Different titanium surfaces modulate the bone phenotype of SaOS-2 osteoblast-like cells.

Commercially pure titanium implants presenting a relatively smooth, machined surface or a roughned endosseous surface show a large percentage of clinical successes. Surface properties of dental implants seem to be important with respect to bone cells response. Implant topography appears to modulate cell growth and differentiation of osteoblasts affecting the bone healing around the titanium implant. The aim of the present study was to examine the effects of three different titanium surfaces on cell morphology, adhesion and bone phenotypic expression of human osteoblast-like cells, SaOS-2. SaOS-2 cells were cultured on commercially pure titanium disks of 1 cm in diameter with three different surface roughness: smooth (S), sandblasted (SB) and titanium plasma sprayed (TPS). Differences in the cell morphology were found on the three surfaces showing an uniform monolayer of shaped cells on the S surfaces, and clusters of multilayered cells with an irregular shape on the rough surfaces. The adhesion of SaOS-2 cells, as measured after 3h of culture, was not affected by surface roughness. ECM components such as collagen I (CoI), fibronectin (FN), vitronectin (VN) and tenascin (TN) were secreted and organized only on SB and TPS surfaces while on S surfaces they remained in the cytoplasm. Osteopontin and BSP-II were largely detected on SB and TPS surfaces, while only minimal production was observed on S surfaces. These data show that titanium surface roughness affects bone differentiation of osteoblast like-cells, SaOS-2, indicating that surface properties may be able to modulate the osteoblast phenotype. These observations also suggest that the bone healing response around dental implants can be affected by surface topography

Effects of physical exercise on adiponectin, leptin, and inflammatory markers in childhood obesity: systematic review and meta-analysis

Background: New findings on adipose tissue physiology and obesity-Associated inflammation status suggest that modification of the adipokine level can be relevant for the long-Term prevention of obesity-Associated chronic disease. Objectives: The scope of the present study was to investigate the effectiveness of physical exercise in reducing the systemic inflammation related to obesity in children. Methods: We conducted a systematic review with meta-Analysis of controlled randomized trials, identified through electronic database search, which investigated the effect of physical exercise, without concomitant dietary intervention, on adiponectin, leptin, and/or other inflammatory markers in children up to age 18 years with a body mass index greater than the 95th percentile for age and sex. Results: Seven trials were included in the meta-Analysis, with a total of 250 participants. Compared with the control group without any lifestyle modification, the physical exercise resulted in a reduction in leptin [standardized mean difference (SMD)-1.13; 95% confidence interval (95%CI):-1.89 to-0.37; I2 = 79.9%] and interleukin-6 (SMD-0.84; 95%CI:-1.45 to-0.23, I2 = 0.9%) and an increase in adiponectin plasma concentration (SMD 0.69; 95%CI: 0.02-1.35; I2 = 74.3%). Conclusions: These results indicate that physical exercise improved the inflammatory state in children with obesity. It is unclear whether this effect can reduce the risk of cardiovascular and metabolic disease in adulthood. Clinical trials with a uniform intervention protocol and outcome measurements are required to put our knowledge on adipose tissue biology into a clinical perspective

Non-modified RNA-Based Reprogramming of Human Dermal Fibroblasts into Induced Pluripotent Stem Cells

The generation of pluripotent stem cells from adult somatic cells by cell reprogramming has put a whole new perspective on stem cell biology and stem cell-based regenerative medicine. Cell reprogramming acts through the introduction of key genes that regulate and maintain the pluripotent cell state. In this chapter, we describe the optimized protocol for the efficient isolation of fibroblasts from a skin punch biopsy and the subsequent easy and effective generation of integration-free induced pluripotent stem cell (iPSC) colonies forcing the expression of specific factors by non-modified RNAs. © 2021, Springer Science+Business Media, LLC

In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts.

The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR.The amount of proteins characteristic for cardiac cells (alpha-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively) inclines toward an increase in both alpha-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart

Acute portal vein thrombosis precipitated by indomethacin in a HCV-positive elderly patient

BACKGROUND: An increased risk of venous thromboembolism has been reported in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We describe a case of acute portal vein thrombosis (PVT) in a hepatitis C virus (HCV)-positive elderly patient following administration of indomethacin. CASE PRESENTATION: A 79-year-old HCV-positive man was hospitalized for severe abdominal pain, nausea and vomiting, 15 days after starting indomethacin for back pain. Clinical signs and imaging evaluations disclosed a picture of PVT. Indomethacin was discontinued, and the patient was started on fondaparinux and antithrombin. He was discharged 15 days later due to improvement of his clinical conditions. Thirty days later, a follow-up ultrasound did not show appreciable signs of PVT. The time elapsing between the start of analgesic therapy and PVT onset suggests a role of indomethacin as the triggering agent. Indomethacin could have precipitated PVT by a combination of at least two detrimental mechanisms: 1) direct action on liver vascular endothelium by inhibition of prostacyclin biosynthesis; 2) damage to the intestinal mucosa, followed by inflammatory and pro-coagulant activation of portal endothelium upon exposure to bacterial endotoxins. CONCLUSIONS: This case can be of interest to physicians, who should exert caution when prescribing NSAIDs for inflammatory pain in patients with background inflammatory dysfunctions of the portal vein endothelium

Metabolic Reprogramming of Cancer Associated Fibroblasts: The Slavery of Stromal Fibroblasts

Cancer associated fibroblasts (CAFs) are the main stromal cell type of solid tumour microenvironment and undergo an activation process associated with secretion of growth factors, cytokines, and paracrine interactions. One of the important features of solid tumours is the metabolic reprogramming that leads to changes of bioenergetics and biosynthesis in both tumour cells and CAFs. In particular, CAFs follow the evolution of tumour disease and acquire a catabolic phenotype: in tumour tissues, cancer cells and tumour microenvironment form a network where the crosstalk between cancer cells and CAFs is associated with cell metabolic reprogramming that contributes to CAFs activation, cancer growth, and progression and evasion from cancer therapies. In this regard, the study of CAFs metabolic reprogramming could contribute to better understand their activation process, the interaction between stroma, and cancer cells and could offer innovative tools for the development of new therapeutic strategies able to eradicate the protumorigenic activity of CAFs. Therefore, this review focuses on CAFs metabolic reprogramming associated with both differentiation process and cancer and stromal cells crosstalk. Finally, therapeutic responses and potential anticancer strategies targeting CAFs metabolic reprogramming are reviewed

Musculocutaneous nerve variations. Meta-analysis of proportions and proposal for categorization

The musculocutaneous nerve (MCN) is one of the main terminal branches of the brachial plexus. It provides motor innervation to coracobrachialis, biceps brachii and brachialis muscles and sensory innervation to the skin of lateral side of the forearm. In the normal anatomical description, the MCN arises from lateral cord and don’t have communication with other terminal branches of brachial plexus. All motor branches arises from MCN, directly.[1] Despite these considerations, several variations of MCN have been reported. The most common are anomalous communications between MCN and median nerve. These communications could be relevant in clinical practice and could have several practical considerations that should be evaluated in different medical area, such as orthopedic surgery, traumatology or neurophysiology. Several classifications have been proposed but none of these is able to cover all aspects of this variation. Therefore, the aim of the present study are a systematic review of the available literature about MCN variations and a meta-analytic approach to define their prevalence.[2] At the same time, a new model of categorization with practical effects on clinical reasoning has been proposed. Several electronic databases have been searched. Articles have been screened and papers with anatomical description of MCN variations have been included. 43 out of 661 articles fulfilled inclusion criteria, with a description of 4695 brachial plexuses dissections. The random pooled prevalence of MCN variations is 18% (95%CI: 15-21%). The new categorization proposal is based on a 3 areas model: Area 1 (1A: absence of musculocutaneous nerve, 1B: variations before the division of the musculocutaneous nerve from lateral cord); Area 2: variations between origin of MCN from lateral cord and point of in coracobrachialis muscle (or same level if MCN does not pierce the muscle); Area 3: variations distal to point of entry in coracobrachialis muscle; Mixed areas: variations reported in more than a single area described above. Applying this model, the random pooled prevalence of reported variations is: Area 1A: 19% (95%CI: 11-28%), Area 1B: 26% (95%CI: 14-39%), Area 2: 46% (95%CI: 33- 59%), Area 3: 55% (95%CI: 40-70%), Mixed areas: 16 (95%CI: 8-25%). Therefore, MCN variations have a high prevalence. Among them, the most frequent are localized distal to coracobrachialis muscle. These results could be useful in clinical practice to point the attention at this anatomical region where variations in MCN are very common

Flatfoot in children: anatomy of decision making

Concern about a child’s foot posture is a common reason for frequent consultations for an array of health care professionals; sports medicine specialists are often the first to recognize and advise on foot pathology. In the decision making process, it is essential to distinguish between the different types of flatfoot deformity: paediatric or adult, congenital or acquired, flexible or rigid. Although flatfoot in children is a common finding, evidence for the techniques of the reliable and reproducible assessment of the foot posture is scant. This general review presents the factors involved in the forming and supporting of the foot arches, discusses the protocols useful in the evaluation of the foot posture, and indicates how to differentiate between flatfoot cases needing treatment and cases that need only reassurance

Anemia and iron in internal medicine: an Italian survey and a review on iron intravenous therapy in medical patients

In Italy, Internal Medicine Units hospitalize approximately 1,300,000 patients, often elderly and comorbid. The prevalent diagnoses are respiratory diseases, heart failure, or pneumonia. As a matter of fact, anemia is probably underestimated in the compilation of the official discharge forms (SDO) according to ICD-9 diagnostic codes. We promoted a survey among the Members the Italian Scientific Society of Internal Medicine (FADOI) with the aim to investigate the prevalence of anemia and iron deficiency, over than certain aspects related to the therapeutic management of patients with anemia. Furthermore, we performed a review summarizing current evidence for iron intravenous therapy in these patients. According to the survey, anemia is present in around half of the patients hospitalized in Internal Medicine, and about a quarter of them shows iron metabolism alterations. In the evaluation of iron metabolism, the dosage of ferritin is the most requested exam, whereas transferrin saturation is less considered. By focusing on some categories of patients, the awareness of the usefulness of intravenous iron therapy in patients with heart failure seems to be sufficiently common (76% of physicians), while it seems lower (60%) in the management of patients with chronic kidney disease (CKD) and anemia. Finally, more than 75% of the physicians answered that, in their hospital, there are few outpatients' offices or diagnostic pathways dedicated to patients with anemia. Anemia due to absolute or functional iron deficiency is particularly prevalent in Internal Medicine inpatients. For this reason, an accurate evaluation of iron profile and an adequate iron therapy is mandatory in these patients. Recent studies show that, in patients with heart failure, intravenous iron therapy is an effective way of improving patients' health, regardless of the presence of anemia. Similarly, iron therapy results fundamental to optimize erythropoiesis-stimulating agent efficacy in patients with chronic renal failure. In the next future, other therapeutic aspects of intravenous iron therapy will be probably clarified by several interesting ongoing studies focused on these patients

Generation of spheroids from human primary myofibroblasts: an experimental system to study myofibroblasts deactivation

Fibroblasts represent a heterogeneous cell population, that in adult body maintains the homeostasis of the extracellular matrix (ECM) and can acquire an immunoregulatory phenotype. Indeed, activated fibroblasts produce large amounts of cyclooxygenase-2 (COX-2) and proinflammatory cytokines (1). The activation of fibroblasts is represented by their differentiation into myofibroblasts. This process, either in wound healing or cancer tissue, is associated with the expression of alpha-smooth muscle actin (alpha-SMA), increased levels of growth factors and ECM-degrading proteases (2). Moreover, myofibroblasts form clusters in wound healing process and hypertrophic scars. In particular, cell clusters of hypertrophic scars are represented by nodules of myofibroblasts (3). It is known that human dermal fibroblasts established from neonatal foreskin, and forced in vitro to form clusters named spheroids, are activated to produce massive amounts of COX-2, prostaglandins and proinflammatory cytokines: this process leads to a programmed necrosis, designated “nemosis” (1). In the present study we generated spheroids from human primary myofibroblasts of skin, to evaluate necrotic, inflammation and activation markers during myofibroblasts clustering. Western blotting analysis, showing low levels of COX-2 and a significant decrease of alpha-SMA in protein extracts of spheroids, led to hypothesize that myofibroblasts have undergone a deactivation process within spheroids. This hypothesis is confirmed by cytostatic effect exerted by spheroids conditioned medium on both normal and cancer cell lines, by confocal immunofluorescence analysis of connexin 43 and immunohistochemical evaluation of proliferation marker Ki-67. This work could represent an experimental model to study myofibroblasts deactivation and highlights an alternative process regulating the turnover of myofibroblasts