Several studies have shown the presence of components of the renin–angiotensin system in mammalian ovaries and their involvement in ovarian physiology. We have previously shown the presence of angiotensin‐(1–7) [Ang‐(1–7)], an important biologically active component of the renin–angiotensin system, and its receptor, Mas, in rat, rabbit and human ovaries. We have also shown the involvement of Ang‐(1–7) in the rabbit ovulatory process in vitro. In the present study, we observed that Ang‐(1–7) stimulated the resumption of meiosis in oocytes of rat preovulatory follicles, reaching more than 30% of oocytes with germinal vesicle breakdown. The specific antagonist of the Mas receptor, A‐779, inhibited the germinal vesicle breakdown induced by Ang‐(1–7) and reduced the oocyte maturation stimulated by luteinizing hormone (LH). Immunohistochemistry showed that LH increased both Ang‐(1–7) and angiotensin‐converting enzyme 2 (ACE2) staining in preovulatory follicles. The effect of gonadotrophins on mRNA expression of Mas and ACE2 in ovaries of immature equine chorionic gonadotrophin‐primed rats was analysed by real‐time PCR after 6 h of human chorionic gonadotrophin (hCG) injection, which exhibits LH‐like effects. After hCG treatment, ACE2 mRNA expression was higher in the ovaries of treated rats than in the ovaries of control rats, whereas Mas mRNA levels were unchanged. A‐779 changed the steroidogenesis stimulated by LH. An increased testosterone concentration and decreased progesterone levels were measured in the follicle medium. In conclusion, our results suggest that LH upregulates the ACE2–Ang‐(1–7)–Mas axis and that Ang‐(1–7) promotes meiotic resumption, possibly as a gonadotrophin intermediate.
Cancer is one of the leading causes of death worldwide. Although several drugs are used clinically, some tumors either do not respond or are resistant to the existing pharmacotherapy, thus justifying the search for new drugs. Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low solubility in aqueous medium, which presents a barrier to its biological applications. In this context, the use of liposomes presents a promising strategy to deliver UA and allow for its intravenous administration. In this work, long-circulating and pH-sensitive liposomes containing UA (SpHL-UA) were developed, and their chemical and physicochemical properties were evaluated. SpHL-UA presented adequate properties, including a mean diameter of 191.1 ± 6.4 nm, a zeta potential of 1.2 ± 1.4 mV, and a UA entrapment of 0.77 ± 0.01 mg/mL. Moreover, this formulation showed a good stability after having been stored for 2 months at 4°C. The viability studies on breast (MDA-MB-231) and prostate (LNCaP) cancer cell lines demonstrated that SpHL-UA treatment significantly inhibited cancer cell proliferation. Therefore, the results of the present work suggest the applicability of SpHL-UA as a new and promising anticancer formulation.
PURPOSE: The purpose of this study was to investigate the effect of polyhexamethylene biguanide (PHMB) solution as a wound cleanser on bacterial load and bacterial biofilm in venous leg ulcers. DESIGN: Randomized controlled trial. SUBJECTS AND SETTING: The target population was adults attending the dermatology outpatient clinic of the Clinical Hospital of the Federal University of Minas Gerais, Brazil. The sample comprised 44 patients with venous leg ulcers recruited over a 6-month period. METHODS: Participants were divided into 2 groups: the intervention group had their wounds cleansed with PHMB, and the control group had their wound cleansed with a 0.9% saline solution. Tissue fragments of the wounds were collected for bacteriological analysis; transmission electron microscopy was used to identify the presence of biofilm. RESULTS: The bacterial load was reduced in both groups compared to baseline values; no significant difference was found when groups were compared. Correlation analysis between wound duration (months), wound area (cm²), necrosis (%), variables, and bacterial count (colony forming units [CFUs]/g) after cleansing showed a significant relationship between area of the wound and CFUs/g (P = .0070, r = 0.51). Transmission electron microscopy revealed the presence of bacterial biofilm in the wounds after cleansing with both solutions. CONCLUSIONS: The results of this study indicate that both PHMB and saline solution are effective in reducing the bacterial load in venous leg ulcers. However, bacterial biofilm was present after cleansing with both solutions. These findings provide important evidence regarding effectiveness of 2 common wound cleansers on bacterial presence in wounds.
Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming without workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (without workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in Pgc1α expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming without workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis.