential toxicity and cellular...
Europium is one of the most reactive lanthanides and humans use it in many different applications, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model were adapted to high concentrations of two Eu(III) compounds (EuCl or EuO) and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl is more toxic than EuO. LC values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by EuO is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothioneins and/or displace essential cations of these proteins during their homeostatic function. Both lipid metabolism (lipid droplets fusing with europium-containing vacuoles) and autophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.
PubMed: 38785768
DOI: 10.3390/biology13050285 -
BMC Veterinary Research May 2024Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common...
BACKGROUND
Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood.
CASE PRESENTATION
We report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis.
CONCLUSIONS
In both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases.
Topics: Animals; Callithrix; Pneumatosis Cystoides Intestinalis; Emphysema; Male; Monkey Diseases; Stomach Diseases; Female; Duodenal Diseases
PubMed: 38783305
DOI: 10.1186/s12917-024-04087-8 -
Journal of Cytology 2024Atypical glandular cells (AGCs) diagnosis on Pap (Papanicolaou) smears are uncommon and may represent various benign and malignant lesions.
BACKGROUND
Atypical glandular cells (AGCs) diagnosis on Pap (Papanicolaou) smears are uncommon and may represent various benign and malignant lesions.
OBJECTIVE
This study aims to report the incidence of AGC on Pap smear, to study the relationship of AGC with malignancy, and to determine cytomorphological features that help in predicting malignancy.
MATERIALS AND METHODS
Retrospective analytical study conducted in the Department of Oncopathology at Tertiary Cancer and Research Institute. In this retrospective study, we included cases diagnosed with AGC between July 2017 to July 2022. All slides were reviewed and subclassified according to the Bethesda 2014 classification system (TBS). The predetermined cytomorphological features observed in the smears were recorded. The follow-up histopathological diagnoses of the cases were retrieved. The significant cytomorphological and clinicopathological findings for malignancy were determined.
RESULTS
Pearson χ test with SPSS software version 22 to compare cytologic features of cases with benign and malignant follow-up. The significant cytomorphological features observed in neoplastic cases were cells in 3-dimensional clusters, nuclear overlapping, reniform nucleus, irregular nuclear membrane, increased nuclear size, single macronucleoli, engulfed neutrophils, and prominently vacuolated cytoplasm.
CONCLUSIONS
The diagnosis of AGC on cytology is associated with clinically significant lesions, and cytomorphologic parameters can be used to predict the benign and malignant outcome.
PubMed: 38779602
DOI: 10.4103/joc.joc_172_23 -
BMC Veterinary Research May 2024The study aimed to assess the effects of water salinity on the sperm parameters, levels of cortisol, LH, FSH, testosterone and antioxidants as well as the testes'...
The study aimed to assess the effects of water salinity on the sperm parameters, levels of cortisol, LH, FSH, testosterone and antioxidants as well as the testes' histopathology in Barki rams. Fifteen healthy Barki rams (1-1.5 years) were divided into three equal depending on the type of drinking water for nine months. The rams in the tap water group (TW, water that contained 350 ppm of total dissolved salts (TDS). Males in the high saline water group (HSW) were permitted to consume high saline water with 8,934 ppm TDS, whereas those in the second group were permitted to have moderately saline water (MSW, 4,557 ppm TDS). High salt concentration in drinking water had adverse effect on sperm viability, morphology and sperm cell concertation. Nitric oxide and malondialdehyde concentrations in blood were significantly higher in the MSW and HSW groups than in TW. There was a significant decrease in glutathione concentration as well as superoxide dismutase activity in TDS and HSW. Cortisol was most highly concentrated in the HSW, next in the MSW, and least in TW. The testosterone, LH, and FSH concentrations in the HSW and MSW groups were significantly lower than in TW. As the salt concentration in drinking water increases, damage to testicular tissue. The MSW group demonstrating vacuolation of lining epithelial cells with pyknotic nuclei in the epididymis and necrosis and desquamation of spermatogenic cells in seminiferous tubules while HSW group displaying desquamated necrotic cells and giant cell formation in the epididymis, as well as damage to some of the seminiferous tubules and showed congestion, vacuolation of spermatogenic epithelium of seminiferous tubules, and desquamated necrotic spermatogenic epithelium. In conclusion, the salinity of the water has detrimental impacts on the sperm morphology, viability and concentration, hormones and antioxidant levels in Barki rams.
Topics: Male; Animals; Testis; Antioxidants; Spermatozoa; Sheep; Testosterone; Follicle Stimulating Hormone; Hydrocortisone; Saline Waters; Luteinizing Hormone
PubMed: 38778406
DOI: 10.1186/s12917-024-04047-2