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In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology and treatment of many diseases with traits that appear to be particularly relevant in influencing the outcomes of many morbid forms. Today, the inclusion of gender in biomedical research, to improve the scientific quality and scientific relevance of knowledge, of technology is an increasingly present element precisely due to the practical implications that derive from it. Gender differences describe the biological variability between women and men, which is, in turn, related to differences in the information contained in sex chromosomes, the specific gene expression of autosomes linked to sex, the different number and quality of sex hormones, and their different effects on systems and organs, without neglecting the fact that each of the sexes has different target organs on which these hormones act. Additionally, both genders undergo metabolic changes throughout their lives, and this is especially true for women who show more dramatic changes due to their role in reproduction. Gender differences are not only the result of our genetic makeup but are also mixed with socio-cultural habits, behaviors, and lifestyles, differences between women and men, exposure to specific environmental influences, different food and lifestyle styles or stress, or different attitude in compliance with treatments and disease prevention campaigns. Gender differences also affect behavior throughout life, and physical changes can have implications for lifestyle, social roles, and mental health. Therefore, determinism and therapeutic outcome in chronic diseases are influenced by a complex combination of biological and environmental factors, not forgetting that there are many interactions of social and biological factors in women and men. This review will address the role of gender differences in the management of various forms of diabetes and its complications considering the different biological functions of hormones, the difference in body composition, physiological differences in glucose and fat metabolism, also considering the role of the microbiota. intestinal, as well as the description of gestational diabetes linked to possible pathophysiological events typical of reproduction.

Citrus fruits are the main fruits of the Mediterranean diet and have been long recognized for their beneficial effects on human health. Observational studies have shown a significant association between dietary flavonoid intake and reduced risk of cardiovascular and malignant diseases. The beneficial effects of citrus fruits on human health appear to be due to their high content in vitamins, minerals and fibers. In particular, the antioxidant and anti-inflammatory activities have been indicated as some of the mechanisms through which citrus fruits may thwart the development of chronic degenerative diseases such as atherosclerosis and cancer. This review would critically examine the results from numerous experimental and clinical studies carried out in order assess the contribute of citrus flavonoids to the prevention of chronic pathological conditions including atherosclerosis and cancer.

Wrist circumference is a clinical marker for insulin-resistance in overweight/obese children and adolescents. Insulin resistance is considered a major determinant of increased vascular resistance and hypertension. The aim of the study was to investigate the association between wrist circumference and systolic (S) and diastolic (D) blood pressure (BP) in a population of overweight/obese children and adolescents. A population of 1133 overweight/obese children and adolescents (n = 1133) were consecutively enrolled. Multivariate regression analyses were used to investigate the influence of independent variables on the variance of BP. The prevalence of hypertension was 21.74% in males and 28.95% in females (p = 0.048). The results showed that SBP was significantly associated with wrist circumference in both genders (p < 0.0001 for both comparisons). We found no association between DBP and wrist circumference in either gender. Wrist circumference accounted for 17% of the total variance of SBP in males and 14% in females. Wrist circumference, a marker of insulin resistance, is associated with increased SBP in overweight/obese children and adolescents, suggesting a role of insulin resistance in the pathogenesis and development of hypertension.

Thyroid hormones have been proposed as anti obesity drugs due to their effects on basal metabolism and the ability to increase energy expenditure. However, their clinical use has been strongly curbed by the concomitant onset of thyrotoxicosis. In this setting, several studies have been undertaken to assess the role of 3,5 diiodo- L-thyronine (T2), an endogenous metabolite of thyroid hormone derived from the enzymatic deiodination of triodothyronine T3. The metabolic effects of T2 are similar to those induced by T3. However, these effects appear to involve different and not welldefined mechanisms that make this molecule clinically useful as potential drug in the treatment of pathological conditions such as obesity and hepatic steatosis. The main pharmacological target of T2 appears to be the mitochondria. Therefore, the administration of T2 to obese subjects might improve the mitochondrial performance, which is generally recognized to be reduced in these subjects who must oxidize greater quantities of substrates. In this context, it can be hypothesized that T2, by acting mainly on mitochondrial function and oxidative stress, might be able to prevent and revert the tissue damages and hepatic steatosis induced by a hyperlipidic diet and a concomitant reduction in the circulating levels LDL and triglycerides as well. This review the discuss the mechanisms of action of T2 and the possible, future clinical uses of T2 analogs for the treatment lipid dysmetabolism related to obesity and overweight.

Obesity is a chronic pathological condition with a multifactorial aetiology, characterised by an excessive body fat accumulation with multiple organ-specific consequences. Emerging evidence highlights that obesity appears to be associated with multiple alterations in the endocrine system. However, the mechanisms underlying the interactions between obesity and this system remain still controversial. This review discusses the impact of obesity on various endocrine systems and, in particular, would provide a general overview on the biochemical changes that may occur in each of these axes in association with obesity.

Adipose tissue secretes many adipokines that regulate important physiological functions. Growing studies have highlighted that these bioactive molecules may contribute to the development of metabolic and cardiovascular diseases. Adipokines exert systemic metabolic effects and independent activity on numerous cells of the cardiovascular system, including cardiomyocytes and vascular cell walls. Adiponectin shows anti-inflammatory and anti-atherosclerotic activity on blood vessels. Conversely, resistin is endowed with pro-inflammatory effects and stimulates the proliferation of smooth muscle cells, thus promoting the development of atherosclerotic plaque. Leptin plays an important role in cardiac remodeling and blood pressure regulation through the activation of the sympathetic system. Obesity is a pathological condition associated with hypertrophy of white adipose tissue, which stimulates the production of pro-inflammatory adipokines while, it reduces the production of anti-inflammatory adipokines. The delicate balance among the production of pro-and anti-inflammatory molecules generated by adipose tissue affects, not only the development of metabolic complications associated with obesity, but also the onset and progression of atherosclerosis. Therefore, adipokines may be regarded as potential agents of clinical interest in the treatment of a wide range of metabolic disorders and as potential biomarkers useful for early detection of metabolic, cardiovascular and inflammatory diseases.

Follistatin is a single-chain glycosylated protein whose primary function consists in binding and neutralizing some members of the transforming growth factor-β superfamily such as activin and bone morphogenic proteins. Emerging evidence indicates that this molecule may also play a role in the malignant progression of several human tumors including prostate cancer. In particular, recent findings suggest that, in this tumor, follistatin may also contribute to the formation of bone metastasis through multiple mechanisms, some of which are not related to its specific activin or bone morphogenic proteins’ inhibitory activity. This review provides insight into the most recent advances in understanding the role of follistatin in the prostate cancer progression and discusses the clinical and therapeutic implications related to these findings.

Cathepsin D is a lysosomal acid proteinase which is involved in the malignant progression of breast cancer and other gynecological tumors. Clinical investigations have shown that in breast cancer patients cathepsin D overexpression was significantly correlated with a shorter free-time disease and overall survival, whereas in patients with ovarian or endometrial cancer this phenomenon was associated with tumor aggressiveness and a degree of chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate the role and the prognostic value of cathepsin D also in other solid neoplasms. However, conflicting results have been generated from these studies. The discrepancies in these results may, in part, be explained with the different methodological approaches used in order to determine the levels of expression of the enzyme in tumor tissues and body fluids. Further investigations using well-standardized techniques may better define the clinical significance of cathepsin D expression in solid tumors. Nevertheless, evidence emerging from these studied indicates that this proteinase seems to facilitate early phases of tumor progression such as cell proliferation and local dissemination. These findings support the concept that cathepsin D may be a useful marker for identifying patients with highly malignant tumor phenotypes who may need more aggressive clinical treatment; this enzyme may also be considered as a potential target for a novel therapeutic approach in the treatment of solid neoplasms.

In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2–L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.