Paradoxical sleep deprivation and restriction promote castration-like effects and local inflammatory responses in male gerbil prostate.

Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR - 96/96 h), and sleep restriction (SR - 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.

The anti-inflammatory properties of green tea extract protect against gentamicin-induced kidney injury.

We assessed in vivo the protective effects and underlying antioxidant and anti-inflammatory properties of dry green tee extract (GTE) on glomerular and tubular kidney function and structure in an experimental model of gentamicin (GEN)-induced nephrotoxicity. Wistar rats were divided into four groups and treated daily for 10 days. The control group received distilled water; the GTE group received 20 µg/g body weight (BW) GTE by gavage; the GEN group received 100 mg/g BW GEN intraperitoneally; and the GEN+GTE group received GTE and GEN simultaneously, as described above. At the beginning and end of treatment, the serum creatinine, fractional excretion of sodium and potassium, and plasma heme oxygenase (HO)-1 levels and oxidative stress (OS) were assessed. At the end of the experiment, kidney fragments were collected for histological evaluation and immunohistochemical studies of cyclooxygenase (COX)-2 and nuclear factor (NF)kB. The levels of interleukin (IL)-1b, IL-4, IL-6, IL-10 and monocyte chemotactic protein (MCP)-1 were measured in kidney tissue. The results showed that GTE attenuated significantly kidney structural injury and prevented GEN-induced kidney functional injury (glomerular and tubular function). GTE significantly attenuated the kidney tissue increase of the proinflammatory mediators NF-kB, COX2, IL-1b and MCP-1 and significantly increased the kidney expression of the anti-inflammatory cytokines IL-6 and IL-10. However, GTE did not prevent OS increase in GEN-treated animals. In conclusion, GTE protected against GEN nephrotoxicity, likely due to direct blockade of the inflammatory cascade, which might had occurred independently of its antioxidant effect.

Mimetic peptide AC2-26 of annexin A1 as a potential therapeutic agent to treat COPD.

Chronic obstructive pulmonary disease (COPD) is related to inflammatory process caused by smoking habit. In this scenario, the anti-inflammatory protein Annexin A1 (AnxA1) may represent a therapeutic alternative. We performed experiments to evaluate the effects of the AnxA1 mimetic peptide Ac2-26 in an initial COPD model by physiological, histopathological, biochemical and immunohistochemical analyses. Weight loss, increased blood pressure, reductions in the pulmonary frequency and ventilation, loss of tracheal cilia, enlargement of the pulmonary intra-alveolar spaces and lymphoid tissue found in untreated smoke-exposed group were attenuated by AnxA1 peptide treatment. The Ac2-26 administration also protected against leukocytes influx in bronchoalveolar lavage (BAL), lung and trachea, and it also led to decreased hemoglobin, glucose, cholesterol, gamma glutamyl transferase and aspartato aminotransferase levels. Similarly, reduction of proinflammatory mediators and higher concentration of anti-inflammatory cytokine were found in macerated lung supernatant, blood plasma and BAL in the treated animals. Besides Ac2-26 group showed reduced tissue expressions of AnxA1, cyclooxygenase-2 and metalloproteinase-9, but formylated peptide receptor 2 (FPR2) overexpression. Our results all together highlighted the protective role of the Ac2-26 mimetic peptide in COPD with promising perspectives.

Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy.

Depression and anxiety, the most important psychological disorders in cancer patients, have now been considered as psychoneuroimmunological disorders, in which peripheral immune activation, through the release of proinflammatory cytokines, is implicated in the variety of behavioral, neuroendocrine and neurochemical alterations associated with these disorders. Along with the tumor itself, cancer treatment can also contribute to exacerbate the production of proinflammatory cytokines. This study aimed to investigate whether proinflammatory cytokine levels are related to depression and anxiety in CRC patients in different stages of the antitumor therapy We evaluated 60 patients in three stages of antitumor therapy (Pre-chemotherapy, Under-chemotherapy and Post-chemotherapy, n=20 in each group) and 20 healthy volunteers by the Hospital Anxiety and Depression Scale (HADS). Serum levels of cytokines were measured by CBA. Depression and/or anxiety were found at clinically relevant levels in CRC patients during all antitumor therapy. Patients in pre-chemotherapy group exhibited the highest concentrations of pro-inflammatory cytokines and the lowest levels of IL-10. In latter stages of treatment, cytokines reached levels similar to the control group. Correlation analysis between HADS score and cytokine serum levels revealed positive associations of anxiety and/or depression with IL-1ß, IL-6, IL-8, and TNF-α, and a negative correlation with IL-10, suggesting that cytokines are involved in the pathophysiology of these psychological disorders in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of new therapeutic strategies to assist in alleviating such symptoms in cancer patients.