Mononuclear Phagocytes, Cellular Immunity, and Nobel Prizes: A Historic Perspective.

The mononuclear phagocyte system includes monocytes, macrophages, some dendritic cells, and multinuclear giant cells. These cell populations display marked heterogeneity depending on their differentiation from embryonic and bone marrow hematopoietic progenitors, tissue location, and activation. They contribute to tissue homeostasis by interacting with local and systemic immune and non-immune cells through trophic, clearance, and cytocidal functions.

Spatial control of the APC/C ensures the rapid degradation of cyclin B1.

The proper control of mitosis depends on the ubiquitin-mediated degradation of the right mitotic regulator at the right time. This is effected by the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The SAC prevents the APC/C from recognising Cyclin B1, the essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to the spindle.

Drug repurposing screen identifies novel anti-inflammatory activity of sunitinib in macrophages.

Inflammation is a driver of human disease and an unmet clinical need exists for new anti-inflammatory medicines. As a key cell type in both acute and chronic inflammatory pathologies, macrophages are an appealing therapeutic target for anti-inflammatory medicines. Drug repurposing - the use of existing medicines for novel indications - is an attractive strategy for the identification of new anti-inflammatory medicines with reduced development costs and lower failure rates than de novo drug discovery.

CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer.

Background: Promoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated.

Results: In this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines.

Indirect signs of infravesical obstruction on voiding cystourethrography improve post-neonatal posterior urethral valves detection rate.

Objectives: To identify the diagnostic performance of clinical and radiological signs (on voiding cystourethrography [VCUG]) to detect posterior urethral valves (PUV) in the post-neonatal period.

Materials And Methods: One hundred eighteen males (median age = 0.8 years, range = 1 month-14 years, 48 toilet-trained) undergoing VCUG in a 2-year period were prospectively enrolled.

Nicotinamide N-methyltransferase (NNMT) regulates the glucocorticoid signaling pathway during the early phase of adipogenesis.

Obesity is associated with adipose tissue dysfunction through the differentiation and expansion of pre-adipocytes to adipocytes (hyperplasia) and/or increases in size of pre-existing adipocytes (hypertrophy). A cascade of transcriptional events coordinates the differentiation of pre-adipocytes into fully differentiated adipocytes; the process of adipogenesis. Although nicotinamide N-methyltransferase (NNMT) has been associated with obesity, how NNMT is regulated during adipogenesis, and the underlying regulatory mechanisms, remain undefined.

Early-in-Life Serum Aldosterone Levels Could Predict Surgery in Patients with Obstructive Congenital Anomalies of the Kidney and Urinary Tract: A Pilot Study.

The aim of the study was to evaluate whether serum aldosterone levels or plasmatic renin activity (PRA) measured early in life (1-3 months) could predict a future surgical intervention for obstructive congenital anomalies of kidney and urinary tract (CAKUT). Twenty babies aged 1-3 months of life with suspected obstructive CAKUT were prospectively enrolled. The patients underwent a 2-year follow-up and were classified as patients needing or not needing surgery.

Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities.

Drug repurposing is an attractive, pragmatic approach to drug discovery that has yielded success across medical fields over the years. The use of existing medicines for novel indications enables dramatically reduced development costs and timescales compared with drug discovery and is therefore a promising strategy in cardiovascular disease, where new drug approvals lag significantly behind that of other fields. Extensive evidence from pre-clinical and clinical studies show that chronic inflammation is a driver of pathology in cardiovascular disease, and many efforts have been made to target cardiovascular inflammation therapeutically.

Enhanced Detection of Viral RNA Species Using FokI-Assisted Digestion of DNA Duplexes and DNA/RNA Hybrids.

The accurate detection of nucleic acids from certain biological pathogens is critical for the diagnosis of human diseases. However, amplified detection of RNA molecules from a complex sample by direct detection of RNA/DNA hybrids remains a challenge. Here, we show that type IIS endonuclease FokI is able to digest DNA duplexes and DNA/RNA hybrids when assisted by a dumbbell-like fluorescent sensing oligonucleotide.

NF-κB Signaling and Inflammation-Drug Repurposing to Treat Inflammatory Disorders?

NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS).

Laparoscopic Trachelectomy for Cervix Yolk Sac Tumor in 11-Month-Old Girl: The Youngest Case.

Background: Yolk sac tumor (YST) is a malignant entity that often occurs in girls less than 3 years of age and is the most frequent type of primary extragonadal germ cell tumor.

Case: We describe the case of an 11-month-old girl who was referred to our center for vaginal bleeding with evidence of a uterine mass on ultrasonography. Preoperative investigations confirmed YST of the uterine cervix without metastasis.

Nicotinamide N-methyltransferase: At the crossroads between cellular metabolism and epigenetic regulation.

Background: The abundance of energy metabolites is intimately interconnected with the activity of chromatin-modifying enzymes in order to guarantee the finely tuned modulation of gene expression in response to cellular energetic status. Metabolism-induced epigenetic gene regulation is a key molecular axis for the maintenance of cellular homeostasis, and its deregulation is associated with several pathological conditions. Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that catalyzes the methylation of nicotinamide (NAM) using the universal methyl donor S-adenosyl methionine (SAM), directly linking one-carbon metabolism with a cell's methylation balance and nicotinamide adenine dinucleotide (NAD) levels.

Prognostic significance of the sum of the diameters of single foci in multifocal papillary thyroid cancer: the concept of new-old tumor burden.

Aim: The prognostic value of multifocality (Mu) in papillary thyroid cancer (PTC) remains controversial. The present study aimed to investigate this issue and test the possible prognostic significance of the sum of the diameters of single foci (SDSF), the total number of foci (TNF), and primary tumor size (PTS) in multifocal PTC.

Methods: We retrospectively analyzed a single-center consecutive series of 370 PTCs.

An investigation of spitefulness in violent offenders: Associations with the dark triad and emotion dysregulation.

Background: Spitefulness is the inclination to inflict harm to someone else even at one's own expenses. The development of a self-report measure (the Spitefulness Scale [SS]) has fostered the investigation of the relationships between spitefulness and aggression-related variables.

Objective: The present study aims to investigate the construct of spitefulness in violent offenders.

Individualized robotic organ-sparing surgery in a paediatric case of renal perivascular epithelioid cell tumour.

Background: Perivascular epithelioid cell tumours (PEComas) represent a rare group of mesenchymal tumours with an unpredictable outcome. They are usually observed in middle-aged women whilst they are very rare in children, with limited cases described. Due to the rare anatomical location in kidneys, a correct diagnosis and treatment is really challenging.

Posterior Urethral Polyp Treated With Endoscopic Transurethral Resection: The Second Pediatric Case Managed With Holmium Laser.

Fibroepithelial urethral polyp is a rare benign tumor more common in children than adult that can cause bladder outlet obstruction. We describe a 3-year-old boy who presented with intermittent acute urinary retention affected by a fibroepithelial urethral polyp managed with endoscopic transurethral resection by HOLMIUM laser; no complications neither recurrence were observed. To our knowledge this is the second pediatric case of fibroepithelial urethral polyp treated by HOLMIUM laser.

A not so harmless mass: Kaposiform hemangioendothelioma complicated by a Kasabach-Merritt phenomenon.

A vascular mass localized in the face and the neck was displayed by ultrasonography in a 38-week-old male fetus. At birth, the mass was bulky and purplish. The newborn breathed spontaneously but with severe desaturation.

Satellite DNA at the Centromere is Dispensable for Segregation Fidelity.

The typical vertebrate centromeres contain long stretches of highly repeated DNA sequences (satellite DNA). We previously demonstrated that the karyotypes of the species belonging to the genus are characterized by the presence of satellite-free and satellite-based centromeres and represent a unique biological model for the study of centromere organization and behavior. Using horse primary fibroblasts cultured in vitro, we compared the segregation fidelity of chromosome 11, whose centromere is satellite-free, with that of chromosome 13, which has similar size and a centromere containing long stretches of satellite DNA.

Epigenetics in cancer therapy and nanomedicine.

The emergence of nanotechnology applied to medicine has revolutionized the treatment of human cancer. As in the case of classic drugs for the treatment of cancer, epigenetic drugs have evolved in terms of their specificity and efficiency, especially because of the possibility of using more effective transport and delivery systems. The use of nanoparticles (NPs) in oncology management offers promising advantages in terms of the efficacy of cancer treatments, but it is still unclear how these NPs may be affecting the epigenome such that safe routine use is ensured.

Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer.

We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, = 5), in combination with bevacizumab (cohort 2, = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events.

Benefits of Retroperitoneoscopic Surgery in Pediatric Urology.

Purpose Of Review: The aim of this review is to find out the benefits of retroperitoneoscopy for the most common urological diseases in children.

Recent Findings: The emergence of minimally invasive surgery about 20 years ago revolutionized pediatric urology. In this context, laparoscopy and later retroperitoneoscopy were developed and applied to a wide spectrum of urological diseases.