Endometriosis is a disorder characterised by presence and growth of endometrial tissue outside the uterus, primarily into the peritoneum. The peritoneal fluid (PF) of women with endometriosis undergoes a number of biological changes, including local inflammatory-reparative phenomena and peripheral blood mononuclear cells (PBMC) involvement. These activated cells as well as the endometriotic cells secrete various cytokines with pleiotropic biological activities. Dynamic interplay among cytokines may contribute to realise a favourable microenvironment for the implantation of endometrial cells and the progression of the disease. In the present study, we evaluated the levels of cytokines, such as the tumour necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in PF and in serum (S) of women with endometriosis to compare their behaviour in both biological fluids. The patients (n = 26) were women of reproductive age attending our observation centre for infertility, diagnosed endometriosis at laparoscopy. Control group (n = 5) consisted of women affected by non-immunologic infertility, diagnosed by explorative laparoscopy. S samples were obtained from peripheral blood before anaesthesia and laparoscopy. PF samples were collected at the time of laparoscopy. Both biological fluids were examined for cytokine by ELISA assays. Our results showed that S and PF levels of TNF-α, not dosable in controls, were very high at the early stage and decreased significantly with the severity of the disease (p < 0.001). TGF-β levels were significantly (p < 0.001) higher than in controls and increased with the severity of the disease (p < 0.001), particularly in the PF. S and PF IL-8 as well as MCP-1 concentrations at all stages were higher than in controls (p < 0.001), yet showed an opposite behaviour in both biological fluids. In fact, S levels of IL-8 and MCP-1 were significantly (p < 0.001) higher at early stages and decreased with the severity of the disease, whereas we observed a significant (p < 0.001) enhancement of these chemokine levels in PF from stage I to stage II and stage III. These observations showed that TNF-α and TGF-β levels were overlapping in S and PF of women with endometriosis. On the contrary, MCP-1 and IL-8 S concentrations decreased with the severity of the disease, whereas PF levels showed markedly increased at severe stages. Taken together the observed changes may be due both to the increased peritoneal macrophage activity and to the larger recruitment of PBMC and autocrine release by endometriotic cells.

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Considering the large amount of evidence retrieved from in vitro as well as in vivo models, the reduced apoptosis of endometriotic cells together with the increased apoptosis of peritoneal fluid mononuclear cells may address the peritoneal homeostasis to a permissive environment for the progression of the disease.

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 PPARβ/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.

Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, loss of synapses and neurons and chronic neuroinflammation. Emerging data highlight the involvement of innate immunity, that has been shown to play opposing roles during the AD progression. Activated microglia and reactive astrocytes exert neuroprotection mediated through Aβ phagocytosis in the early stage, whereas, as the disease progresses, they fail in Aβ clearance and exert detrimental effects, including neuroinflammation and neurodegeneration. Specific toll-like receptors (TLRs) and coreceptors can directly or indirectly be activated to induce Aβ uptake or inflammatory responses, depending on the disease stage. Fibrillar Aβ can directly interact with TLR2, TLR4, and CD14 to induce microglial Aβ phagocytosis in the beginning stages, and neuroinflammatory responses in the late stages. Early TLR3-mediated signal enhances neuronal Aβ autophagy, although it increases neuronal apoptosis in the late AD stage. Similarly, TLR7, TLR8 and TLR9 can enhance microglial Aβ uptake in the early stage, but over time they contribute to neuroinflammation. Therefore, TLRs, and in particular TLR2 and TLR4, represent a suitable target for therapeutic intervention within the disease progression and targeting them carefully could increase Aβ autophagy and phagocytosis or reduce inflammatory responses. Several modulators with selective TLR agonist or antagonist activity have been developed, and many of them could have a therapeutic benefit in AD patients. This paper outlines the role of specific TLRs in AD, also focusing on TLR-targeted compounds yet indicated for the treatment of other inflammatory diseases, that could be used to treat the different stages of the disease.