Solanum lycopersicum (Tomato)-Derived Nanovesicles Accelerate Wound Healing by Eliciting the Migration of Keratinocytes and Fibroblasts.

Plant-derived nanovesicles have been considered interesting in medicine for their breakthrough biological effects, including those relevant to wound healing. However, tomato-derived nanovesicles (TDNVs) have not been studied for their effects on wound closure yet. TDNVs were isolated from Solanum lycopersicum (var. Piccadilly) ripe tomatoes by ultracentrifugation. Extract (collected during the isolation procedure) and NVs (pellet) were characterized by transmission electron microscopy and laser Doppler electrophoresis. Wound healing in the presence of Extract or NVs was analyzed by a scratch assay with monocultures of human keratinocytes (HUKE) or NIH-3T3 mouse fibroblasts. Cell proliferation and migration were studied by MTT and agarose spot assay, respectively. The vesicles in the Extract and NV samples were nanosized with a similar mean diameter of 115 nm and 130 nm, respectively. Both Extract and NVs had already accelerated wound closure of injured HUKE and NIH-3T3 monocultures by 6 h post-injury. Although neither sample exerted a cytotoxic effect on HUKE and NIH-3T3 fibroblasts, they did not augment cell proliferation. NVs and the Extract increased cell migration of both cell types. NVs from tomatoes may accelerate wound healing by increasing keratinocyte and fibroblast migration. These results indicate the potential therapeutic usefulness of TDNVs in the treatment of chronic or hard-to-heal ulcers.

Vaginal colonization of women after oral administration of Lactobacillus crispatus strain NTCVAG04 from the human microbiota.

BACKGROUND: The genomic approach has deeply changed the microbiology perspective, mainly concerning the microbioma identification. In this regard, some microbes colonize the healthy vagina. Vaginitis is a common gynecological ailment and includes bacterial vaginosis (BV), usually caused by local dysbiosis, such as a microbiota imbalance. Lactobacilli are the most prevalent bacteria colonizing the healthy vagina, so guaranteeing local eubiosis. In particular, vaginal colonization by L. crispatus is associated with low susceptibility to BV. Therefore, probiotics, such as life bacteria providing health advantages, are a current strategy in the prevention or treatment of vaginitis, including BV. However, there is a low level of evidence that probiotics after ingestion could really colonize the vagina. In particular, no study evidenced that L. crispatus after ingestion can colonize vagina. Therefore, the current study explored the capacity of Biovaginil® (NTC, Milan, Italy) dietary supplement containing Lactobacillus crispatus NTCVAG04 and vitamin A to colonize the gut and vagina in women with a history of vaginitis/vaginosis. METHODS: Twenty fertile females (mean age 34.0 years) were enrolled in the study. Rectal and vaginal swabs were collected at baseline and after the first and second cycle of Biovaginil®. Each cycle lasted 14 days within two consecutive menstrual periods. RESULTS: Seven women were excluded from the analysis because the samples were technically not evaluable. One woman dropped out because of mild adverse event. At the end of the study, nine women (75%) had positive rectal swab for L. crispatus NTCVAG04, and 8 of them also had positive vaginal swab. CONCLUSIONS: The current study provided the first evidence that L. crispatus NTCVAG04, administered by two Biovaginil® courses, colonized both the gut and vagina. Moreover, the L. crispatus NTCVAG04 strain could be considered the archetype of a new class of oral probiotics that actively colonize the vagina, and that could be called "colpobiotics."

PCOS Physiopathology and Vitamin D Deficiency: Biological Insights and Perspectives for Treatment.

Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated with insulin resistance and increased diabetes risk. Since women with PCOS and hirsutism seem to have lower levels of VD than women with PCOS without hirsutism, a correlation between VD deficiency and hyperandrogenism may be suggested. Interestingly, VD is crucial for many human physiological functions, including to counteract inflammation and oxidative stress. Some studies evaluated effects of VD supplementation on glucose homeostasis variables, hormonal status, lipid concentrations, and biomarkers of inflammation and oxidative stress among VD-deficient women. Moreover, VD has been shown to play a role in egg quality and fertility. This review aims to show the relationship between VD and the endocrine and metabolic profile of PCOS patients, as well as its implications for their fertility. The supplement of VD to the common therapy can lead to an improvement of the insulin resistance and lipid metabolism, a reduction of circulating androgens, as well as a better response to the induction of ovulation in PCOS women.

Role of a natural integrator based on lipoic acid, palmitoiletanolamide and myrrh in the treatment of chronic pelvic pain and endometriosis.

BACKGROUND: Dysmenorrhea and chronic pelvic pain occur in a significantly higher percentage in women with endometriosis; this benign condition has an incidence ranging from 5% to 10% in the general population, while 35% to 50% of infertile women are affected. Treatment of the symptoms demands integrated approaches with the use of anti-inflammatory substances or drugs and lifestyle changes, including attention to diet. The use of traditional anti-inflammatory drugs over the long term is not very successful because of the fear of side effects so they are almost always used with a short-term formula of 7-10 days when the woman's general condition becomes difficult to bear. In recent years, particular attention has been paid to natural substances with recognized anti-inflammatory activities that, associated with one another, are able to synergize individual actions. A nutraceutical containing substances capable of fighting chronic pelvic pain has recently been put on the market. The possible action mechanism derives from a synergy of action between alpha-lipoic acid, palmitoiletanolamide (PEA) and myrrh (Pelvinox, Laborest Italia srl, Nerviano, Milan, Italy), whose action is so effective that it is able to replace the use of anti-inflammatory drugs. The aim of the study was to evaluate the effect of these active ingredients in women with endometriosis and chronic pelvic pain. METHODS: This multicenter study saw the recruitment of 60 women (divided between the three centers participating in the study, Siena, Bologna and Udine) aged between 20 and 39 suffering from endometriosis (ovarian) and chronic pelvic pain. All the women took one nutraceutical (Pelvinox) at a dose of two tablets per day for 6 months. RESULTS: The results showed a significant reduction in pain symptoms as regards dyspareunia, dysmenorrhea and chronic pelvic pain, while there was no change in the mean diameter of the endometriosis cysts. CONCLUSIONS: In light of the above, it is believed that substances such as alpha-lipoic acid, PEA and myrrh may play a very important role in this type of patient in the treatment of individual symptoms.

[Evaluation of the effects of a natural dietary supplement with cranberry, Noxamicina® and D-mannose in recurrent urinary infections in perimenopausal women].

BACKGROUND: The female genital apparatus, the urinary tract and the perineal supporting tissues share a common embryological origin, whose differentiation depends on the action of estrogens. In adult women, the progressive decline of the ovarian function, with the ensuing estrogen deprivation, reduces tissue tropism causing urogenital atrophy, which makes these organs much more susceptible to traumatisms and urinary infections. The disorders associated with changes in the urogenital tract of peri- and postmenopausal women have significant clinical relevance, both on account of their chronicity and high frequency of occurrence and on account of their having major repercussions on the quality of life of the women, who often have to call their doctor seeking relief for their symptoms. In general, these patients report having a significant number of episodes of cystitis per year. With a view to verifying whether the use of a new dietary supplement (Kistinox® Forte sachets) containing cranberry (Vaccinium macrocarpon), Noxamicina® (propolis extract) and D-mannose can be of use in the treatment of cystitis, with or without bacteriuria, through the elimination of urinary symptoms, a multicenter clinical study was conducted on 150 women aged 40 to 50 suffering from recurrent episodes of cystitis as attested by at least one positive urine culture during the six months preceding their recruitment. METHODS: The subjects were randomly assigned to two groups: Group A: 100 women were given Kistinox® Forte, 1 sachet per day during the first 10 days of the month, for 3 months; Group B: 50 women did not receive any treatment to serve as a control group. RESULTS: The results of the present study show a complete remission of urinary symptoms in 92 women; a slight decrease in urinary symptoms was observed in 5 subjects, whereas 3 women who stopped the treatment after the first cycle were considered drop-outs. CONCLUSIONS: This multicenter clinical study revealed the excellent efficacy and tolerability of Kistinox® Forte sachets in the treatment and prevention of urinary disorders in peri- and postmenopausal women. The posology of a sachet a day during the first 10 days of the month for 3 months was well tolerated by the patients, who did not report any disorder arising from the product.

Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF.

BACKGROUND: The status characterized by the imbalance between pro-oxidants and antioxidants molecules, defined as oxidative stress, has been suggested to be involved in the pathogenesis of subfertility in females. This study aims to evaluate the impact of a complete micronutrients supplementation on oxidative stress levels in follicular microenvironment as well as on in vitro fertilization (IVF) outcome. METHODS: This preliminary study was conducted between January 2014 and July 2015 at the Siena University Hospital Infertility Clinic. Serum and follicular fluid were collected from infertile women aged > 39 years who underwent two in vitro fertilization cycles: in the first cycle they were treated with GnRH-antagonist protocol and gonadotropins for controlled ovarian hyperstimulation, whereas in the second cycle ovarian stimulation protocol was associated to micronutrients supplementation, starting three months earlier. Protein oxidation levels and total antioxidant capacity in serum and in follicular fluid were evaluated in IVF cycles with or without micronutrients supplementation. Differences in IVF outcome parameters were statistically evaluated. RESULTS: Two-dimensional electrophoresis analyses demonstrated that when patients assumed micronutrients before IVF cycles, follicular fluid and serum proteins were protected from oxidative damage. Comparable results were obtained when total antioxidant capacity was measured. Moreover, the mean number of good quality oocytes retrieved when patients received micronutrients supplementation was significantly increased. CONCLUSION: The additional treatment with micronutrients, starting three months before IVF cycles, protects the follicular microenvironment from oxidative stress, thus increasing the number of good quality oocytes recovered at the pick up.

Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women.

The aim of this study was to evaluate the efficacy of a food supplement combination based on isoflavones and berberine (ISB) in the treatment of menopausal symptoms and dyslipidaemia. Isoflavones are extracted from soy and absorbed in the body after being activated by lactobacillus. Berberine, extracted from the plant Berberis aristata, lowers plasma cholesterol and triglycerides (TG) by increasing low-density lipoprotein (LDL) receptors and reducing hepatic synthesis of TG. One hundred twenty women with a mean age of 54.8 ± 0.6 years were enrolled and randomized to treatment with ISB (estromineral lipid [EL] = 60 cases) or calcium and vitamin D(3) (CaD = 60 cases). Menopausal symptoms, plasma cholesterol, and TG were evaluated at baseline, and after 4 and 12 weeks. EL treatment significantly lowered plasma total cholesterol (-13.5% ± 0.7 vs -0.2% ± 0.5), LDL cholesterol (-12.4% ± 1.5 vs + 0.8 % ± 0.7) and TG (-18.9% ± 2.5 vs -1.3% ± 1.2) and improved menopausal symptoms compared with CaD treatment. Safety parameters were unchanged during the study. The combination of berberine and isoflavones was effective in lowering cardiovascular (CV) risk factors in menopausal women with moderate dyslipidaemia and in improving their quality of life.

The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen.

In an attempt to evaluate the role of inositol supplementation in insulin-resistant patients with polycystic ovary syndrome (PCOS), undergoing gonadotropin ovulation induction using the low-dose step-down regimen, we conducted a prospective longitudinal study comparing the stimulation characteristics of 15 patients treated with inositol, to a cohort, matched by age and body mass index (BMI), without inositol. Inositol nutritional supplementation produced very good clinical results with a significant reduction in cancellation rate (0 vs. 40%) and the consequent improvement in clinical pregnancy rate (PR) (33.3% vs. 13.3%).

Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia.

AIM: To study the immune-modulating and anti-oxidant effects of beta-glucan, papaya, lactoferrin, and vitamins C and E on sperm characteristics of patients with asthenoteratozoospermia associated with leucocytosis. METHODS: Fifty-one patients referred to our Sterility Center for semen analysis were selected. Sperm parameters were assessed before and after patient's treatment with beta-glucan, lactoferrin, papaya, and vitamins C and E. DNA damage was assessed by the acridine orange test and sperm structural characteristics were evaluated by transmission electron microscopy. RESULTS: After 90 days of treatment, an increase in the percentage of morphologically normal sperm (17.0 +/- 5.2 vs. 29.8 +/- 6.5) and total progressive motility (19.0 +/- 7.8 vs. 34.8 +/- 6.8) were detected. Structural sperm characteristics as well as chromatin integrity were also improved after treatment. In terms of leukocyte concentration in seminal fluid, a significant reduction was recorded (2.2 +/- 0.9 vs. 0.9 +/- 0.2). CONCLUSION: The treatment of an inflammatory process by the synergic action of immune modulators and anti-oxidants could protect sperm during maturation and migration, leading to improved sperm function.

Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality.

BACKGROUND: The objective of the study was to investigate the hypothalamo-pituitary-testicular axis and sperm structure at the transmission electron microscope (TEM) level in men affected by insulin-dependent diabetes. METHODS: Twenty-two diabetic men and 24 controls were recruited. GnRH (100 micro g) was administered and FSH- and LH-induced secretion was evaluated. Semen samples were collected and sperm concentration and motility were determined using a Makler chamber. Ejaculated sperm were fixed and observed with a TEM. RESULTS: The response of gonadotrophins to GnRH was significantly lower in diabetics than in control men. Sperm motility was also significantly lower. At the electron microscope level, sperm from diabetics exhibited a higher percentage of immaturity- and apoptosis-related defects than sperm from controls. CONCLUSIONS: The reduced response of gonadotrophins to GnRH in diabetic men may indicate a decreased acute releasable pool of pituitary gonadotrophins. The results of TEM examination showed that sperm from men with diabetes presented severe structural defects in comparison with sperm from controls. It is possible that the reproductive impairment recognized in men with diabetes could be the result of interference by the disease on the hypothalamo-pituitary-testicular axis at multiple levels, as indicated by the reduced gonadotrophin response to appropriate stimuli and by the abnormal ultrastructure of ejaculated sperm. The defective spermatogenesis may be the consequence of a direct testicular effect of the disease.