Sperm Mesoderm Specific Transcript Gene Methylation Status in Infertile Patients: A Systematic Review and Meta-Analysis.

PURPOSE: The mesoderm specific transcription (MEST) gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on MEST methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the MEST gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters. MATERIALS AND METHODS: This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating MEST gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. RESULTS: Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of MEST gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360). CONCLUSIONS: Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The MEST gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.

Productivity Index in Clinical Andrology: Research Directions on High-Impact Topics and in Particular on Male Infertility.

PURPOSE: Andrological diseases have an important social and economic impact as they cause a serious impairment of the quality of life of the affected patient. Epidemiologically, the impact of these disorders is progressively increasing, as demonstrated by the ever-growing prevalence of male infertility. This evidence justifies the rapid development of research in andrology that the scientific community has undertaken in recent decades. This study aims to evaluate the productivity index of the main andrological topics studied and reported in the literature. METHODS: The total number of published articles was extracted from the Scopus database by entering the following keywords and mesh terms: "Male Infertility", "Erectile Dysfunction", "Premature Ejaculation", "Male Hypogonadism", "Testicular Tumors", "Prostate Cancer", "Prostatic hyperplasia", "Prostate hyperplasia", "Prostatitis", "Prostate inflammation", and "Male Accessory Gland Infections". Furthermore, a list of the top 50 researchers sorted by productivity was created for each topic. For male infertility, a further search was performed by combining the search term "male infertility" with the above-mentioned terms. Thus, a list of the top 30 authors in order of productivity was also extracted. The graphs were created using Excel. RESULTS AND CONCLUSIONS: As could be expected, we observed that prostate cancer and male infertility were the two most investigated topics, followed by benign prostatic hyperplasia and erectile dysfunction, whose prevalence is set to increase given the progressive aging of the population. Less investigated is the inflammation of the accessory sexual glands. In conclusion, this study provides a ranking of the main andrological topics investigated in the literature, also presenting the top list of the most productive authors for each one.

Risk Factors for Hypoparathyroidism after Thyroid Surgery: A Single-Center Study.

BACKGROUND: Hypoparathyroidism is one of the most common complications after thyroidectomy. This study evaluated the incidence and potential risk factors for postoperative hypoparathyroidism after thyroid surgical procedures in a single high-volume center. METHODS: In this retrospective study, in all patients undergoing thyroid surgery from 2018 to 2021, a 6 h postoperative parathyroid hormone level (PTH) was evaluated. Patients were divided into two groups based on 6 h postoperative PTH levels (≤12 and >12 pg/mL). RESULTS: A total of 734 patients were enrolled in this study. Most patients (702, 95.6%) underwent a total thyroidectomy, while 32 patients underwent a lobectomy (4.4%). A total of 230 patients (31.3%) had a postoperative PTH level of <12 pg/mL. Postoperative temporary hypoparathyroidism was more frequently associated with female sex, age < 40 y, neck dissection, the yield of lymph node dissection, and incidental parathyroidectomy. Incidental parathyroidectomy was reported in 122 patients (16.6%) and was correlated with thyroid cancer and neck dissection. CONCLUSIONS: Young patients undergoing neck dissection and with incidental parathyroidectomy have the highest risk of postoperative hypoparathyroidism after thyroid surgery. However, incidental parathyroidectomy did not necessarily correlate with postoperative hypocalcemia, suggesting that the pathogenesis of this complication is multifactorial and may include an impaired blood supply to parathyroid glands during thyroid surgery.

Effects of the ketogenic diet on bone health: A systematic review.

Objective: To carry out a systematic review of published studies to evaluate the relationship between different type of ketogenic diet (KD) and bone health as supported by the scientific literature. Methods: The study involved all articles that assessed the relationship between the use of KD for the treatment of overweight or obesity and bone health. The quality assessment was evaluated with using the Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: "osteoporosis", "bone health, "bone function", "bone mineral density", and "ketogenic diet". Results: Seven trials were identified and reviewed. No significant changes in bone mass density (BMD) were observed after KD. The results showed no significant effect on bone resorption by measuring urinary N-telopeptide levels, on bone formation by measuring bone-specific alkaline phosphatase, or alterations in overall bone turnover in patients who followed KD. Only in female subject after a 10% weight loss, bone resorption increases while new bone synthesis decreases, but without increasing the risk of osteoporosis. Finally, patients on KD lost significantly more weight than controls, associated with an increase in serum vitamin D levels and a reduction in plasma parathyroid hormone (PTH) levels. Conclusion: No human studies have currently been conducted with adequate and powerful experimental designs to definitively understand the impact of KD therapy on bone health.

Globozoospermia: A Case Report and Systematic Review of Literature.

PURPOSE: Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize the oocyte. In this article, we present the clinical case of a young globozoospermic patient with a new, not yet described mutation of the DPY19L2 gene. We also performed a systematic review of the literature on gene mutations, the outcome of assisted reproductive techniques, and the risk of transmission of abnormalities to the offspring in patients with globozoospermia and made recommendations to offer a more appropriate clinical management of these patients. MATERIALS AND METHODS: We performed a systematic search in the PubMed, Google Scholar, and Scopus databases from their inception to December 2021. The search strategy included the combination of the following Medical Subjects Headings (MeSH) terms and keywords: "globozoospermia", "round-headed spermatozoa", "round head spermatozoa", "intracytoplasmic sperm injection", "ICSI", "offspring", "child health", "assisted reproductive technique outcome". All the eligible studies were selected following the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model. The quality of included studies was assessed by applying the "Cambridge Quality Checklists". RESULTS: The main genes involved in the pathogenesis of globozoospermia are DPY19L2, SPATA16, PICK1, GGN, SPACA1, ZPBP, CCDC62, and CCNB3 genes. Other genes could also play a role. These include C2CD6, C7orf61, CCIN, DNH17, DNH6, PIWIL4, and CHPT1. Globozoospermic patients should undergo ART to achieve fertility. In particular, intracytoplasmic sperm injection with assisted oocyte activation or intracytoplasmic morphologically-selected sperm injection appears to be associated with a higher success rate. Patients with globozoospermia should also be evaluated for the high rate of sperm aneuploidy which appears to influence the success rate of ART but does not appear to be associated with an increased risk of transmission of genetic abnormalities to offspring. CONCLUSIONS: This systematic review summarizes the evidence on the gene panel to be evaluated, ICSI outcomes, and the health of the offspring in patients with globozoospermia. Evidence-based recommendations on the management of patients with globozoospermia are provided.

Lipidomic Profile of Human Sperm Membrane Identifies a Clustering of Lipids Associated with Semen Quality and Function.

Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.

Ultrastructural Sperm Flagellum Defects in a Patient With CCDC39 Compound Heterozygous Mutations and Primary Ciliary Dyskinesia/Situs Viscerum Inversus.

Introduction: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease characterized by structural or functional motile cilia abnormalities. Up to 40 different genes seem, at the moment, to be involved in the pathogenesis of PCD. A number of ultrastructural defects have also been reported in sperm flagella, but the sperm mitochondrial membrane potential (MMP) has never been described in these cases. Aim: The aim of this study was to report the sperm MMP and ultrastructural abnormalities of the sperm flagella found in a patient with PCD and situs inversus (Kartagener syndrome) and its characterization from the genetic point of view. Methods: Transmission electronic microscopy (TEM) analysis was used to evaluate flagella ultrastructure. The genetic testing was performed by next-generation sequencing. Sperm DNA fragmentation and MMP were also evaluated by flow cytometry. Results: We report here the case of an 18-year-old male patient with PCD and situs inversus and severe oligo-astheno-teratozoospermia. TEM analysis of his spermatozoa showed an abnormal connecting piece. The mid piece appeared abnormally thickened, with cytoplasmic residue, dysplasia of fibrous sheath, loss of the outer dynein arms (ODAs), truncated inner dynein arms, and supernumerary outer fibers. The percentage of spermatozoa with fragmented DNA was normal, whereas a high percentage of spermatozoa had low MMP, suggesting an altered mitochondrial function. The genetic analysis showed the presence of c.610-2A > G, p.Arg811Cys compound heterozygous mutations in the CCDC39 gene. Conclusion: The case herein reported suggests that the high percentage of sperm with low MMP may play a role in the pathogenesis of asthenozoospermia in patients with Kartagener syndrome. In addition, we report, for the first time, the missense variant p.Arg811Cys in the CCDC39 gene in a patient with Kartagener syndrome. Although in silico analysis predicts its damaging potential, its clinical meaning remains unclear.

Gonadal Steroids and Sperm Quality in a Cohort of Relapsing Remitting Multiple Sclerosis: A Case-Control Study.

Introduction: Evaluation of the hypothalamic-pituitary-testicular axis and sperm analyses are not a standard examination of patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Methods: This is a prospective-case-controlled study. Patients, aged 18-55, with a confirmed diagnosis of RRMS, naïve to any DMT were enrolled. Controls were men with normal evaluation who acceded to the Andrology Center of Catania in a contemporary matched randomized fashion to the group of RRMS patients. The aim of the study is to evaluate gonadal steroids and sperm quality in men at the time of RRMS diagnosis and 12 months following the first disease modifying treatment (DMT). Results: Out of 41 patients with RRMS, 38 were included in the study (age 40.3 ± 12.3) to be compared with matched controls. Patients with RRMS showed no differences in gonadal steroids or sperm parameters, except for free testosterone (fT) plasma levels, which were lower in RRMS patients than controls (median 0.09 vs. 1.4, p < 0.0001). The correlation analyses, corrected for age and Body Mass Index, did not reveal any correlation between hormonal/sperm parameters and level of disability or disease activity at onset. Additionally, 12 months following the start of DMT, there were no differences in gonadal steroids and sperm quality compared to baseline. Conclusions: Results suggest that RRMS may not have an impact on fertility status but prospective long-term studies are needed.

Evaluation of seminal fluid leukocyte subpopulations in patients with varicocele.

Varicocele is a common cause of sperm damage. Some studies showed higher concentration of seminal leukocytes in patients with varicocele. The aim of the study was to evaluate seminal leukocyte subpopulations in patients with varicocele. We enrolled 20 patients with varicocele and 20 age-matched healthy men. Sperm analysis was conducted according to the World Health Organization (WHO) 2010 criteria. We evaluated seminal leukocyte subpopulations and bio-functional sperm parameters by flow cytometry. Patients with varicocele had significantly lower sperm concentration and total number than controls. Regarding seminal leukocyte subpopulations, patients with varicocele had a significantly lower percentage of CD8+ and CD16+ leukocytes and a significantly higher percentage of CD4+ leukocytes than controls. As for bio-functional sperm parameters, we found that patients with varicocele had a significantly lower percentage of alive spermatozoa compared to the control group. These results may explain the increased level of cytokines in the seminal plasma of patients with varicocele.

Dual-release hydrocortisone for treatment of adrenal insufficiency: a systematic review.

Dual-release hydrocortisone is a new hydrocortisone formulation developed to improve the pharmacokinetic and the pharmacodynamic profiles and patient compliance. The aim of this review is to summarize the main knowledge on dual-release hydrocortisone, with particular attention to pharmacokinetics, metabolic and health-related quality-of-life aspects, bone health and drug safety.

Early male aging or poor clinical consideration for males in IVF centers? An original study.

The Italian law 40/2004 allows the use of assisted reproduction techniques only if there are no other effective therapeutic approaches to overcome infertility. According to article 4 paragraph 1, the impossibility of removing the otherwise impeding causes to achieve a pregnancy must be ascertained before the couple undergoes assisted reproduction techniques. On this premises, we sought to evaluate the percentage of couples who underwent or were addressed to assisted reproduction techniques despite a known and potentially treatable male infertility factor in fertility centers in the city of Catania, Italy. To accomplish this, andrologists, urologists and endocrinologists were asked to report the number of couples already addressed to assisted reproduction techniques which they counseled in the trimester April-June 2018 having a under 35-year-old female partner and at least one among the following untreated conditions: (A) oligoasthenoteratozoospermia and FSH <8 mIU/ml, (B) third-degree varicocele (mono or bilateral form), and (C) leukocytospermia or urogenital infections. Of the 320 enrolled couples, 75 (23%) met the criterion A, 45 (14%) the criterion B, and 62 (19%) the criterion C. More than a half couples were addressed to assisted reproduction techniques despite a potentially treatable male infertility factor.

Effect of treatment with testosterone on endothelial function in hypogonadal men: a systematic review and meta-analysis.

Despite several studies showing an inverse correlation of total testosterone with endothelial damage, the effect of testosterone replacement therapy (TTh) on endothelial function has been scarcely investigated. In order to systematically assess the relationship between endothelial dysfunction and TTh, we performed a review and meta-analysis of available prospective and cross-sectional studies. A thorough research was performed on MEDLINE for hypogonadism and endothelial dysfunction. We retrieved 28 papers, among which 23 were excluded for different reasons: five papers accounting for six studies (two crossover randomized clinical trial (RCT), three observational, one placebo controlled RCT) were therefore included in analysis. Overall, 86 patients with hypogonadism were included in analysis (mean age 49.57 ± 8.85 years). Baseline total testosterone serum levels were 8.11 ± 2.42 nmol/L and significantly increased while undergoing TTh (standard mean difference (SMD) 2.93 nmol/L, 95% confidence interval (CI) 1.89:3.97, p < 0.001). Due to the paucity of studies available, flow-mediated dilation (FMD) was chosen as the best surrogate marker of endothelial dysfunction. FMD did not significantly change after testosterone administration (SMD -0.22, 95% CI -1.29:0.84, I2 = 90%); acute testosterone administration was associated with an increase in FMD, whereas a reduction in FMD emerged following chronic treatment, but statistical significance was not reached for both effects. This is the first meta-analysis study assessing the influence of TTh on endothelial function; however, results are far from conclusive, as proven by the high heterogeneity.

Accuracy of the Low-Dose ACTH Stimulation Test for Adrenal Insufficiency Diagnosis: A Re-Assessment of the Cut-Off Value.

BACKGROUND: The clinical practice shows that many low-dose ACTH-stimulation tests have a false positive result. The aim of the study was to determine the diagnostic accuracy of a low-dose ACTH-stimulation test in the diagnosis of adrenal insufficiency and to define its optimal cut-off. METHODS: We analyzed data from 103 patients undergoing 1 µg ACTH-stimulation test. Four patients had adrenal insufficiency (AI) upon follow up: Two primary, and two secondary AI. Cortisol serum levels were evaluated at time 0, 20', and 30' after the injection of 1 µg i.v. of ACTH. The sensitivity, specificity, accuracy, and positive and negative predictive values of the test were calculated for both 20' and 30' sampling. The receiver operating characteristic (ROC) curve was obtained to assess the sensitivity and specificity of low-dose ACTH-stimulation test in the diagnosis of adrenal insufficiency at different cut-off values. RESULTS: Considering 500 nmol/L as the standard cut-off value, low-dose ACTH stimulation test showed a 100% sensitivity and a 67.3% specificity, with a high rate of false positive results. ROC curve analysis showed that the cut-off of 401.5 nmol/L is the best compromise between sensitivity (100%) and specificity (93.9%). CONCLUSIONS: By using a cut-off value of 401.5 nmol/L for the low-dose ACTH stimulation test, the number of false positive patients decreased significantly, but the sensitivity remained high.

Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications.

The age-related decline of serum T occurs in ~20-30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.

Substance Abuse and Male Hypogonadism.

Progressive deterioration of male reproductive function is occurring in Western countries. Environmental factors and unhealthy lifestyles have been implicated in the decline of testosterone levels and sperm production observed in the last fifty years. Among unhealthy lifestyles, substance and drug abuse is a recognized cause of possible alterations of steroidogenesis and spermatogenesis. Alcohol, opioids and anabolic-androgenic steroids are capable to reduce testosterone production in male interfering with testicular and/or hypothalamic-pituitary function. Other substances such as nicotine, cannabis, and amphetamines alter spermatogenesis inducing oxidative stress and subsequent apoptosis in testicular tissue. Substance and drug abuse is a potentially reversible cause of hypogonadism, defined as the failure of the testis to produce physiological concentrations of testosterone and/or a normal number of spermatozoa. The identification of the abuse is important because the withdrawal of substance intake can reverse the clinical syndrome. This review summarizes the most important clinical and experimental evidence on the effect of substance abuse on testosterone and sperm production.

Effects of Varicocele Treatment on Sperm Conventional Parameters: Surgical Varicocelectomy Versus Sclerotherapy.

INTRODUCTION: Varicocele is often associated with impaired sperm parameters. Different procedures have been developed for varicocele treatment. The aim of this study was to evaluate the effects of varicocele treatment on conventional sperm parameters. MATERIALS AND METHODS: We compared two different techniques of intervention: surgical varicocelectomy and sclerotherapy. We also evaluated the number of varicocele recurrences and the pregnancy rate. We included 102 patients (mean age 29.8 ± 0.8 years) with ultrasound diagnosis of varicocele. We excluded patients whose ultrasound evaluation and/or sperm parameters were not known before and after varicocele correction. We divided the patients (excluding 8 with azoospermia) into two subgroups: surgical varicocelectomy (n = 44) and sclerotherapy (n = 50). For each patient, we compared conventional sperm parameters before and after varicocele correction. RESULTS: After varicocele correction, we found a significant improvement in sperm concentration, total count and total motility. Considering the two subgroups, baseline sperm parameters did not differ significantly. Sperm concentration and total count increased significantly after varicocele correction by varicocelectomy. Varicocele correction by sclerotherapy resulted in a significant increase in sperm concentration, progressive and total motility. We found varicocele recurrence in 32% of patients who underwent varicocelectomy and in 19.7% of patients undergoing sclerotherapy. The pregnancy rate was higher after sclerotherapy (28%) than after surgical varicocelectomy (13%). CONCLUSION: Varicocele treatment must be recommended when other causes of infertility have been treated. Our results suggest the use of sclerotherapy for varicocele repair. LEVEL OF EVIDENCE: 2 b.

How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin.

Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes. Although many authors have studied how supplementation therapy may affect this important parameter for both in vivo and in vitro models, data are not yet robust enough to support firm conclusions. Regarding this last point, in this review our objective has been to evaluate the state of the art regarding supplementation with melatonin and myo-inositol in order to improve oocyte quality during ART. On the one hand, the antioxidant effect of melatonin is well known as being useful during ovulation and oocyte incubation, two occasions with a high level of oxidative stress. On the other hand, myo-inositol is important in cellular structure and in cellular signaling pathways. Our analysis suggests that the use of these two molecules may significantly improve the quality of oocytes and the quality of embryos: melatonin seems to raise the fertilization rate, and myo-inositol improves the pregnancy rate, although all published studies do not fully agree with these conclusions. However, previous studies have demonstrated that cotreatment improves these results compared with melatonin alone or myo-inositol alone. We recommend that further studies be performed in order to confirm these positive outcomes in routine ART treatment.

Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols.

Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) have demonstrated a lot of important effects in the regulation of glucose and lipid metabolism and in the correct functioning of adipose tissue. Recently, many studies have evaluated a possible effect of PPARs on tumor cells. The purpose of this review is to describe the effects of PPARs, their action and their future prospective; METHODS: Narrative review aimed to synthesize cutting-edge evidence retrieved from searches of computerized databases; RESULTS: PPARs play a key role in metabolic diseases, which include several cardiovascular diseases, insulin resistance, type 2 diabetes, metabolic syndrome, impaired immunity and the increasing risk of cancer; in particular, PPARα and PPARß/δ mainly enable energy combustion, while PPARγ contributes to energy storage by enhancing adipogenesis; CONCLUSION: PPAR agonists could represent interesting types of molecules that can treat not only metabolic diseases, but also inflammation and cancer. Additional research is needed for the identification of high-affinity, high-specificity agonists for the treatment of obesity, type 2 diabetes (T2DM) and other metabolic diseases. Further studies are needed also to elucidate the role of PPARs in cancer.

Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions.

The prevalence of obesity and metabolic diseases (such as type 2 diabetes mellitus, dyslipidaemia, and cardiovascular diseases) has increased in the last decade, in both industrialized and developing countries. This also coincided with our observation of a similar increase in the prevalence of cancers. The aetiology of these diseases is very complex and involves genetic, nutritional, and environmental factors. Much evidence indicates the central role undertaken by peroxisome proliferator-activated receptors (PPARs) in the development of these disorders. Due to the fact that their ligands could become crucial in future target-therapies, PPARs have therefore become the focal point of much research. Based on this evidence, this narrative review was written with the purpose of outlining the effects of PPARs, their actions, and their prospective uses in metabolic diseases and cancers.