Biological Activities of Citrus-Derived Extracellular Vesicles on Human Cells: The Role of Preservation.

Extracellular vesicles (EVs) have been identified as important mediators for cell-to-cell communication. Citrus-based EVs in particular offer an excellent platform for nutraceutical delivery systems, as their endemic cargo includes micronutrients (e.g., ascorbic acid), which contribute to their antioxidant capacity. Despite being extensively investigated as to their therapeutic and diagnostic potential, their cargo is inherently unstable and thus directly affected by their storage and preservation. In this study, EVs were isolated from citrus fruit using tangential flow filtration and evaluated for their physicochemical characteristics, antioxidant activity and effects on human cells. To assess how their isolation and preservation methods affect these properties, the EVs were tested immediately after isolation (from fresh and freeze-thawed juices) or following freeze-drying. A measurable biological effect of cryoprotection on citrus-derived EVs was evident, whether during or after isolation. This was more pronounced in the cell-based assays, ranging from -4% to +32% in human skin fibroblast proliferation. Nevertheless, the effects on human cancer cells varied depending on the cell line. Although these results should be considered preliminary observations, subject to further investigation, it is safe to state that any type of preservation is expected to impact the EVs' biological activity.

A rare case of poorly differentiated mixed neuroendocrine-nonneuroendocrine tumor of the caecum with long term survival: A case report.

A 59-year-old woman presented with flushing attacks accompanied by tachycardia and hypotension, which lasted approximately 30 to 60 minutes, underwent 18 years ago a gastrointestinal tumor resection. The histologic examination revealed a poorly differentiated mixed neuroendocrine/adenocarcinoma located in the caecum with regional metastases. Postoperatively, the patient received combined chemotherapy of 5-fluorouracil with interferon for six months and since has remained asymptomatic. Her examination revealed positivity for chromogranin A (CgA) and a-Fetoprotein (aFP) (580 ng/24 h, normal range 27-94, and 10 IU/mL, normal range 0-6, respectively). Urinary 5-hydroxy indole acetic acid excretion was remarkably high (41.8 mg/24 h, normal range 2-10 mg/24 h). An abdominal Magnetic Resonance Imaging scan revealed multiple focal loci in the liver whose histological examination revealed a carcinoid tumor confirmed by an Octreoscan. Additional uptake was noted on the right shoulder and the right sternum-clavicle joint confirmed by Tc-99m MDP scan. The patient received somatostatin analogue therapy followed by long-acting release octreotide analogue therapy (30 mg/month) showing a partial improvement of relevant biomarkers. Two years later, carcinoid syndrome symptoms reappeared and due to the tumors expression of somatostatin receptors the patient received peptide receptor radionuclide therapy with 177Lu-DOTATATE that resulted in both clinical and biochemical improvements.

Evaluation of the Response of HOS and Saos-2 Osteosarcoma Cell Lines When Exposed to Different Sizes and Concentrations of Silver Nanoparticles.

Osteosarcoma is considered to be a highly malignant tumor affecting primarily long bones. It metastasizes widely, primarily to the lungs, resulting in poor survival rates of between 19 and 30%. Standard treatment consists of surgical removal of the affected site, with neoadjuvant and adjuvant chemotherapy commonly used, with the usual side effects and complications. There is a need for new treatments in this area, and silver nanoparticles (AgNPs) are one potential avenue for exploration. AgNPs have been found to possess antitumor and cytotoxic activity in vitro, by demonstrating decreased viability of cancer cells through cell cycle arrest and subsequent apoptosis. Integral to these pathways is tumor protein p53, a tumor suppressor which plays a critical role in maintaining genome stability by regulating cell division, after DNA damage. The purpose of this study was to determine if p53 mediates any difference in the response of the osteosarcoma cells in vitro when different sizes and concentrations of AgNPs are administered. Two cell lines were studied: p53-expressing HOS cells and p53-deficient Saos-2 cells. The results of this study suggest that the presence of protein p53 significantly affects the efficacy of AgNPs on osteosarcoma cells.

Biophysical interactions between components of the tumor microenvironment promote metastasis.

During metastasis, tumor cells need to adapt to their dynamic microenvironment and modify their mechanical properties in response to both chemical and mechanical stimulation. Physical interactions occur between cancer cells and the surrounding matrix including cell movements and cell shape alterations through the process of mechanotransduction. The latter describes the translation of external mechanical cues into intracellular biochemical signaling. Reorganization of both the cytoskeleton and the extracellular matrix (ECM) plays a critical role in these spreading steps. Migrating tumor cells show increased motility in order to cross the tumor microenvironment, migrate through ECM and reach the bloodstream to the metastatic site. There are specific factors affecting these processes, as well as the survival of circulating tumor cells (CTC) in the blood flow until they finally invade the secondary tissue to form metastasis. This review aims to study the mechanisms of metastasis from a biomechanical perspective and investigate cell migration, with a focus on the alterations in the cytoskeleton through this journey and the effect of biologic fluids on metastasis. Understanding of the biophysical mechanisms that promote tumor metastasis may contribute successful therapeutic approaches in the fight against cancer.

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management.

This review aims to explore, present, and discuss disorders of glucose metabolism implicated in pituitary gland diseases, the appropriate interventions, as well as the therapeutic challenges that may arise. Pituitary pathologies may dysregulate glucose homeostasis, as both the excess and deficiency of various pituitary hormones can affect glucose metabolism. Increased circulating levels of growth hormone, glucocorticoids or prolactin have been shown to mainly provoke hyperglycemic states, while hypopituitarism can be associated with both hyperglycemia and hypoglycemia. Addressing the primary cause of these disorders with the use of surgery, medical treatment or radiotherapy forms the cornerstone of current management strategies. Physicians should bear in mind that some such medications have an unfavorable effect on glucose metabolism too. When unsuccessful, or until the appropriate treatment of the underlying pituitary problem, the addition of established antidiabetic therapies might prove useful. Further studies aiming to discover more accurate and effective drug preparations in combination with optimal lifestyle management models will contribute to achieving a more successful glycemic control in these patients.

Endocrine approach in the treatment of obesity: Is there any space for the adiponectin action?

Adiponectin is a hormone secreted by adipose tissue, exerting many positive effects in the human body. Its action has been widely studied, placing it into the metabolic health beneficial products of the adipose tissue. Nevertheless, adiponectin has been shown to exert some extra beneficial non metabolic actions, as well. Adiponectin levels can be related to reduced incidence of cancer in obese patients. Moreover, adiponectin has been shown to be implicated in the positive fertility outcomes of women. Some new studies have also indicated that adiponectin has a potential effect in the control of appetite, which raises a question, whether adiponectin could be accredited to be useful in the endocrine evaluation of obesity. Could these additional non-metabolic actions prove its helpfulness?

The Effect of Clenching and Occlusal Instability on Body Weight Distribution, Assessed by a Postural Platform.

The purpose of this research project was to investigate whether or not clenching and occlusal instability of Angle's Class I malocclusion have an effect on body weight distribution in healthy adult subjects. Twenty adults (fourteen males and six females, ages 27-40, mean age 31.7 years, SD 3.32) were included in this study. The MatScan (Tekscan Inc., Boston, MA) system was used to measure the body weight distribution changes of the subjects. Four body weight distribution measurements were taken for each subject while (1) the mandible was in the rest position (no tooth contact) (RES), (2) subject was clenching (maximum intercuspation of the teeth with heavy occlusal forces) (CL), (3) subject was clenching on the right side (with 1 mm disocclusion on the left side) (CLR), and (4) subject was clenching on the left side (with 1 mm disocclusion on the right side) (CLL). The lateral and the anteroposterior body weight distribution changes during the different clenching conditions (both sides, right, and left) were compared to those at which the mandible was at the rest position. The statistical significance of these results was tested with a Chi-Squared test (p<0.05). Based on the findings of the present study it was concluded that clenching and occlusal instability are associated with lateral body weight distribution changes.

Oculo-Dento-Digital Dysplasia (ODDD) Due to a GJA1 Mutation: Report of a Case with Emphasis on Dental Manifestations.

Oculo-dento-digital dysplasia (ODDD) is a congenital disorder manifesting with multiple phenotypic abnormalities involving the face, eyes, teeth, and limbs in addition to neurologic symptomatology. This report aims to present a female patient with ODDD who was referred due to extensive oral restorative needs. The presence of hypoplastic enamel triggered further evaluation. Characteristic facies with hypoplastic alae nasi and syndactyly offered greater insight into the phenotype of the syndrome. Clinical suspicion was confirmed by genetic sequencing revealing heterozygous mutation in GJA1. It is important to be aware of genetic disorders associated with characteristic dental malformations to offer appropriate counseling and treatment.

In prostate cancer, low adiponectin levels are not associated with insulin resistance.

PURPOSE: Adiponectin, an adipose tissue-derived hormone with insulin-sensitizing effect, has been inversely associated with several hormonally dependent malignancies. Prostate cancer is associated with low levels of adiponectin, which have been proposed as an independent risk factor for this malignancy. Aim of this study was to examine whether hypoadiponectinaemia in prostate is associated with insulin resistance. EXPERIMENTAL DESIGN: Plasma samples and covariate data in the context of a case-control study of 300 Greek men were evaluated including 75 patients with prostate cancer, 75 patients with benign prostatic hyperplasia (BPH) and 150 age-matched healthy controls. RESULTS: Patients with prostate cancer had significantly lower plasma adiponectin levels compared with the other two groups, that is BPH patients and healthy controls (7.4 ± 5 ng/mL vs. 11.5 ± 6.4 ng/mL and 12.8 ± 8 ng/mL, respectively). On the other hand, no statistically significant differences were found between patients with prostate cancer and the other two groups for both HOMA-IR and QUICKI (P-value = 0.551). As expected, in all three groups, the levels of adiponectin correlated negatively with HOMA-IR (rho = -0.214, P-value = 0.006), QUICKI (rho = 0.214, P-value = 0.006) and insulin levels (rho = 0.942, P-value < 0.001). CONCLUSION: In spite of what would have been expected from the relevant literature, our data suggest that the hypoadiponectinaemia in prostatic cancer does not appear to be associated with insulin resistance.

The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review.

The aim of this narrative review is to provide current evidence for the interaction between obesity, metabolic syndrome (MS) and reproductive axis. Gonadotropin-releasing hormone (GnRH) pulses and, consequently, normal function of reproductive (hypothalamus-pituitary-gonadal) axis depend on normal energy balance, which presupposes sufficient food intake, reasonable energy consumption and average thermoregulatory costs. In case of an energy imbalance, reproductive dysfunction may occur. In young women, excessive leanness is accompanied by puberty delay, whereas premature puberty might be a manifestation of obesity. In a similar way, obesity in men affects fertility. Excess adipose tissue results in increased conversion of testosterone to estradiol, which may lead to secondary hypogonadism through reproductive axis suppression. Moreover, oxidative stress at the level of the testicular micro-environment may result in decreased spermatogenesis and sperm damage. Products of the adipocyte, such as leptin, adiponectin and resistin, and gut peptides, such as ghrelin, are considered to be crucial in the interaction between energy balance and reproduction. Finally, an indirect evidence for the interplay between MS and reproductive axis is the fact that when treating components of one, parameters of the other can be improved as well. These therapeutic interventions include lifestyle modifications, pharmacological agents, such as sex hormone replacement therapy, and surgical procedures. Although many issues remain unclear, the elucidation of the complex interaction between MS and reproductive axis will have obvious clinical implications in the therapeutic approach of both entities.

Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen.

INTRODUCTION: Ideally, there will be reproducible markers easily and non-invasively available to test for malignancy, or alternative procedures when there is no accurate marker available. For prostate cancer, one of the most common cancers in men, levels of prostate-specific antigen (PSA) lack specificity and sensitivity for the determination of malignancy when they fall within a range of values termed the 'grey zone'. OBJECTIVE: To examine the predictive value of sialic acid in prostate neoplasms. STUDY DESIGN: In our study of diagnostic accuracy we recruited 70 men complaining of urinary symptoms who presented in the urology department as outpatients or inpatients. All patients were checked with biopsy and pathology in order to relate benign and malignant lesions of the prostate to levels of sialic acid, a member of a family of acetylated products of neuraminic acid, which has so far proved to be a very sensitive and accurate marker of malignancy. RESULTS: The sialic acid level was found to be elevated in patients with prostate cancer (mean 75.06±10.4 mg/dl) and reduced in patients with benign prostate hyperplasia (mean 57.086±8.7 mg/dl) (p<0.01); it had a sensitivity of 86% and specificity of 84% in diagnosing malignancy. CONCLUSION: Sialic acid can be used as an adjunct in predicting prostate malignancy when PSA values fall in the grey zone.

Gut hormones and leptin: impact on energy control and changes after bariatric surgery--what the future holds.

Obesity is now considered the new world epidemic. In an attempt to face this menace to public health, several treatments, apart from the traditional nutritional modification and oral medication, have been introduced, among them bariatric surgery and gut hormone-based treatments. The gastrointestinal (GI) tract is a powerful endocrine organ, releasing active peptides and influencing appetite and glycaemic control. Alteration of the GI tract, in ways that exaggerate the secretion and levels of the gut hormones, creates a new functional equilibrium that further contributes to weight loss. The purpose of this review is to explore the mechanisms that drive this gut hormone-derived body regulation, as well as the changes that occur to them after bariatric surgery. Close to that, leptin, a hormone secreted by adipose tissue will be analysed, as its pathways are closely related to those of the gut hormones. Gut hormones are strongly implicated in energy control, and various effects of bariatric surgery in weight loss are directly related to the alteration of the levels of these hormones.

Immediately loaded maxillary and mandibular dental implants with fixed CAD/CAM prostheses using a flapless surgical approach: a clinical report.

Immediate implant loading is a viable treatment method for selected cases. One of the greatest advantages of this method is the virtual surgery, which precedes the actual clinical treatment and eliminates any need for last minute decisions. The actual surgery time is decreased, since all steps are predetermined. Additionally, no flaps have to be elevated, resulting in preservation of periimplant soft tissues, vascularization of the underlying bone, fewer postoperative complications, and minimal patient discomfort. This article presents a clinical approach made possible due to the evolution of modern scanning techniques and appropriate software.