Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women.
Ontology highlight
ABSTRACT: Myo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with ?-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect.PCOS patients, according to the Rotterdam ESHRE-ASRM criteria, with anovulation and infertility >?1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resistant PCOS patients. This treatment involved 2 g MI, taken twice per day by oral route, for three months. The Homeostasis Model Assessment (HOMA) index and MI plasma levels were measured. In the main phase, previously selected MI-resistant patients received the same daily amount of MI plus 50 mg ?-LA twice a day, for a further three months. Ovulation was assessed using ultrasound examination on days 12, 14 and 20 of the cycle. The HOMA index, lipid, hormone and MI plasma levels were detected at baseline and at the end of this phase.Thirty-seven anovulatory PCOS subjects were included in the study. Following MI treatment, 23 of the 37 women (62%) ovulated, while 14 (38%) were resistant and did not ovulate. In the latter group, MI plasma levels did not increase. These MI-resistant patients underwent treatment in the main phase of the study, receiving MI and ?-LA. After this combined treatment, 12 (86%) of them ovulated. Their MI plasma levels were found to be significantly higher than at baseline; also, a hormone and lipid profile improvement was recorded.The combination of MI with ?-LA allowed us to obtain significant progress in the treatment of PCOS MI-resistant patients. Therefore, this new formulation was able to re-establish ovulation, greatly increasing the chances of desired pregnancy.Clinical trial registration number: NCT03422289 ( ClinicalTrials.gov registry).
<h4>Background</h4>Myo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with α-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect.<h4>Methods</h4>PCOS patients, according to the Rotterdam ESHRE-ASRM criteria, with anovulation and infertility > 1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resi ...[more]
Project description:Syntheses of a metabolite of the second messenger myo-inositol 1,4,5-trisphosphate, myo-inositol 1,4-bisphosphate, and an analogue, the 1,4-bisphosphorothioate, are reported, by using phosphite chemistry on (+/-)-1,2:4,5-di-isopropylidene-myo-inositol. The synthesis of (+/-)-1,2:4,5-di-isopropylidene 3,6-bis[di-(2-cyanoethyl)]phosphite provides an intermediate that can be oxidized to either the corresponding bisphosphate or bisphosphorothioate. myo-Inositol phosphorothioates are proposed as novel analogues of myo-inositol phosphates; their resistance to phosphatase-catalysed breakdown is reported.
Project description:Antibiotic-resistant mechanisms are associated with fitness costs. However, why antibiotic-resistant bacteria usually show increasing adaptation to hosts is largely unknown, especially from the host's perspective. The present study reveals the host's varied response to balofloxacin-resistant Escherichia coli (BLFX-R) using an integrated proteome and metabolome approach and identifies myo-inositol and phagocytosis-related proteins as crucial biomarkers. Originally, macrophages have an optimal attractive preference to BLFX-S due to more polarization of BLFX-S than BLFX-R, which renders faster elimination to BLFX-S than BLFX-R. The slower elimination to BLFX-R may be reversed by exogenous myo-inositol. Primarily, myo-inositol depolarizes macrophages, elevating adherence to both BLFX-S and BLFX-R. Since the altered adherence is equal to both strains, the myo-inositol-treated macrophages are free of the barrier to BLFX-R and thereby promote phagocytosis of BLFX-R. This work provides a novel strategy based on metabolic modulation for eliminating antibiotic-resistant bacteria with a high degree of host adaptation.
Project description:The dimannosylatedinositol pseudotrisaccharide phospholipid of the lipoarabinomannan (LAM) component of the mycobacterial cell wall has attracted interest as a therapeutic target because of its uniqueness to mycobacteria, its assembly at an early stage in LAM biosynthesis and the immunological activity of oligosaccharides containing this subunit. Accordingly, analogues of this pseudotrisaccharide, α-d-mannose-(1 → 2)-α-d-mannose-(1 → 6)-d-myo-inositol are of interest as mechanistic probes and drug leads. C-glycosides are of special interest because of their hydrolytic stability and conformational differences compared to O-glycosides. Herein, as a prelude to C-glycoside analogues of this pseudotrisaccharide, we describe the synthesis of the C-glycoside of α-d-mannose-(1 → 6)-d-myo-inositol. The synthetic strategy centers on the elaboration of a C1-linked glycal-inositol, the glycone segment of which is assembled via an oxocarbenium ion cyclization on a thioacetal-enol ether precursor that originates from "glycone" and "aglycone" components.
Project description:Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome. Methods and Results. A total of 60 women were enrolled and randomly assigned (n = 30 per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose (96 ± 7 versus 108 ± 10 mg/dL), triglycerides (145 ± 14 versus 165 ± 18 mg/dL), visfatin (2.8 ± 0.8 versus 3.7 ± 1.1 ng/mL), resistin (27 ± 7 versus 32 ± 8 µg/L), and b-ALP (19 ± 7 versus 15 ± 5 µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months. Conclusions. The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered with NCT01400724.
Project description:AIM:To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate p?-cateninS552 as a biomarker of recurrent dysplasia. METHODS:We examined the effects of dietary myo-inositol treatment on inflammation, p?-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear p?-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS:In mice, p?-cateninS552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, p?-cateninS552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION:Enumerating crypts with increased numbers of p?-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
Project description:Cadmium (Cd) damages the thyroid gland. We evaluated the effects of myo-inositol (MI), seleno-L-methionine (Se) or their combination on the thyroids of mice simultaneously administered with Cd chloride (CdCl2). Eighty-four male mice were divided into 12 groups (seven mice each). Six groups (controls) were treated with 0.9% NaCl (vehicle), Se (0.2 mg/kg/day), Se (0.4 mg/kg/day), MI (360 mg/kg/day), MI+Se (0.2 mg/kg) and MI+Se (0.4 mg/kg). The other six groups were treated with CdCl2 (2 mg/kg), CdCl2+MI, CdCl2+Se (0.2 mg/kg), CdCl2+Se (0.4 mg/kg), CdCl2+MI+Se (0.2 mg/kg) and CdCl2+MI+Se (0.4 mg/kg). An additional group of CdCl2-challenged animals (n= 7) was treated with resveratrol (20 mg/kg), an effective and potent antioxidant. All treatments lasted 14 days. After sacrifice, the thyroids were evaluated histologically and immunohistochemically. CdCl2 reduced the follicular area, increased the epithelial height, stroma, and cells expressing monocyte chemoattractant protein-1 (MCP-1) and C-X-C motif chemokine 10 (CXCL10). CdCl2+Se at 0.2/0.4 mg/kg insignificantly reversed the follicular and stromal structure, and significantly decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI significantly reversed the thyroid structure and further decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI+Se, at both doses, brought all indices to those of CdCl2-untreated mice. MI, particularly in association with Se, defends mice from Cd-induced damage. The efficacy of this combination was greater than that of resveratrol, at least when using the follicular structure as a read-out for a comparison. We suggest that the use of these nutraceuticals, more specifically the combination of MI plus SE, can protect the thyroid of Cd-exposed subjects.
Project description:During cryopreservation, sperm undergoes structural and molecular changes such as ice crystal formation, DNA fragmentation, and reactive oxygen species (ROS) production, leading to decreased sperm quality after thawing. Antioxidants play a crucial role in preventing these damages, both in vivo and in vitro. One potent antioxidant is myo-inositol, known for its protective effects on sperm against ROS. This study aimed to investigate the protective effect of myo-inositol on cryopreserved boar semen. The semen was diluted, cooled, and cryopreserved using a BF5 extender. It was then divided into five groups: control and different concentrations of myo-inositol (0.5, 1, 1.5, and 2 mg/mL). The post-thaw evaluation included assessments of motility, viability, acrosome integrity, mitochondrial membrane potential (MMP), caspase activity, gene expression, ROS levels, apoptosis, and IVF with treated semen. Results showed that myo-inositol at 0.5 mg/mL improved motility, acrosome integrity, and fertilization ability. It also reduced the expression of pro-apoptotic genes and increased SMCP expression. Lower concentrations also demonstrated improved viability and reduced apoptosis and ROS levels. In conclusion, myo-inositol treatment during cryopreservation improved sperm quality, reduced apoptosis and ROS levels, and enhanced fertility rates in boar semen.
Project description:The enzyme myo-inositol oxygenase is the key enzyme of a pathway leading from myo-inositol to UDP-glucuronic acid. In Arabidopsis, myo-inositol oxygenase is encoded by four genes. All genes are strongly expressed in syncytia induced by the beet cyst nematode Heterodera schachtii in Arabidopsis roots. Here, we studied the effect of a quadruple myo-inositol oxygenase mutant on nematode development. We performed metabolite profiling of syncytia induced in roots of the myo-inositol oxygenase quadruple mutant. The role of galactinol in syncytia was studied using Arabidopsis lines with elevated galactinol levels and by supplying galactinol to wild-type seedlings. The quadruple myo-inositol oxygenase mutant showed a significant reduction in susceptibility to H. schachtii, and syncytia had elevated myo-inositol and galactinol levels and an elevated expression level of the antimicrobial thionin gene Thi2.1. This reduction in susceptibility could also be achieved by exogenous application of galactinol to wild-type seedlings. The primary function of myo-inositol oxygenase for syncytium development is probably not the production of UDP-glucuronic acid as a precursor for cell wall polysaccharides, but the reduction of myo-inositol levels and thereby a reduction in the galactinol level to avoid the induction of defence-related genes.
