ABSTRACT
With the advent of whole-slide imaging (WSI), a technology that can digitally scan whole slides in high resolution, pathology is undergoing a digital revolution. Detecting microsatellite instability (MSI) in colorectal cancer is crucial for proper treatment, as it identifies patients responsible for immunotherapy. Even though universal testing for MSI is recommended, particularly in patients affected by colorectal cancer (CRC), many patients remain untested, and they reside mainly in low-income countries. A critical need exists for accessible, low-cost tools to perform MSI pre-screening. Here, the potential predictive role of the most relevant artificial intelligence-driven models in predicting microsatellite instability directly from histology alone is discussed, focusing on CRC. The role of deep learning (DL) models in identifying the MSI status is here analyzed in the most relevant studies reporting the development of algorithms trained to this end. The most important performance and the most relevant deficiencies are discussed for every AI method. The models proposed for algorithm sharing among multiple research and clinical centers, including federal learning (FL) and swarm learning (SL), are reported. According to all the studies reported here, AI models are valuable tools for predicting MSI status on WSI alone in CRC. The use of digitized H&E-stained sections and a trained algorithm allow the extraction of relevant molecular information, such as MSI status, in a short time and at a low cost. The possible advantages related to introducing DL methods in routine surgical pathology are underlined here, and the acceleration of the digital transformation of pathology departments and services is recommended.
ABSTRACT
Atherosclerosis is a complex disease characterized by the accumulation of plaques in arterial walls. Understanding its pathogenesis remains incomplete, with factors like inflammation, oxidative stress, and hypertension playing critical roles. The disease exhibits preferential localization of plaques, with variability observed even within the same individual. Genetic, environmental, and lifestyle factors contribute to its heterogeneity. Histological plaque phenotypes vary widely, prompting classification schemes focusing on systemic and local factors deteriorating fibrous caps. Recent research highlights differences in plaque histology among arterial systems, suggesting unique pathophysiological mechanisms. This study reports on multiple atherosclerotic plaques detected at autopsy in various vascular sites of a single subject, emphasizing their histological diversity and underscoring the systemic nature of atherosclerosis.
ABSTRACT
The theory of fetal programming of adult diseases was first proposed by David J.P. Barker in the eighties of the previous century, to explain the higher susceptibility of some people toward the development of ischemic heart disease. According to his hypothesis, poor maternal living conditions during gestation represent an important risk factor for the onset of atherosclerotic heart disease later in life. The analysis of the early phases of fetal development is a fundamental tool for the risk stratification of children and adults, allowing the identification of susceptible or resistant subjects to multiple diseases later in life. Here, we provide a narrative summary of the most relevant evidence supporting the Barker hypothesis in multiple fields of medicine, including neuropsychiatric disorders, such as Parkinson disease and Alzheimer disease, kidney failure, atherosclerosis, coronary heart disease, stroke, diabetes, cancer onset and progression, metabolic syndrome, and infectious diseases including COVID-19. Given the consensus on the role of body weight at birth as a practical indicator of the fetal nutritional status during gestation, every subject with a low birth weight should be considered an "at risk" subject for the development of multiple diseases later in life. The hypothesis of the "physiological regenerative medicine," able to improve fetal organs' development in the perinatal period is discussed, in the light of recent experimental data indicating Thymosin Beta-4 as a powerful growth promoter when administered to pregnant mothers before birth.
ABSTRACT
BACKGROUND: Mucoepidermoid carcinoma of the breast is a rare special type of salivary gland-like tumor of the breast, usually displaying triple-negative phenotype. To date, only 64 cases have been reported in the English literature. Herein, we report the first case of mucoepidermoid carcinoma of the breast with human epidermal growth factor receptor 2 gene amplification. CASE PRESENTATION: A 58-year-old Caucasian woman treated with breast-conserving surgery, radiotherapy, and chemotherapy for an invasive breast carcinoma of no special type, relapsed 20 years later in the ipsilateral left breast. Histological examination of the core needle biopsy of the relapse deferred to the surgical specimen for the definitive diagnosis, because of the broad differential diagnosis. On the resected specimen we observed the presence of a poorly differentiated carcinoma with mucoepidermoid carcinoma of the breast typical features consisting of epidermoid, intermediate and mucinous cells lacking true keratinization, in keeping with the latest World Health Organization diagnostic criteria. The mucoepidermoid carcinoma of the breast was weakly estrogen receptor and androgen receptor positive and progesterone receptor negative, but exceptionally showed human epidermal growth factor receptor 2 gene amplification. Mastermind-like transcriptional coactivator 2 gene translocations were not detected by fluorescent in situ hybridization. The patient received adjuvant chemotherapy with anti-human epidermal growth factor receptor 2 therapy but no endocrine therapy. After 61 months of follow-up, no signs of local or distant recurrence were observed. CONCLUSIONS: Mucoepidermoid carcinoma of the breast is a very rare entity. Despite being most frequently triple negative, the standard evaluation of receptor status is mandatory, as well as strict application of World Health Organization diagnostic criteria for correct patient management.
Subject(s)
Breast Neoplasms , Carcinoma, Mucoepidermoid , Female , Humans , Middle Aged , Carcinoma, Mucoepidermoid/diagnosis , Carcinoma, Mucoepidermoid/genetics , Carcinoma, Mucoepidermoid/pathology , In Situ Hybridization, Fluorescence , Neoplasm Recurrence, Local/pathology , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Breast Neoplasms/diagnosis , Salivary Glands/pathologyABSTRACT
OBJECTIVES: The main objective of this retrospective, longitudinal, cohort study was to describe the occurrence of peri-zygomatic infection (PZI) as a complication associated with zygomatic implant (ZI) placement in a period of 22 years. MATERIALS AND METHODS: A retrospective search was carried out in the department of oral and maxillofacial surgery of Saint John's hospital in Genk, Belgium. Patients that had a severely atrophic fully or partially edentulous maxilla, and at least one ZI placed, were included. RESULTS: A total of 302 eligible patients, underwent ZI surgery between 1998 and 2020. From a total of 940 ZI, 45 were associated with the development of PZI. PZI was located in the upper portion of the cheek in relation to the external corner of the eye, one or two centimeters under the lower lid. The total number of affected patients was 25 (8.3%), who had a mean age of 58.1 years. In this subset, PZI occurred in 15 cases on the right side, in eight cases on the left side, and in two cases bilaterally. Ultimately, 16 ZI were lost in the PZI site. The mean time since the implant placement to the diagnosis of PZI was 1.9 years (SD ±2.4) and to the ZI removal of 3.8 years (SD ±3.7). After implant removal, the PZI symptomatology dissipated in all patients. CONCLUSION: Peri-zygomatic infection should be informed to the patients as a possible complication after ZI placement. Once identified, it should be acknowledged as a risk factor for ZI failure.
Subject(s)
Dental Implants , Jaw, Edentulous , Cohort Studies , Dental Implantation, Endosseous/adverse effects , Dental Implants/adverse effects , Dental Prosthesis, Implant-Supported , Follow-Up Studies , Humans , Jaw, Edentulous/surgery , Longitudinal Studies , Maxilla/surgery , Middle Aged , Retrospective Studies , Treatment Outcome , Zygoma/surgeryABSTRACT
Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.
Subject(s)
Liver/drug effects , Liver/injuries , Zinc/pharmacology , COVID-19/complications , Chelating Agents/metabolism , Copper/metabolism , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/drug therapy , Hepatolenticular Degeneration/metabolism , Humans , Liver/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , SARS-CoV-2/pathogenicity , Zinc/deficiency , Zinc/metabolism , COVID-19 Drug TreatmentABSTRACT
In recent years, the spectrum of possible applications of gold in diagnostics and therapeutic approaches in clinical practice has changed significantly, becoming surprisingly broad. Nowadays, gold-based therapeutic agents are used in the therapy of multiple human diseases, ranging from degenerative to infectious diseases and, in particular, to cancer. At the basis of these performances of gold, there is the development of new gold-based nanoparticles, characterized by a promising risk/benefit ratio that favors their introduction in clinical trials. Gold nanoparticles appear as attractive elements in nanomedicine, a branch of modern clinical medicine, which combines high selectivity in targeting tumor cells and low toxicity. Thanks to these peculiar characteristics, gold nanoparticles appear as the starting point for the development of new gold-based therapeutic strategies in oncology. Here, the new gold-based therapeutic agents developed in recent years are described, with particular emphasis on the possible applications in clinical practice as anticancer agents, with the aim that their application will give rise to a new golden age in oncology and a breakthrough in the fight against cancer.
ABSTRACT
Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers' residential BC exposure during pregnancy (0.63-2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.
Subject(s)
Air Pollutants/metabolism , Maternal Exposure/adverse effects , Maternal-Fetal Exchange , Placenta/metabolism , Soot/metabolism , Air Pollutants/toxicity , Belgium , Biopsy , Cohort Studies , Ecotoxicology , Female , Humans , Microscopy, Electron, Transmission , Permeability , Placenta/pathology , Placenta/ultrastructure , Pregnancy , Residence Characteristics/statistics & numerical data , Soot/analysis , Soot/toxicityABSTRACT
The study of neuropathological markers in patients affected by mental/psychiatric disorders is relevant for the comprehension of the pathogenesis and the correlation with the clinical symptomatology. The neuropathology of Alzheimer's disease (AD) recognizes intraneuronal and extracellular neurofibrillary formation responsible for neuronal degeneration. Immunohistochemical studies discovered many interesting results for a better interpretation of the AD pathogenesis, while the "metal hypothesis" supports that metal ions might differentially influence the formation of amyloid aggregates. The most relevant pathological findings reported in schizophrenia originate from computer assisted tomography (CT), Magnetic Resonance Imaging (MRI) studies and Diffusion Tensor Imaging (DTI), suggesting the brain abnormalities involved in the pathophysiology of schizophrenia. The theory of fetal programming illustrates the epigenetic factors that may act during the intrauterine life on brain development, with relevant consequences on the susceptibility to develop AD or schizophrenia later in life. The neuropathological interpretation of AD and schizophrenia shows that the presence of severe neuropathological changes is not always associated with severe cognitive impairment. A better dialogue between psychiatrics and pathologists might help to halt insurgence and progression of neurodegenerative diseases.
Subject(s)
Alzheimer Disease/pathology , Fetal Development , Schizophrenia/pathology , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Biomarkers , Brain/metabolism , Brain/pathology , Epigenesis, Genetic , Humans , Iron Overload/metabolism , Iron Overload/pathology , Schizophrenia/genetics , Schizophrenia/metabolismABSTRACT
OBJECTIVE: No therapy for non-alcoholic steatohepatitis (NASH) has been approved so far. Roux-en-y gastric bypass (RYGB) is emerging as a therapeutic option, although its effect on NASH and related hepatic molecular pathways is unclear from human studies. We studied the effect of RYGB on pre-existent NASH and hepatic mitochondrial dysfunction-a key player in NASH pathogenesis-in a novel diet-induced mouse model nicely mimicking human disease. DESIGN: C57BL/6J mice were fed a high-fat high-sucrose diet (HF-HSD). RESULTS: HF-HSD led to early obesity, insulin resistance and hypercholesterolaemia. HF-HSD consistently induced NASH (steatosis, hepatocyte ballooning and inflammation) with fibrosis already after 12-week feeding. NASH was accompanied by hepatic mitochondrial dysfunction, characterised by decreased mitochondrial respiratory chain (MRC) complex I and IV activity, ATP depletion, ultrastructural abnormalities, together with higher 4-hydroxynonenal (HNE) levels, increased uncoupling protein 2 (UCP2) and tumour necrosis factor-α (TNF-α) mRNA and free cholesterol accumulation. In our model of NASH and acquired mitochondrial dysfunction, RYGB induced sustained weight loss, improved insulin resistance and inhibited progression of NASH, with a marked reversal of fibrosis. In parallel, RYGB preserved hepatic MRC complex I activity, restored ATP levels, limited HNE production and decreased TNF-α mRNA. CONCLUSIONS: Progression of NASH and NASH-related hepatic mitochondrial dysfunction can be prevented by RYGB. RYGB preserves respiratory chain complex activity, thereby restoring energy output, probably by limiting the amount of oxidative stress and TNF-α. These data suggest that modulation of hepatic mitochondrial function contributes to the favourable effect of RYBG on established NASH.
Subject(s)
Gastric Bypass , Mitochondria, Liver/physiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/surgery , Animals , Humans , Insulin Resistance , Liver Diseases , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/physiopathology , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: The cytochrome P450 (CYP450) superfamily is implicated in important life processes, including metabolism of many molecules. CYP3A account for the largest portion of CYP450 proteins in human, including CYP3A4, CYP3A5 and CYP3A7. The purpose of this study was to investigate the immunohistochemical expression of CYP3A4 and CYP3A7 in human liver at different post-conceptional (PC) ages. METHODS: Human liver samples from 30 fetuses and newborns were, clustered according with the PC age, routinely processed for immunohistochemical analysis of CYP3A4 and CYP3A7. RESULTS: CYP3A4 was positive in all but two cases, CYP3A7 was positive in all but one case, which was negative also for CYP3A4. CONCLUSIONS: Our data on immunohistochemical detection of CYP3A4 and CYP3A7 during development show that CYP3A4 expression is not restricted to the post-natal age, being the immunostaining for both CYP3A4 and CYP3A7 identical after 25 weeks of PC age, thus the relationship between these CYP450 isoforms should be considered much more complex than previous thought. A high interindividual variability was observed among subjects at all gestational age. The variable CYP3A expression suggests the existence of a marked interindividual variability in drug metabolism during the intrauterine life and in perinatal period.
ABSTRACT
BACKGROUND: During the last years, human newborns have been overexposed to biologically reactive aluminum, with possible relevant consequences on their future health and on their susceptibility to a variety of diseases. Children, newborns and particularly preterm neonates are at an increased risk of aluminum toxicity because of their relative immaturity. DATA SOURCES: Based on recent original publications and classical data of the literatures, we reviewed the aluminum content in mother's food during the intrauterine life as well as in breast milk and infant formula during lactation. We also determined the possible role of aluminum in parenteral nutrition solutions, in adjuvants of vaccines and in pharmaceutical products. A special focus is placed on the relationship between aluminum overexposure and the insurgence of bone diseases. RESULTS: Practical points of management and prevention are suggested. Aluminum sources that infants may receive during the first 6 months of life are presented. In the context of prevention of possible adverse effects of aluminum overload in fetal tissues during development, simple suggestions to pregnant women are described. Finally, practical points of management and prevention are suggested. CONCLUSIONS: Pediatricians and neonatologists must be more concerned about aluminum content in all products our newborns are exposed to, starting from monitoring aluminum concentrations in milk- and soy-based formulas in which, on the basis of recent studies, there is still too much aluminum.
Subject(s)
Aluminum/analysis , Infant, Newborn , Adjuvants, Pharmaceutic/chemistry , Aluminum/toxicity , Animals , Female , Food, Formulated/analysis , Humans , Infant Formula/chemistry , Maternal-Fetal Exchange , Milk/chemistry , Milk, Human/chemistry , Parenteral Nutrition/adverse effects , Pharmaceutical Preparations/chemistry , PregnancyABSTRACT
In recent years, it has been clearly evidenced that most cells in a human being are not human: they are microbial, represented by more than 1000 microbial species. The vast majority of microbial species give rise to symbiotic host-bacterial interactions that are fundamental for human health. The complex of these microbial communities has been defined as microbiota or microbiome. These bacterial communities, forged over millennia of co-evolution with humans, are at the basis of a partnership with the developing human newborn, which is based on reciprocal molecular exchanges and cross-talking. Recent data on the role of the human microbiota in newborns and children clearly indicate that microbes have a potential importance to pediatrics, contributing to host nutrition, developmental regulation of intestinal angiogenesis, protection from pathogens, and development of the immune system. This review is aimed at reporting the most recent data on the knowledge of microbiota origin and development in the human newborn, and on the multiple factors influencing development and maturation of our microbiota, including the use and abuse of antibiotic therapies.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbiota/drug effects , Microbiota/physiology , Biological Evolution , Child Development/physiology , Gastrointestinal Tract/drug effects , Gastrointestinal Tract/immunology , Gastrointestinal Tract/microbiology , Humans , Individuality , Infant, Newborn , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Parturition/physiologyABSTRACT
CD44 is a transmembrane adhesion glycoprotein, functioning as a hyaluronan receptor and participating in the uptake and degradation of hyaluronan. Recently, CD44 has been proposed in the adult kidney as a marker of activated glomerular parietal epithelial cells, the putative niche stem cells that, in case of damage to podocytes, might migrate inside the glomerular tuft and undergo transition to podocytes. Here, immunoreactivity for CD44 was tested in 18 human fetuses and newborns with a gestational age ranging from 11 to 39 weeks. CD44 immunoreactivity was observed in all but one developing kidneys, being localized in several renal cell types including intraglomerular, capsular, cortical and medullary interstitial cells and nerve cells. In some cases, CD44 marked scattered cells in nephrogenic subcapsular zone. Our data indicate that CD44 is involved in human nephrogenesis, probably marking a subset of progenitor/stem cells involved in early phases of kidney development and, putatively, in podocyte and/or interstitial cell differentiation.
Subject(s)
Hyaluronan Receptors/metabolism , Hyaluronic Acid/metabolism , Kidney , Podocytes , Stem Cells/physiology , Biomarkers/metabolism , Cell Differentiation/physiology , Cell Transdifferentiation/physiology , Female , Fetus , Gestational Age , Humans , Immunohistochemistry , Infant, Newborn , Kidney/embryology , Kidney/growth & development , Kidney/pathology , Male , Organogenesis , Podocytes/immunology , Podocytes/metabolismABSTRACT
An emerging hypothesis from the recent literature explain how specific adverse factors related with growth retardation as well as of low birth weight (LBW) might influence renal development during fetal life and then the insurgence of hypertension and renal disease in adulthood. In this article, after introducing a brief overview of human nephrogenesis, the most important factors influencing nephron number at birth will be reviewed, focusing on the "in utero" experiences that lead to an increased risk of developing hypertension and/or kidney disease in adult. Since nephrogenesis in preterm human newborns does not stop at birth, but it continues for 4-6 weeks postnatally, a better knowledge of the mechanisms able to accelerate nephrogenesis in the perinatal period, could represent a powerful tool in the hands of neonatologists. We suggest to define this approach to a possible therapy of a deficient nephrogenesis at birth "physiological renal regenerating medicine". Our goal in preterm infants, especially VLBW, could be to prolong the nephrogenesis not only for 6 weeks after birth but until 36 weeks of post conceptual age, allowing newborn kidneys to restore their nephron endowment, escaping susceptibility to hypertension and to renal disease later in life.
Subject(s)
Kidney Diseases/embryology , Nephrons/embryology , Animals , Humans , Infant, Newborn , Infant, Very Low Birth Weight , Kidney Diseases/prevention & control , Nephrons/growth & development , Nephrons/ultrastructureABSTRACT
The result of the use of drugs in the newborn may be strongly influenced by the peculiar state of the neonate, characterized by the immaturity, at birth, of the processes controlling the absorption, distribution, metabolism and excretion of drugs. Additional important factors that may affect drugs' bioavailability and toxicity are gestational age, birth weight, intrauterine growth restriction, gender and, especially, liver function immaturity. Because of the high susceptibility to infections, antibiotics, in particular ampicillin and gentamicin, are the most widely used drugs in newborns. Erythromycin is often used for the therapy of gastrointestinal dismotility, while azithromycin has been proposed for the prevention of bronchopulmonary dysplasia. Prostaglandin synthesis inhibitors, like indomethacin, are administered on the first days of life to close the patent ductus arteriosus. All these drugs have been proved to can give rise to hepatotoxicity. The acute and chronic liver toxicity due to the most widely used drugs in the neonates will be here reviewed.
Subject(s)
Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Anti-Bacterial Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Chemical and Drug Induced Liver Injury/classification , Liver/metabolism , Acetaminophen/metabolism , Age Factors , Analgesics, Non-Narcotic/metabolism , Anti-Bacterial Agents/metabolism , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Humans , Infant, NewbornABSTRACT
Bronchogenic cysts are mostly benign, congenital abnormalities originating from the remnants of the primitive foregut. A retroperitoneal location is rare. Due to the mostly asymptomatic behavior and the historical confusion regarding histology, an exact prevalence is not known. We present here a case report of a retroperitoneal bronchogenic cyst. A literature review was performed for cases of retroperitoneal bronchogenic cysts written in English. Anatomopathological criteria for inclusion were pseudo stratified, ciliated, columnar epithelium together with the presence of at least one of the following: cartilage, smooth muscle or seromucous glands. In addition, the embryology, pathogenesis, radiological, clinical and suggested treatment modalities are reviewed. We report the surgical excision of a retroperitoneal bronchogenic cyst that presented as a non-functioning left adrenal mass. Our review of literature revealed only 62 potential cases of retroperitoneal bronchogenic cysts. After applying the strict anatomopathological criteria, only 30 cases of true retroperitoneal bronchogenic cysts could be identified. Retroperitoneal location of a bronchogenic cyst is rare. Despite the rarity of this pathologic entity, bronchogenic cysts should be considered in the differential diagnosis of retroperitoneal cystic lesions. Only histology can confirm definitive diagnosis. Surgery remains the recommended treatment of choice.
ABSTRACT
The development of the human kidney is a complex process that requires interactions between epithelial and mesenchymal cells, eventually leading to the coordinated growth and differentiation of multiple highly specialized stromal, vascular, and epithelial cell types. The application of molecular biology and immunocytochemistry to the study of cell types involved in renal morphogenesis is leading to a better understanding of nephrogenesis, which requires a fine balance of many factors that can be disturbed by various prenatal events in humans. The aim of this paper is to review human kidney organogenesis, with particular emphasis on the sequence of morphological events, on the immunohistochemical peculiarities of nephron progenitor populations and on the molecular pathways regulating the process of mesenchymal to epithelial transition. Kidney development can be subdivided into five steps: (i) the primary ureteric bud (UB); (ii) the cap mesenchyme; (iii) the mesenchymal-epithelial transition; (iv) glomerulogenesis and tubulogenesis; (v) the interstitial cells. Complex correlations between morphological and molecular events from the origin of the UB and its branching to the metanephric mesenchyme, ending with the maturation of nephrons, have been reported in different animals, including mammals. Marked differences, observed among different species in the origin and the duration of nephrogenesis, suggest that morphological and molecular events may be different in different animal species and mammals. Further studies must be carried out in humans to verify at the morphological, immunohistochemical, and molecular levels if the outcome in humans parallels that previously described in other species.
Subject(s)
Gene Expression Regulation, Developmental/physiology , Kidney Diseases/embryology , Kidney Diseases/metabolism , Kidney/abnormalities , Kidney/embryology , Morphogenesis/physiology , Humans , Kidney Diseases/pathology , Morphogenesis/geneticsABSTRACT
Wilms Tumor 1 (WT1) is a zinc finger protein, expressed by human podocytes in the adult kidney, which plays a relevant role in different phases of nephrogenesis in experimental animals. Since no data are available for specific role in the human fetal kidney, this study aimed at investigating the expression of WT1 during the different phases of nephrogenesis. To this end, the expression of WT1 was evaluated in the kidneys, from four human fetuses and two newborns. WT1 immunoreactivity was detected in all the examined kidneys, but not in the kidneys of the newborn at term. Immunostaining for WT1 was observed in podocytes of the glomeruli and in the subcapsular regions, in areas of active glomerulogenesis. The extent and the intensity of immunoreactivity for WT1 changed from one case to the next according to the different gestational age. This study confirms in human kidney the relevant role played by WT1 during nephrogenesis. Its expression pattern suggests a main role in the regulation of the process of Mesenchimal-Epithelial-Transition and in the development and maturation of podocytes. Further studies are needed to verify the correlation between the expression pattern of WT1 and that of other genes products involved in nephrogenesis, in order to better understand their relationship at protein level.
Subject(s)
Kidney/embryology , Kidney/metabolism , WT1 Proteins/metabolism , Epithelial-Mesenchymal Transition/physiology , Female , Fetus/metabolism , Gene Expression Regulation, Developmental , Gestational Age , Humans , Immunohistochemistry , Infant, Newborn , Kidney/pathology , Male , Organogenesis/physiology , Podocytes/metabolism , Podocytes/pathologyABSTRACT
BACKGROUND: The development of the human kidney is a complex process requiring interactions between epithelial and mesenchymal cells. The condensed cap mesenchyme is hypothesized to generate a population of stem/progenitor cells that undergo mesenchymal-epithelial transition (MET) originating nephrons. Few immunohistochemical markers are available for detecting cap mesenchymal cells in the early phases of MET. METHODS: The expression of MUC1 was evaluated in the kidneys, of 4 human foetuses and 2 newborns. RESULTS: MUC1 immunoreactivity was detected in all the examined kidneys in the cap mesenchyme and in the renal vesicles. Immunostaining for MUC1 in cap mesenchymal cells changed from one nodule to the next: some mesenchymal nodules were negative, some showed MUC1 reactivity in scattered cells, whereas in others, positive cells revealed the presence of a roundish developing epithelial structure. CONCLUSIONS: Our data clearly indicates, for the first time to the best of our knowledge, immunohistochemical evidence of MUC1 expression during human kidney development. We focused on MUC1 reactivity in the cap mesenchyme. On the basis of these preliminary data, we speculate that MUC1 may be involved in human nephrogenesis and may play a relevant role in MET from the cap mesenchyme to the renal vesicle, changing the fate of renal stem/progenitor cells.