In vitro effect of hCG on cryptorchid patients' gubernacular cells: a predictive model for adjuvant personalized therapy.

Background: Cryptorchidism is the absence of one or both testicles in the scrotum at birth, being a risk factor for testis cancer and infertility. The most effective method to treat cryptorchidism is orchiopexy, followed by human chorionic gonadotropin (hCG) therapy; however, a portion of treated patients do not show a significant improvement in testis volume and vascularization after adjuvant therapy.

Methods: In this study, we generated an in vitro model to predict the patient response to hCG by cultivating and treating primary cells derived from five cryptorchid patients' biopsies of gubernaculum testis, the ligament that connects the testicle to the scrotum.

Platelet-rich plasma effects on in vitro cells derived from pediatric patients with andrological diseases.

Undescended testis and testicular torsion represent two frequent andrological diseases that affect the pediatric age. Despite these testicular disorders having different causes, they both negatively influence fertility in adulthood mainly due to the accumulation of reactive oxygen species (ROS), which represents the primary molecular damage underlying their long-term effects. The gold standard of treatment for both pathologies is surgery; however, it cannot guarantee an optimal fertility outcome in all clinical cases, underscoring the need to identify effective adjuvant therapies that may target the augmented ROS levels.

Long-Term Follow Up in Anti-Contactin-1 Autoimmune Nodopathy.

Objective: To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN).

Methods: Patients with anti-CNTN1 autoimmune nodopathy detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected.

In vitro obtainment of stem-like cells from gubernaculum testis biopsies of cryptorchid pediatric patients.

Testicular descent is a crucial event in male sexual development, and alterations in this process during gestation can lead to reduced fertility in adulthood. Cryptorchidism, i.e.

Joint modeling of longitudinal and survival data for the evaluation of the impact of irrigation systems on the time until the occurrence of phoma leaf spot in Arabica coffee plants.

Background: The coffee crop is prominent in Brazilian agriculture, making the country a global power in this area. One of the main concerns in the coffee sector is disease, which can affect coffee productivity and quality. Thus, it is important to evaluate the factors that may affect coffee quality and thus enhance the development of strategies to reduce coffee losses and costs and optimize production.

Evaluation of Anticancer Activity of Nucleoside-Nitric Oxide Photo-Donor Hybrids.

Herein, we report the synthesis of a new hybrid compound based on a 2'-deoxyuridine nucleoside conjugated with a NO photo-donor moiety (dU-t-NO) via CuAAC click chemistry. Hybrid dU-t-NO, as well as two previously reported 2'-deoxyadenosine based hybrids (dAdo-S-NO and dAdo-t-NO), were evaluated for their cytotoxic and cytostatic activities in selected cancer cell lines. dAdo-S-NO and dAdo-t-NO hybrids displayed higher activity with respect to dU-t-NO.

Characterization Methods for Nanoparticle-Skin Interactions: An Overview.

Research progresses have led to the development of different kinds of nanoplatforms to deliver drugs through different biological membranes. Particularly, nanocarriers represent a precious means to treat skin pathologies, due to their capability to solubilize lipophilic and hydrophilic drugs, to control their release, and to promote their permeation through the stratum corneum barrier. A crucial point in the development of nano-delivery systems relies on their characterization, as well as in the assessment of their interaction with tissues, in order to predict their fate under in vivo administration.

Microfluidic Fabricated Liposomes for Nutlin-3a Ocular Delivery as Potential Candidate for Proliferative Vitreoretinal Diseases Treatment.

Purpose: Proliferative vitreoretinal diseases (PVDs) represent a heterogeneous group of pathologies characterized by the presence of retinal proliferative membranes, in whose development retinal pigment epithelium (RPE) is deeply involved. As the only effective treatment for PVDs at present is surgery, we aimed to investigate the potential therapeutic activity of Nutlin-3a, a small non-genotoxic inhibitor of the MDM2/p53 interaction, on ARPE-19 cell line and on human RPE primary cells, as in vitro models of RPE and, more importantly, to formulate and evaluate Nutlin-3a loaded liposomes designed for ophthalmic administration.

Methods: Liposomes were produced using an innovative approach by a microfluidic device under selection of different conditions.

Orthotopic forelimb transplantation in a Yucatan minipig model: Anatomic and in vivo study.

Introduction: Above elbow transplants represent 19% of the upper extremity transplants. Previous large-animal models have been too distal or heterotopic, did not use immunosuppression and had short survival. We hypothesize that an orthotopic forelimb transplant model, under standard immunosuppression, is feasible and can be used to address questions on peri-transplant ischemia reperfusion injury, and post-transplantation vascular, immunologic, infectious, and functional outcomes.

New Insights into Metabolic Alterations and Mitochondria Re-Arrangements in Pancreatic Adenocarcinoma.

Among the most aggressive cancer types, pancreatic ductal adenocarcinoma (PDAC) represents one with the highest lethality due to its resistance to therapies and to the frequent metastatic spread [...

Mitochondrial Features of Mouse Myoblasts Are Finely Tuned by Low Doses of Ozone: The Evidence In Vitro.

The mild oxidative stress induced by low doses of gaseous ozone (O) activates the antioxidant cell response through the nuclear factor erythroid 2-related factor 2 (Nrf2), thus inducing beneficial effects without cell damage. Mitochondria are sensitive to mild oxidative stress and represent a susceptible O target. In this in vitro study, we investigated the mitochondrial response to low O doses in the immortalized, non-tumoral muscle C2C12 cells; a multimodal approach including fluorescence microscopy, transmission electron microscopy and biochemistry was used.

Mitochondrial Dynamics as Potential Modulators of Hormonal Therapy Effectiveness in Males.

Worldwide the incidence of andrological diseases is rising every year and, together with it, also the interest in them is increasing due to their strict association with disorders of the reproductive system, including impairment of male fertility, alterations of male hormones production, and/or sexual function. Prevention and early diagnosis of andrological dysfunctions have long been neglected, with the consequent increase in the incidence and prevalence of diseases otherwise easy to prevent and treat if diagnosed early. In this review, we report the latest evidence of the effect of andrological alterations on fertility potential in both young and adult patients, with a focus on the link between gonadotropins' mechanism of action and mitochondria.

An Innovative Fluid Dynamic System to Model Inflammation in Human Skin Explants.

Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies.

Ex Vivo Evaluation of Ethosomes and Transethosomes Applied on Human Skin: A Comparative Study.

In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% / and transethosomes based on phosphatidylcholine 0.

The rs1001179 SNP and CpG methylation regulate catalase expression in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an extremely variable clinical course. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course. Elucidating mechanisms regulating CAT expression in CLL is preeminent to understand disease mechanisms and develop strategies for improving its clinical management.

Higher fitness and competitive advantage of Pyricularia oryzae Triticum lineage resistant to QoI fungicides.

Background: Quinone outside inhibitor (QoI) fungicides have not been effective in controlling the wheat blast disease [Pyricularia oryzae Triticum lineage (PoTl)] in Brazil. The first report of resistance of PoTl to QoIs in this country occurred in 2015. This study aimed to test hypotheses about the changes in fitness parameters and competitive advantage of the QoI-resistant (R) PoTl isolate group compared to the sensitive (S) isolate group.

Prenylation Defects and Oxidative Stress Trigger the Main Consequences of Neuroinflammation Linked to Mevalonate Pathway Deregulation.

The cholesterol biosynthesis represents a crucial metabolic pathway for cellular homeostasis. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids, and other molecules such as ubiquinone. Furthermore, some intermediates of this metabolic system perform biological activity in specific cellular compartments, such as isoprenoid molecules that can modulate different signal proteins through the prenylation process.

Mitochondrial Elongation and OPA1 Play Crucial Roles during the Stemness Acquisition Process in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer with an overall 5-year survival rate of less than 9%. The high aggressiveness of PDAC is linked to the presence of a subpopulation of cancer cells with a greater tumorigenic capacity, generically called cancer stem cells (CSCs). CSCs present a heterogeneous metabolic profile that might be supported by an adaptation of mitochondrial function; however, the role of this organelle in the development and maintenance of CSCs remains controversial.

3-Bromo-Isoxazoline Derivatives Inhibit GAPDH Enzyme in PDAC Cells Triggering Autophagy and Apoptotic Cell Death.

A growing interest in the study of aerobic glycolysis as a key pathway for cancer-cell energetic metabolism, favouring tumour progression and invasion, has led to consider GAPDH as an effective drug target to specifically hit cancer cells. In this study, we have investigated a panel of 3-bromo-isoxazoline derivatives based on previously identified inhibitors of GAPDH (GAPDH). The compounds are active, to a different extent, as inhibitors of human-recombinant GAPDH.

Divergent Roles of Mitochondria Dynamics in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors; it is often diagnosed at an advanced stage and is hardly treatable. These issues are strictly linked to the absence of early diagnostic markers and the low efficacy of treatment approaches. Recently, the study of the metabolic alterations in cancer cells has opened the way to important findings that can be exploited to generate new potential therapies.

Ex Vivo Normothermic Perfusion of Human Upper Limbs.

Background: Ischemia-reperfusion injury remains a primary concern in upper extremity transplantation. Ex vivo normothermic perfusion (EVNP) enables near-physiological organ preservation, avoiding the deleterious effects of hypoxia and cooling. We investigated the effectiveness of human limb EVNP compared with static cold storage (SCS).

Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells.

Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha.

Metabolic Profiling of Skeletal Muscle During Ex-Vivo Normothermic Limb Perfusion.

Introduction: Ex vivo normothermic limb perfusion (EVNLP) provides several advantages for the preservation of limbs following amputation: the ability to maintain oxygenation and temperature of the limb close to physiological values, a perfusion solution providing all necessary nutrients at optimal concentrations, and the ability to maintain physiological pH and electrolytes. However, EVNLP cannot preserve the organ viability infinitely. We identified evidence of mitochondrial injury (swelling, elongation, and membrane disruption) after 24 hours of EVNLP of human upper extremities.

Effects of CD20 antibodies and kinase inhibitors on B-cell receptor signalling and survival of chronic lymphocytic leukaemia cells.

Recently, clinical trial results have established inhibitors of B-cell receptor (BCR)-associated kinase (BAKi), with or without CD20 moniclonal antibodies (mAbs), as the preferred first-line treatment for most chronic lymphocytic leukaemia (CLL) patients. Using phosphospecific flow cytometry, we showed that in leukaemic cells from CLL patients the CD20 therapeutic antibodies - rituximab, ofatumumab, and obinutuzumab - inhibited BCR signalling pathways targeting preferentially pBTK - but not BTK - and pAKT. On the contrary, ibrutinib and idelalisib reduced pBTK to a higher extent than pBTK .