d-Pinitol Improves Diabetic Sarcopenia by Regulation of the Gut Microbiome, Metabolome, and Proteome in STZ-Induced SAMP8 Mice.

d-Pinitol (DP) is primarily found in Vigna sinensis, which has been shown to have hypoglycemic and protective effects on target organs. However, the mechanism of DP in treating diabetic sarcopenia (DS) is still unclear. To explore the underlying mechanism of DS and the protective targets of DP by high-throughput analysis of 16S rRNA gene, metabolome, and the proteome. Streptozotocin-induced SAMP8 mice were intragastrically administrated DP (150 mg/kg) for 8 weeks. Fecal 16S rRNA gene sequencing and gastrocnemius muscle metabolomic and proteomic analyses were completed to investigate the gut-muscle axis interactions. DP significantly alleviated the muscle atrophy in diabetic mice. Dysfunction of the gut microbiota was observed in the DS mice. DP significantly reduced the Parabacteroides, Akkermansia, and Enterobacteriaceae, while it increased Lachnospiraceae_NK4A136. Metabolome and proteome revealed that 261 metabolites and 626 proteins were significantly changed in the gastrocnemius muscle of diabetic mice. Among these, DP treatment restored 44 metabolites and 17 proteins to normal levels. Functional signaling pathways of DP-treated diabetic mice included nucleotide metabolism, ß-alanine, histidine metabolism, ABC transporters, and the calcium signaling pathway. We systematically explored the molecular mechanism of DS and the protective effect of DP, providing new insights that may advance the treatment of sarcopenia.

Association of embryonic inositol status with susceptibility to neural tube defects, metabolite profile, and maternal inositol intake.

Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.

Effects of imidacloprid combined with validamycin on the population fitness and symbiotic of Nilaparvata lugens (Hemiptera: Delphacidae).

Using a high-efficiency insecticide in combination with fungicides that have different mechanisms of action is a conventional method in the current management of brown planthopper (BPH) resistance. In this study, we investigate the separate and combined effects of the low-toxicity fungicide validamycin and the non-cross-resistant insecticide imidacloprid on the fitness and symbiosis of BPH. These research results indicate that when the proportion of active ingredients in validamycin is combined with imidacloprid at a ratio of 1:30, the toxicity ratio and co-toxicity coefficient are 1.34 and 691.73, respectively, suggesting that the combination has a synergistic effect on the control of BPH. The number of yeast-like symbiotic (YLS) and dominant symbiotic (Noda) in the imidacloprid + validamycin groups were significantly lower than the other three treatment groups (validamycin, imidacloprid, and water). The results of the study on population fitness show that the lifespan of the BPH population in validamycin, imidacloprid, and imidacloprid + validamycin was shortened. Notably, the BPH populations in the imidacloprid + validamycin groups were significantly lower than other groups in terms of average generation cycle, intrinsic growth rate, net reproduction rate, finite rate of increase, and fitness. The Real-time quantitative PCR showed that validamycin and imidacloprid + validamycin can significantly inhibit the expression of the farnesyl diphosphate farnesyl transferase gene (EC2.5.1.21) and uricase gene (EC1.7.3.3), with imidacloprid + validamycin demonstrating the most pronounced inhibitory effect. Our research results can provide insights and approaches for delaying resistance and integrated management of BPH.

Myo-inositol rescued insulin resistance and dyslipidemia in db/db mice.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic ß cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

A novel mechanism of major ginsenosides from Panax ginseng against multiple organ aging in middle-aged mice: Phosphatidylcholine-myo-inositol metabolism based on metabolomic analysis.

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.

Actinidia arguta Extract Containing Myo-Inositol Suppresses TNF-α-Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3ß and NF-κB Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.

The regulation of MFG-E8 on the mitophagy in diabetic sarcopenia via the HSPA1L-Parkin pathway and the effect of D-pinitol.

BACKGROUND: Diabetic sarcopenia is a disease-related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG-E8 affects mitophagy and the protective role of D-pinitol (DP) in diabetic sarcopenia. METHODS: In vivo, streptozotocin-induced diabetic SAM-R1 (STZ-R1) and SAM-P8 (STZ-P8) mice (16-week-old) were used, and STZ-P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D-galactose (DG) induced senescent C2C12 models were established and received DP, MFG-E8 plasmid (Mover)/siRNA (MsiRNA), or 3-MA/Torin-1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co-immunoprecipitation (CO-IP) were used for hunting the interacted proteins of MFG-E8. RESULTS: In vivo, sarcopenia, mitophagy deficiency, and up-regulated MFG-E8 were confirmed in the STZ-P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ-P8 vs. STZ-P8; all P < 0.01), such as increased lean mass (8.47 ± 0.81 g vs. 7.08 ± 1.64 g), grip strength (208.62 ± 39.45 g vs. 160.87 ± 26.95 g), rotarod tests (109.7 ± 11.81 s vs. 59.3 ± 20.97 s), muscle cross-sectional area (CSA) (1912.17 ± 535.61 µm2 vs. 1557.19 ± 588.38 µm2), autophagosomes (0.07 ± 0.02 per µm2 vs. 0.02 ± 0.01 per µm2), and cytolysosome (0.07 ± 0.03 per µm2 vs. 0.03 ± 0.01 per µm2). DP down-regulated MFG-E8 in both serum (DP + STZ-P8: 253.19 ± 34.75 pg/mL vs. STZ-P8: 404.69 ± 78.97 pg/mL; P < 0.001) and gastrocnemius muscle (WB assay. DP + STZ-P8: 0.39 ± 0.04 vs. STZ-P8: 0.55 ± 0.08; P < 0.01). DP also up-regulated PINK1, Parkin and LC3B-II/I ratio, and down-regulated P62 in gastrocnemius muscles (all P < 0.01). In vitro, mitophagy deficiency and MFG-E8 up-regulation were confirmed in diabetic and senescent models (all P < 0.05). DP and MsiRNA down-regulated MFG-E8 and P62, and up-regulated PINK1, Parkin and LC3B-II/I ratio to promote mitophagy as Torin-1 does (all P < 0.05). HSPA1L was confirmed as an interacted protein of MFG-E8 in IP and CO-IP assay. Mover down-regulated the expression of Parkin via the HSPA1L-Parkin pathway, leading to mitophagy inhibition. MsiRNA up-regulated the expression of PINK1 via SGK1, FOXO1, and STAT3 phosphorylation pathways, leading to mitophagy stimulation. CONCLUSIONS: MFG-E8 is a crucial target protein of DP and plays a distinct role in mitophagy regulation. DP down-regulates the expression of MFG-E8, reduces mitophagy deficiency, and alleviates the symptoms of diabetic sarcopenia, which could be considered a novel therapeutic strategy for diabetic sarcopenia.

Enhancing chlamydospore production in Duddingtonia flagrans on solid substrate: The impact of mannitol and varied cultivation conditions.

Duddingtonia flagrans is a nematophagous fungus which has shown promising results as a non-chemical parasitic control tool. The fungus disrupts the parasite's life cycle by trapping larvae in the environment through the networks generated from chlamydospores, thus preventing the reinfection of animals. One barrier to the development of a commercial product using this tool is the need to increase chlamydospore production in the laboratory for its administration to livestock. The purpose of this study was to evaluate the addition of mannitol to an enriched culture medium and the effect of adverse cultivation conditions on chlamydospore production. D. flagrans was cultivated on Petri dishes with corn agar for 4 weeks at 27 °C and 70% relative humidity (RH). Four groups were then formed, all with Sabouraud agar as a base, to which different growth inducers were added: GSA (glucose Sabouraud agar), GSA-MI (glucose Sabouraud agar + meso inositol), GSA-E (enriched glucose Sabouraud agar), and AE-M (enriched agar + mannitol). After 4 weeks, chlamydospores were recovered by washing the surface of each plate with distilled water and then quantified. The medium that yielded the highest amount of chlamydospores was subjected to different cultivation conditions: NC (normal conditions): 70% RH and 27 °C, AC (adverse conditions) 1: 20% RH and 40 °C, CA2: 60% RH and 27 °C, and CA3: 55% RH and 24 °C. It was determined that mannitol increases chlamydospore production (65x106 chlamydospores/plate), and when reducing humidity by 10% under cultivation conditions it resulted in an approximately 10% increase in chlamydospore production compared to the control group. These results suggest that the addition of polyols, as well as its cultivation under certain environmental conditions, can improve chlamydospore production on a laboratory scale.

Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin.

Ivermectin has broad-spectrum antiviral activities. Despite the failure in clinical application of COVID-19, it can serve as a lead compound for the development of more effective broad-spectrum antivirals, for which a better understanding of its antiviral mechanisms is essential. We thus searched for potential novel targets of ivermectin in host cells by label-free thermal proteomic profiling using Huh-7 cells. Inositol monophosphatase (IMPase) was found among the proteins with shifted thermal stability by ivermectin. Ivermectin could inhibit IMPase activity and reduce cellular myo-inositol and phosphatidylinositol-4-phosphate levels. On the other hand, inositol could impair the antiviral activity of ivermectin and lithium, an IMPase inhibitor with known antiviral activity. As phosphatidylinositol phosphate is crucial for the replication of many RNA viruses, inhibition of cellular myo-inositol biosynthesis may be an important antiviral mechanism of ivermectin. Hence, inhibition of IMPase could serve as a potential target for broad-spectrum antiviral development.

Inositol-Exchange Activity in Human Primordial Placenta.

Human placenta is an intensively growing tissue. Phosphatidylinositol (PI) and its derivatives are part of the signaling pathway in the regulation of trophoblast cell differentiation. There are two different enzymes that take part in the direct PI synthesis: phosphatidylinositol synthase (PIS) and inositol exchange enzyme (IE). The presence of PIS is known in the human placenta, but IE activity has not been documented before. In our study, we describe the physiological properties of the two enzymes in vitro. PIS and IE were studied in different Mn2+ and Mg2+ concentrations that enabled us to separate the individual enzyme activities. Enzyme activity was measured by incorporation of 3[H]inositol in human primordial placenta tissue or microsomes. Optimal PIS activity was achieved between 0.5 and 2.0 mM Mn2+ concentration, but higher concentrations inhibit enzyme activity. In the presence of Mg2+, the enzyme activity increases continuously up to a concentration of 100 mM. PIS was inhibited by nucleoside di- and tri-phosphates. PI production increases between 0.1 and 10 mM Mn2+ concentration. The incorporation of [3H]inositol into PI increased by 57% when adding stabile GTP analog. The described novel pathway of inositol synthesis may provide an additional therapeutic approach of inositol supplementation before and during pregnancy.

Effects of myo-inositol on growth and biomarkers of environmental stress and metabolic regulation in Pacific white shrimp (Litopenaeus vannamei) reared at low salinity.

This study explored the role of myo-inositol in alleviating the low salinity stress of White Shrimp (Litopenaeus vannamei). Juvenile shrimp (0.4 ± 0.02 g) in low salinity (salinity 3) water were fed diets with myo-inositol levels of 0, 272, 518, 1020 and 1950 mg/kg (crude protein is 36.82 %, crude lipid is 7.58 %), fed shrimp in seawater at a salinity of 25 were fed a 0 mg/kg myo-inositol diet as a control (Ctrl). The experiment was carried out in tanks (50 L) with satiety feeding, and the experiment lasted for 6 weeks. After sampling, the serum was used to measure immune function, the hepatopancreas homogenate was used to measure the antioxidant capacity and hepatopancreas damage state, the hepatopancreas was used for transcriptomics analysis, and the gills were used for qPCR to measure osmotic pressure regulation. The results showed that the final weight and survival of the shrimp in the 1020 mg/kg group increased significantly compared with those in the other low salinity groups, but the final weight and biomass increase were significantly lower than those in the Ctrl group. Dietary myo-inositol improved the antioxidant capacity of shrimp under low salinity. B-cell hyperplasia and hepatic duct damage were observed in the hepatopancreas in the 0 mg/kg group. The results of transcriptome analysis showed that myo-inositol could participate in the osmotic pressure regulation of shrimp by regulating carbohydrate metabolism, amino acid metabolism, lipid metabolism and other related genes. Myo-inositol significantly affected the expression of related genes in ion transporter and G protein-coupled receptor-mediated pathways. This study demonstrated that myo-inositol can not only act as an osmotic pressure effector and participate in the osmolar regulation of shrimp through the phosphatidylinositol signaling pathway mediated by G protein-coupled receptors but also relieve low salinity stress by mediating physiological pathways such as immunity, antioxidation, and metabolism in shrimp. The binomial regression analysis of biomass increases and survival showed that the appropriate amount of myo-inositol in the L. vannamei diet was 862.50-1275.00 mg/kg under low salinity.

Activated Inositol Phosphate, Substrate for Synthesis of Prostaglandylinositol Cyclic Phosphate (Cyclic PIP)-The Key for the Effectiveness of Inositol-Feeding.

The natural cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is biosynthesized from prostaglandin E (PGE) and activated inositol phosphate (n-Ins-P), which is synthesized by a particulate rat-liver-enzyme from GTP and a precursor named inositol phosphate (pr-Ins-P), whose 5-ring phosphodiester structure is essential for n-Ins-P synthesis. Aortic myocytes, preincubated with [3H] myo-inositol, synthesize after angiotensin II stimulation (30 s) [3H] pr-Ins-P (65% yield), which is converted to [3H] n-Ins-P and [3H] cyclic PIP. Acid-treated (1 min) [3H] pr-Ins-P co-elutes with inositol (1,4)-bisphosphate in high performance ion chromatography, indicating that pr-Ins-P is inositol (1:2-cyclic,4)-bisphosphate. Incubation of [3H]-GTP with unlabeled pr-Ins-P gave [3H]-guanosine-labeled n-Ins-P. Cyclic PIP synthase binds the inositol (1:2-cyclic)-phosphate part of n-Ins-P to PGE and releases the [3H]-labeled guanosine as [3H]-GDP. Thus, n-Ins-P is most likely guanosine diphospho-4-inositol (1:2-cyclic)-phosphate. Inositol feeding helps patients with metabolic conditions related to insulin resistance, but explanations for this finding are missing. Cyclic PIP appears to be the key for explaining the curative effect of inositol supplementation: (1) inositol is a molecular constituent of cyclic PIP; (2) cyclic PIP triggers many of insulin's actions intracellularly; and (3) the synthesis of cyclic PIP is decreased in diabetes as shown in rodents.

Deficiency of immunoglobulin IgSF6 enhances antibacterial effects by promoting endoplasmic reticulum stress and the inflammatory response in intestinal macrophages.

Immunoglobulin superfamily (IgSF) members are known for their role as glycoproteins expressed on the surface of immune cells, enabling protein-protein interactions to sense external signals during immune responses. However, the functions of immunoglobulins localized within subcellular compartments have been less explored. In this study, we identified an endoplasmic reticulum (ER)-localized immunoglobulin, IgSF member 6 (IgSF6), that regulates ER stress and the inflammatory response in intestinal macrophages. Igsf6 expression is sustained by microbiota and significantly upregulated upon bacterial infection. Mice lacking Igsf6 displayed resistance to Salmonella typhimurium challenge but increased susceptibility to dextran sulfate sodium-induced colitis. Mechanistically, deficiency of Igsf6 enhanced inositol-requiring enzyme 1α/-X-box binding protein 1 pathway, inflammatory response, and reactive oxygen species production leading to increased bactericidal activity of intestinal macrophages. Inhibition of reactive oxygen species or inositol-requiring enzyme 1α-X-box binding protein 1 pathway reduced the advantage of Igsf6 deficiency in bactericidal capacity. Together, our findings provide insight into the role of IgSF6 in intestinal macrophages that modulate the ER stress response and maintain intestinal homeostasis.

Effect of type and concentration of antioxidant on sperm motility, viability, and DNA integrity of climbing perch Anabas testudineus Bloch, 1792 (Pisces: Anabantidae) post-cryopreservation.

Sperm quality is preserved through the crucial involvement of antioxidants, which play a vital role in minimizing the occurrence of reactive oxygen species (ROS) during the cryopreservation process. The suitability of the type and concentration of antioxidants are species-dependent, and this study is crucial in order to improve the quality of the climbing perch sperm post-cryopreservation. Therefore, this study aimed to determine the best type and concentration of antioxidants for cryopreservation of climbing perch Anabas testudineus sperm. To achieve this, 6 types of antioxidants, namely, ascorbic acid, beta-carotene, glutathione, butylated hydroxytoluene (BHT), myo-inositol, and alpha-tocopherol, with inclusion of a control were tested in 3 replications at three concentration levels of 0 mg/L (control), 20 mg/L, 40 mg/L, and 60 mg/L. Sperm was diluted in a glucose-base extender at a ratio of 1:60 (sperm: glucose base), then 10 % DMSO and 5 % egg yolk was added before cryopreservation for two weeks. The results showed that the type and concentration of antioxidants had a significant effect on the motility and viability of cryopreserved climbing perch sperm (P < 0.05), where the best results for ascorbic acid, beta-carotene, glutathione, myo-inositol, and alpha-tocopherol were obtained at a concentration of 60 mg/L, while BHT was at a concentration of 20 mg/L. The best results for glutathione, myo-inositol, and alpha-tocopherol were significantly different from other treatments, while the best results for ascorbic acid and beta-carotene (60 mg/L) were not significantly different from the 40 mg/L concentration, while the best results for BHT were not significantly different from the control treatments. Therefore, the best concentration of glutathione, myo-inositol, and alpha-tocopherol was 60 mg/L, while for ascorbic acid and beta-carotene it was 40 mg/L, and BHT was not recommended. DNA integrity analysis indicated the absence of fragmentation in all samples, including fresh, control, and treated sperm. Based on practical and economic considerations, myo-inositol at 60 mg/L was recommended for cryopreservation of climbing perch A. testudineus sperm.

The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria.

SETTING: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). OBJECTIVES: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. PARTICIPANTS: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20-40. DESIGN: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. METHODS: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). RESULTS: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). LIMITATIONS: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. CONCLUSIONS: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed.

Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: now and the future.

INTRODUCTION: This Expert Opinion covers recent updates in the use of Inositol in polycystic ovary syndrome (PCOS) and type II diabetes and gives support to researchers and clinicians. AREAS COVERED: This article discusses the role of Myo-Inositol (MI) and D-Chiro-Inositol (DCI) in physiological function, the use of MI in PCOS, the risks of using DCI in reproductive conditions, the 40:1 combination of MI/DCI in PCOS. Furthermore, we discuss the issues of insulin resistance and how α-lactalbumin may increase the intestinal bioavailability of MI. The paper then transitions to talk about the use of inositols in diabetes, including type II diabetes, Gestational Diabetes Mellitus (GDM), and double diabetes. Literature searches were performed with the use of PubMed, Google Scholar, and Web of Science between July and October 2023. EXPERT OPINION: Inositol therapy has grown in the clinical field of PCOS, with it demonstrating an efficacy like that of metformin. The use of α-lactalbumin has further supported the use of MI, as issues with intestinal bioavailability have been largely overcome. In contrast, the effect of inositol treatment on the different PCOS phenotypes remains an outstanding question. The use of inositols in type II diabetes requires further study despite promising analogous data from GDM.

Antioxidant and Antidiabetic Potential of Ormocarpum cochinchinense (Lour.) Merr. Leaf: An Integrated In vitro and In silico Approach.

Diabetes is a prevalent metabolic disorder associated with various complications. Inhibition of α-glucosidase and α-amylase enzymes is an effective strategy for managing non-insulin-dependent diabetes mellitus. This study aimed to investigate the antioxidant and antidiabetic potential of Ormocarpum cochinchinense leaf through in vitro and in silico approaches. The methanol extract exhibited the highest phenolic and flavonoid content over solvent extracts aqueous, acetone, hexane, and chloroform, the same has been correlating with strong antioxidant activity. Furthermore, the methanol extract demonstrated significant inhibitory effects on α-amylase and α-glucosidase enzymes, indicating its potential as an antidiabetic agent. Molecular docking analysis identified compounds, including myo-inositol, with favorable binding energies comparable to the standard drug metformin. The selected compounds displayed strong binding affinity towards α-amylase and α-glucosidase enzymes. Structural dynamics analysis revealed that myo-inositol formed a more stable complex with the enzymes. These findings suggest that O. cochinchinense leaf possesses antioxidant and antidiabetic properties, making it a potential source for developing therapeutic agents.

Acute and sub-acute metabolic change in different brain regions induced by moderate blunt traumatic brain injury.

The objective of the study was to observe the effect of moderate closed-head injury on hippocampal, thalamic, and striatal tissue metabolism with time. Closed head injury is responsible for metabolic changes. These changes can be permanent or temporary, depending on the injury's impact. For the experiment, 20 rats were randomly divided into four groups, each containing five animals. Animals were subjected to injury using a modified Marmarou's weight drop device; hippocampal, thalamic, and striatal tissue samples were collected after 1 day, 3 days, and 7 days of injury. NMR spectra were acquired following sample processing. Changes in myo-inositol, creatine, glutamate, succinate, lactate, and N-acetyl aspartic acid in hippocampal tissues were observed at day 3 PI. The tyrosine level in the hippocampus was altered at day 7 PI. While thalamic and striatal tissue samples showed altered levels of branched-chain amino acids and myo-inositol at day 1PI. Taurine, gamma amino butyric acid (GABA), choline, and alpha keto-glutarate levels were found to be significantly altered in striatal tissues at days 1 and 3PI. Acetate and GABA levels were altered in the thalamus on day 1 PI. The choline level in the thalamus was found to alter at all-time points after injury. The alteration in these metabolites may be due to the alteration in their respective pathways. Neurotransmitter and energy metabolism pathways were found to be altered in all three brain regions after TBI. This study may help better understand the effect of injury on the metabolic balance of a specific brain region and recovery.

Investigating the effect of combined use of selenium and Myo-inositol supplements on thyroid function and autoimmune characteristics in thyroid disorders: a systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically review the effect of selenium and inositol combination on thyroid function, autoimmune characteristics in thyroid diseases. RESEARCH DESIGN AND METHODS: To identify eligible studies, a systematic search was conducted in the PubMed/MEDLINE, Science-Direct, CINHAL, EMBASE, SCOPUS, Psychinfo, Cochrane, ProQuest, and Web of Science were searched using the main concepts, and all English-written articles that were published between 2007 and 2022 and had an available full text were examined. RESULTS: The data analysis of this research revealed that after the simultaneous use of selenium and inositol supplements, the level of Triiodothyronine(T3) increased by 0.105 in patients with thyroid disorders although this increase was not significant (P-value: 0.228). The level of Thyroxine (T4) significantly increased by 0.06 (P-value: 0.04). Anti-Thyroid Peroxidase Antibody (TPOAb) titer decreased by 119.36%, which was not significant (P-value: 0.070). Finally, the level of Thyroid-stimulating hormone (TSH) decreased by 1.45%, which was a significant change (P-value: 0.001). CONCLUSION: It was observed that simultaneous use of selenium and inositol supplements did not change the T3 and TPOAb titer levels; however, it leads to a decrease in TSH and increase in T4 levels. Further studies are required due to the limited number of studies.

The Jinggangmycin-induced Mthl2 gene regulates the development and stress resistance in Nilaparvata lugens Stål (Hemiptera: Delphacidae).

Methuselah (Mth) belongs to the GPCR family B, which regulates various biological processes and stress responses. The previous transcriptome data showed jinggangmycin (JGM)-induced Mthl2 expression. However, its detailed functional role remained unclear in brown planthopper, Nilaparvata lugens Stål. In adult N. lugens, the Mthl2 gene showed dominant expressions, notably in ovaries and fat body tissues. The 3rd instar nymphs treated with JGM increased starvation, oxidative stress, and high temperature (34 °C) tolerance of the adults. On the contrary, under dsMthl2 treatment, completely opposite phenotypes were observed. The lipid synthesis genes (DGAT1and PNPLA3) of both females and males treated with JGM in the nymphal stage were observed with high expressions, while the lipolysis of the Lipase 3 gene was observed with low expressions. The JGM increased triglyceride (TG) content, fat body droplet size, and the number of fat body droplets. The same treatment also increased the Glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. An increase in the heat shock protein (HSP70 and HSP90) expression levels was also observed under JGM treatment but not dsMthl2. The current study demonstrated the influential role of the Mthl genes, particularly the Mthl2 gene, in modulating the growth and development and stress-responsiveness in N. lugens. Thus, providing a platform for future applied research programs controlling N. lugens population in rice fields.