The Complement C3a and C5a Signaling in Renal Diseases: A Bridge between Acute and Chronic Inflammation.

The complement system, a cornerstone of the innate immune defense, typically confers protection against pathogens. However, in various clinical scenarios the complement's defensive actions can harm host cells, exacerbating immune and inflammatory responses. The central components C3 and C5 undergo proteolytic cleavage during complement activation, yielding small active fragments C3a and C5a anaphylatoxins.

A Geometric Feature-Based Algorithm for the Virtual Reading of Closed Historical Manuscripts.

X-ray Computed Tomography (CT), a commonly used technique in a wide variety of research fields, nowadays represents a unique and powerful procedure to discover, reveal and preserve a fundamental part of our patrimony: ancient handwritten documents. For modern and well-preserved ones, traditional document scanning systems are suitable for their correct digitization, and, consequently, for their preservation; however, the digitization of ancient, fragile and damaged manuscripts is still a formidable challenge for conservators. The X-ray tomographic approach has already proven its effectiveness in data acquisition, but the algorithmic steps from tomographic images to real page-by-page extraction and reading are still a difficult undertaking.

Sirt3 deficiency promotes endothelial dysfunction and aggravates renal injury.

Sirtuin 3 (SIRT3), the main deacetylase of mitochondria, modulates the acetylation levels of substrates governing metabolism and oxidative stress. In the kidney, we showed that SIRT3 affects the proper functioning of high energy-demanding cells, such as tubular cells and podocytes. Less is known about the role of SIRT3 in regulating endothelial cell function and its impact on the progression of kidney disease.

SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling.

The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect of the spike protein subunit 1 (S1) in inducing lung vascular damage and the potential mechanisms contributing to lung injury. Here, we found that S1 injection in mice transgenic for human angiotensin converting enzyme 2 (ACE2) induced early loss of lung endothelial thromboresistance at 3 days, as revealed by thrombomodulin loss and von Willebrand factor (vWF) increase.

Direct evidence that late Neanderthal occupation precedes a technological shift in southwestern Italy.

Objectives: During the middle-to-upper Paleolithic transition (50,000 and 40,000 years ago), interaction between Neanderthals and Homo sapiens varied across Europe. In southern Italy, the association between Homo sapiens fossils and non-Mousterian material culture, as well as the mode and tempo of Neanderthal demise, are still vividly debated. In this research, we focus on the study of two human teeth by using 3D geometric morphometric approaches for a reliable taxonomical attribution as well as obtaining new radiometric dates on the archeological sequence.

Low Nephron Number Induced by Maternal Protein Restriction Is Prevented by Nicotinamide Riboside Supplementation Depending on Sirtuin 3 Activation.

A reduced nephron number at birth, due to critical gestational conditions, including maternal malnutrition, is associated with the risk of developing hypertension and chronic kidney disease in adulthood. No interventions are currently available to augment nephron number. We have recently shown that sirtuin 3 (SIRT3) has an important role in dictating proper nephron endowment.

Shiga Toxin 2 Triggers C3a-Dependent Glomerular and Tubular Injury through Mitochondrial Dysfunction in Hemolytic Uremic Syndrome.

Shiga toxin (Stx)-producing is the predominant offending agent of post-diarrheal hemolytic uremic syndrome (HUS), a rare disorder of microvascular thrombosis and acute kidney injury possibly leading to long-term renal sequelae. We previously showed that C3a has a critical role in the development of glomerular damage in experimental HUS. Based on the evidence that activation of C3a/C3a receptor (C3aR) signaling induces mitochondrial dysregulation and cell injury, here we investigated whether C3a caused podocyte and tubular injury through induction of mitochondrial dysfunction in a mouse model of HUS.

X-ray Digital Radiography and Computed Tomography.

In recent years, X-ray imaging has rapidly grown and spread beyond the medical field; today, it plays a key role in diverse research areas [...

SARS-CoV-2 Spike Protein 1 Activates Microvascular Endothelial Cells and Complement System Leading to Platelet Aggregation.

Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 to infect and replicate in endothelial cells, it has been poorly investigated whether, in the complexity of viral infection in the human host, specific viral elements alone can induce endothelial damage. Detection of circulating spike protein in the sera of severe COVID-19 patients was evaluated by ELISA.

X-ray Tomography Unveils the Construction Technique of Un-Montu's Egyptian Coffin (Early 26th Dynasty).

The Bologna Archaeological Museum, in cooperation with prestigious Italian universities, institutions, and independent scholars, recently began a vast investigation programme on a group of Egyptian coffins of Theban provenance dating to the first millennium BC, primarily the 25th-26th Dynasty ( 746-525 BC). Herein, we present the results of the multidisciplinary investigation carried out on one of these coffins before its restoration intervention: the anthropoid wooden coffin of Un-Montu (Inv. MCABo EG1960).

Post-translational modifications by SIRT3 de-2-hydroxyisobutyrylase activity regulate glycolysis and enable nephrogenesis.

Abnormal kidney development leads to lower nephron number, predisposing to renal diseases in adulthood. In embryonic kidneys, nephron endowment is dictated by the availability of nephron progenitors, whose self-renewal and differentiation require a relatively repressed chromatin state. More recently, NAD-dependent deacetylase sirtuins (SIRTs) have emerged as possible regulators that link epigenetic processes to the metabolism.

Unique foot posture in Neanderthals reflects their body mass and high mechanical stress.

Neanderthal foot bone proportions and morphology are mostly indistinguishable from those of Homo sapiens, with the exception of several distinct Neanderthal features in the talus. The biomechanical implications of these distinct talar features remain contentious, fueling debate around the adaptive meaning of this distinctiveness. With the aim of clarifying this controversy, we test phylogenetic and behavioral factors as possible contributors, comparing tali of 10 Neanderthals and 81 H.

"Ecce Homo" by Antonello da Messina, from non-invasive investigations to data fusion and dissemination.

Scientific investigations of artworks are crucial in terms of preservation since they provide a measurable evaluation of the materials and the state of conservation. This is the case of Antonello da Messina's painting "Ecce Homo": its delicate state of conservation, with the need for constant monitoring, required a broad and in-depth diagnostic campaign to support the restorers. The project was carried out entirely in situ using non-invasive cutting-edge techniques and proposes a multimodal and data-centric approach, integrating 3D and 2D methodologies.

The ultimate database to (re)set the evolutionary history of primate genital bones.

Scientific literature concerning genital bones in primates consists of both ancient works (dating back to the nineteenth century) and more recent revisions/meta-analyses, which, however, are not always so detailed or exhaustive. Based on a thorough analysis, several conflicting data, inaccurate references, and questionable claims have emerged. We generated a binary matrix of genital bone occurrence data, considering only data at the species level, based on (1) a rigorous literature search protocol, (2) raw data (collected exclusively from primary literature), (3) an updated taxonomy (often tracing back to the species taxonomic history) and (4) new occurrence data from scanned genitals of fresh and museum specimens (using micro-computed tomography-micro-CT).

Unveiling an odd fate after death: The isolated Eneolithic cranium discovered in the Marcel Loubens Cave (Bologna, Northern Italy).

An isolated human cranium, dated to the early Eneolithic period, was discovered in 2015 at the top of a vertical shaft in the natural Marcel Loubens gypsum Cave (Bologna area, northern Italy). No other anthropological or archaeological remains were found inside the cave. In other caves of the same area anthropic and funerary use are attested from prehistory to more recent periods.

C3a receptor blockade protects podocytes from injury in diabetic nephropathy.

Renal activation of the complement system has been described in patients with diabetic nephropathy (DN), although its pathological relevance is still ill-defined. Here, we studied whether glomerular C3a, generated by uncontrolled complement activation, promotes podocyte damage, leading to proteinuria and renal injury in mice with type 2 diabetes. BTBR ob/ob mice exhibited podocyte loss, albuminuria, and glomerular injury accompanied by C3 deposits and increased C3a and C3a receptor (C3aR) levels.

A 3D journey on virtual surfaces and inner structure of ossa genitalia in Primates by means of a non-invasive imaging tool.

Novel bio-imaging techniques such as micro-Computed Tomography provide an opportunity to investigate animal anatomy and morphology by overcoming limitations imposed by traditional anatomical drawings. The primate genital bones are complex anatomical structures whose occurrence in both male penis (baculum) and female clitoris (baubellum) may be difficult to assess in individual cadavers. We tested a 3-step methodological protocol, including different techniques ranging from inexpensive/simple to more expensive/sophisticated ones, by applying it to a sample of primate species, and resulting in different levels of data complexity: (1) presence/absence manual palpation method; (2) 2D X-ray plates; 3) 3D micro-CT scans.

Protective Effects of Human Nonrenal and Renal Stromal Cells and Their Conditioned Media in a Rat Model of Chronic Kidney Disease.

Mesenchymal stromal cells (MSCs) are emerging as a novel therapeutic option for limiting chronic kidney disease progression. Conditioned medium (CM) containing bioactive compounds could convey similar benefits, avoiding the potential risks of cell therapy. This study compared the efficacy of nonrenal and renal cell-based therapy with the corresponding CM in rats with renal mass reduction (RMR).

Stem Cell Therapies in Kidney Diseases: Progress and Challenges.

The prevalence of renal diseases is emerging as a public health problem. Despite major progress in supportive therapy, mortality rates among patients remain high. In an attempt to find innovative treatments to stimulate kidney regeneration, stem cell-based technology has been proposed as a potentially promising strategy.

Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome.

Shiga toxin (Stx)-producing (STEC) infections have become a threat to public health globally because of the severe illnesses that they can trigger, such as hemorrhagic colitis and the post-diarrheal hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. Glomerular endothelial cells are primary targets of Stx which, after binding to its specific receptor globotriaosylceramide, upregulates proinflammatory proteins involved both in the recruitment and adhesion of leukocytes and thrombus formation at the site of endothelial injury. In this review, we discuss the role of complement activation in promoting glomerular microvascular dysfunction, providing evidence from experimental models and patients with STEC-HUS.

Production of Ga-68 with a General Electric PETtrace cyclotron by liquid target.

Purpose: In recent years the use of Ga (t = 67.84 min, β: 88.88%) for the labelling of different PET radiopharmaceuticals has significantly increased.

Therapeutic potential of stromal cells of non-renal or renal origin in experimental chronic kidney disease.

Background: Mesenchymal stromal cell (MSC)-based therapy is a promising strategy for preventing the progression of chronic kidney disease (CKD), with the potential to induce tissue regeneration. In search of the best cellular source we compared, in the rat model of adriamycin (ADR) nephropathy, the regenerative potential of human stromal cells of non-renal origin, such as bone marrow (bm) MSCs and umbilical cord (uc) MSCs, with that of newly discovered stromal cells of renal origin, the kidney perivascular cells (kPSCs) known to exhibit tissue-specific properties.

Methods: The therapeutic effect of repeated infusions of human bmMSCs, ucMSCs, kPSCs (1.

SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have pleiotropic properties beyond blood glucose-lowering effects and modify important nonglycemic pathways, leading to end-organ protection. SGLT2 inhibitors display renoprotective effects in diabetic kidney disease, which creates a rationale for testing the therapeutic potential of this drug class in nondiabetic chronic kidney disease. Here, we have shown that dapagliflozin provided glomerular protection in mice with protein-overload proteinuria induced by bovine serum albumin (BSA), to a similar extent as an ACE inhibitor used as standard therapy for comparison.

Sirtuins in Renal Health and Disease.

Sirtuins belong to an evolutionarily conserved family of NAD-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1-7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging.