Inositol Research Articles

Hippocampal region metabolites and cognitive impairment in patients with general paresis: based on 1H-proton magnetic resonance spectroscopy.

This study utilizes Hydrogen proton magnetic resonance spectroscopy (1H-MRS) to investigate metabolite concentrations in the bilateral hippocampus of general paresis (GP) patients. A total of 80GP patients and 57 normal controls (NCs) were enrolled. Metabolite ratios in the bilateral hippocampus were measured using 1H-MRS. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on MMSE scores, participants were categorized into normal control, mild cognitive impairment, and moderate-severe dementia groups. Metabolite ratios (N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/choline (Cho), myoinositol (MI)/creatine (Cr), choline (Cho)/N-acetylaspartate (NAA)) were compared between groups, and correlations between metabolite ratios and cognitive performance were examined. MMSE scores progressively decreased in the normal, mild cognitive impairment, and moderate-severe dementia groups (p < 0.001). The moderate-severe dementia group showed significantly lower NAA/Cr ratios in the left hippocampus region (L-NAA/Cr ratios) (p < 0.001) and higher Cho/NAA ratios in the left hippocampus region (L-Cho/NAA ratios) (p < 0.05) compared to the other groups. However, differences in L-NAA/Cr and L-Cho/NAA ratios between the mild cognitive impairment group and the NC group were not significant in the hippocampus region (p > 0.05). NAA/Cho and NAA/Cr ratios in the right hippocampus region (R-NAA/Cho and R-NAA/Cr ratios) in the moderate-severe dementia group were lower than those in the control group (p < 0.05). No correlation was found between metabolite ratios and MMSE scores in bilateral hippocampus regions. There are distinctive metabolic characteristics in the hippocampus of GP patients. GP patients exhibited lower NAA/Cr and NAA/Cho ratios in the bilateral hippocampus, indicating neuron loss in these areas, which may become more pronounced as the disease progresses.

Proton Magnetic Spectroscopy in Diabetic Brain: A Comprehensive Review

Diabetes Mellitus (DM) is on the rise making it a major concern for global health. DM can be classified into type 1 or type 2, and both can lead to changes in brain metabolites. These can result in serious complications like cognitive decline, particularly if not managed properly by diabetic patients. Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that allows us to study the brain metabolite levels. The present review utilises available Magnetic Resonance Imaging (MRI) data to understand how brain metabolites are affected in both type 1 and type 2 diabetes (T2DM). Research shows that in individuals with diabetes, there are changes in important brain chemicals such as creatine (Cr), N-Acetyl Aspartate (NAA), Myo-Inositol (MI), choline (Cho), glutamate, and glutamine. A consistent finding across multiple studies showed a reduction in NAA levels, which is a key indicator of brain neuron health. This suggests that diabetes negatively impacts the function of neurons in the brain. Changes were seen in other metabolites indicating potential disruptions in energy regulation and membrane function. This review concludes that alterations in brain metabolites as measured using MRS, could serve as a non-invasive biomarker for tracking the progression of DM and its related complications

Inositol - why should it be in the spotlight for women in a reproductive age?

Introduction and purpose: Inositol exists in the form of nine isomers, two of which are dominant - myo-inositol (MI) and D-chiro-inositol (DCI). It is a naturally occuring sugar involved in many biological pathways. Due to its insulin-sensitizing, anti-inflammatory and antioxidant properties, inositol has been suggested as a novel treatment agent in prevention and treatment of reproductive disorders. The paper presents currently available data regarding the impact of oral supplementation of inositol for fertility of women and men, reproductive outcomes among subfertile women with polycystic ovarian syndrome (PCOS) and its effectiveness on preventing and treating gestational diabetes mellitus (GDM).&#x0D; Material and methods of research: The search was conducted using PubMed and Google Scholarship databases available to November 2023. &#x0D; Results: Although the evidence is still insufficient, it is suggested that inositol may be beneficial for subfertile women, also those undergoing assisted reproductive techniques and in vitro fertilization. Moreover inositol can positively influence sperm quality. Myoinositol supplementation was also effective and safe for pregnant women with GDM and their children. In these women lower HOMA-IR (Homeostatic Model Assessment – Insulin Resistance) and reduction of fetal macrosomia were observed. Myoinositol also seems to be favorable for overweight or obese women in GDM prevention and treatment. Current findings indicate the positive impact for hormonal changes and restoration in menstrual cyclicity in women with PCOS, improving reproductive disorders in these patients.&#x0D; Conclusions: Overall, although findings are encouraging, further trials for this promising intervention are still required to support oral supplementation of inositol.

Hierarchic regulation of a metabolic pathway: H-NS, CRP, and SsrB control myo-inositol utilization by Salmonella enterica.

The capacity to utilize myo-inositol (MI) as sole carbon and energy source is widespread among bacteria, among them the intestinal pathogen S. Typhimurium. This study elucidates the complex and hierarchical regulation that underlies the utilization of MI by S. Typhimurium under substrate limitation. A total of seven regulatory factors have been identified so far, allowing the pathogen an environment-dependent, efficient, and fine-tuned regulation of a metabolic property that provides growth advantages in different environments.

Effects of Myo-Inositol on the Growth Performance, Digestive Enzyme Activity, and Antioxidation of Juvenile Hucho taimen

Hucho taimen is a cold-water fish with high economic value. Myo-inositol (MI) can accelerate lipid metabolism and promote growth in fish species. The present study aimed to assess the effect of MI on the growth performance, digestive enzyme activity, and antioxidation of juvenile H. taimen. Accordingly, an 8-week feeding trial was conducted. The results demonstrated that increasing MI concentration promoted growth performance in H. taimen. Among the MI concentrations tested, a dose of 328 mg MI/kg corresponded with the lowest feed conversion ratio (FCR) and the highest growth rate. Compared with fish fed a diet of 128 mg MI/kg, the lipase activity in the pyloric caeca significantly increased in fish fed 528 mg MI/kg, while superoxide dismutase (SOD) activity was significantly higher in fish fed 728 mg MI/kg. Consistently, the 128 mg MI/kg diet presented the highest malonaldehyde (MDA) levels. In conclusion, our study revealed that enhanced growth performance, digestive enzyme activity, and antioxidant capacity increased as MI concentration increased. The optimum level of dietary MI in H. taimen was 270–321 mg/kg, based on the FCR and specific growth rate (SGR) on the broken-line regression.

The combination of phosphoinositol with inositol suppresses colorectal cancer growth and metastasis by regulating CLDN23/ RhoA /ROCK1 pathway

Colorectalcancerisa prevalentmalignanttumor, with liver metastases being the primary cause of death. The combination of inositol hexaphosphate (IP6) and inositol (INS) has been shown to inhibit colorectal cancer metastasis.We identified a correlation between CLDN23 expression and the occurrence of liver metastases in colorectal cancer patients. Following the transfection with the lentiviral vector (LV-CLDN23-RNAi), proteomic analysis of SW620 revealed significant alterations in the occludin, ZO-1, RhoA, and ROCK-1 genes expression by western blotting. We found that both SW620 and SW480 cells showed inhibited proliferation, invasion, and migration ability after the treatment with IP6 and INS. Additionally, this combination upregulated occludin and ZO-1, while downregulated CLDN23, RhoA, ROCK-1, and p-MLC2. In conclusion, the combination of IP6 and INS suppressed the proliferation, invasion, and migration of colorectal cancer cells and regulated CLDN23 expression by enhancing tightjunction proteins, such as occludin and ZO1, via the RhoA /ROCK1 pathway.

Myo-inositol improves osmoregulation by promoting lipid utilization in Nile tilapia (Oreochromis niloticus)

This research explores the influence of myo-inositol (MI) on the hypertonic stress adaptation of Nile tilapia (Oreochromis niloticus) by increasing lipid utilization under long-term salinity stress. A two-factor interactive experiment was used, and diets containing either normal lipids (NL, 7%) or high lipids (HL, 15%) contained three MI concentrations of 0, 400, and 1200 mg/kg in each lipid diet. Fish were fed six diets under 20 psu (practical salinity units [psu]) for eight weeks. Under long-term hypertonic stress, dietary MI supplementation significantly improved the growth performance of O. niloticus (P < 0.05). Dietary 1200 mg/kg MI supplementation significantly promoted protein deposition and reduced fat accumulation in the whole fish (P < 0.05). The HL diet significantly caused lipid accumulation in the liver, while dietary 1200 mg/kg MI addition alleviated lipid accumulation by promoting the expression of genes related to lipolysis (PPAR-α; ATGL and CPT) and inhibiting the expression of genes related to lipid synthesis (SREBP; DGAT and FAS) (P < 0.05). In addition, 400 mg/kg MI significantly reduced serum lipids (TG and LDL-C) (P < 0.05). qPCR showed that the purity of dietary 1200 mg/kg MI significantly upregulated the expression of an ion transporter-related gene (NKA) in gills (P < 0.05). Meanwhile, 400 mg/kg and 1200 mg/kg MI significantly affected the content of fatty acids in the liver and gill (P < 0.05). In addition, dietary 1200 mg/kg MI supplementation significantly increased the antioxidant capacity in the liver of O. niloticus. In conclusion, dietary supplementation with 1200 mg/kg MI could regulate lipid metabolism, promote lipid utilization and improve the osmotic regulation ability of O. niloticus.

Alterations of Cerebral Metabolites Are Associated with Frequency of Vasoocclusive Crises and Pain Sensitivity in Patients with Sickle Cell Disease

Purpose Sickle cell disease (SCD) is an inherited hemolytic disorder complicated by acute and chronic pain. Acute vasoocclusive crises (VOCs) associated with SCD are extremely painful episodes that are recurrent, unpredictable, and frequently require hospitalization and opioids for pain control. Changes in brain metabolites were identified in other chronic pain populations but haven't been well studied in SCD. Our ongoing trial (ClinicalTrials.gov Identifier: NCT05045820) aims to evaluate the characteristics of brain metabolites in SCD and understand the relationship between the altered cerebral metabolite(s) and clinical pain in patients with SCD. Materials and Methods Metabolite measurements from a single voxel (size: 2×3×3 cm 3) located within the posterior insula cortex (PIC) were acquired from 26 patients with SCD (31.9 ± 13.9 years, 14-73; 14 females) and 19 healthy controls (HCs) (37.9 ± 16.4 years, 17-62; 10 females) with PRESS (TR/TE = 3000/25 ms, Averages =128) and MEGA-PRESS (TR/TE = 3000/68 ms, Averages =256) sequences using a Siemens Prisma 3T scanner. Written consent was obtained from each participant before scanning. LCModel was used for PRESS analysis to obtain concentration values of glutamine + glutamate (Glx), total creatine (tCr), N-acetylaspartate (NAA), total choline (tCho), and myoinositol (MI). Gannet was used for processing MEGA-PRESS data to estimate GABA+. Ratios of each metabolite to tCr were also quantified. Tissue correction for cerebrospinal fluid was performed for each voxel using the tissue composition estimated from SPM12. The Cramer-Rao Lower Bounds of each metabolite analyzed with LCModel was less than 20%. The frequency of VOCs in the preceding 12 months was recorded for each participant. A moderate pressure pain stimuli (using a 0-100 scale with “0” representing “no pain” and “100” representing “most intense pain imaginable”, pain rating at 40-60 abbreviated as P40 is considered as moderate pain) was delivered via a pressure cuff to the gastrocnemius area of the non-dominant leg using a validated MR-compatible air compressor to induce a tonic pressure pain for 8 min right before MRS scan. Higher pressure intensity (mmHg) of P40 indicated higher pain tolerance and lower pain sensitivity. Correlation between the brain metabolites and pain-related outcomes was studied. Results Due to the large range of age in the SCD group, the brain metabolite profile was compared between 17 SCD patients and 17 ethnicity-, age- and gender-matched HCs. The concentration of Glx (p =0.012) and ratio of Glx to tCr (p =0.034) in PIC were significantly higher in patients with SCD compared to HCs (Figure 1). Within the SCD patient group, there was a significant positive correlation between frequency of VOCs in the preceding 12 months and Glx/tCr (r= 0.39, p=0.047, Spearman's), a significant negative correlation between P40 and Glx (r= -0.46, p=0.019, Spearman's). There were no group differences in any other metabolites. Conclusion We find increased Glx in the PIC in patients with SCD. Previous studies have also found increased Glx and/ or Glx/tCr in the PIC as well as other brain regions including the amygdala, the posterior cingulate, the ventral lateral prefrontal cortex and the anterior insula in fibromyolgia. The PIC is thought to be involved in discriminative activities of sensory pain, which suggests that Glx in PIC is related to pain processing in patients with SCD. Glx/tCr was correlated with frequency of VOCs in patients with SCD, indicating that the SCD patients with higher level of Glx/tCr had more VOCs in the preceding 12 months. In addition, the SCD patients with higher level of Glx had lower pressure intensity of P40, suggesting that elevated Glx in the PIC was related to higher pain sensitivity. Our preliminary data provide the first evidence of a link between alterations in excitatory neurotransmitter levels in the PIC in patients with SCD and indicates new information of potential brain markers for pain in SCD, which may guide treatment. Clinical Relevance Statement: Treatment of pain in SCD remains very challenging in part due to a lack of understanding of the underlying mechanisms and pathophysiology of pain. Brain excitatory neurotransmitters and their relationship with pain have been largely unexplored in SCD. These findings indicate that the relationship between clinical outcomes and excitatory brain neurotransmitters may be a potential objective outcome measure in SCD.

Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions

The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe the consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or "CRISPR D-BUGS," to map phenotypic variants caused by specific designer modifications, known as "bugs." We first fine-mapped a bug in synthetic chromosome II (synII) and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism, and tRNASerCGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating >50% of the Sc2.0 genome in one strain.

Role of myo-inositol in acute kidney injury induced by cisplatin

There is an increasing evidence suggesting that myo-inositol (MI) may be a renoprotective factor. Our previous study revealed that decreased MI concentrations and increased excretion are often observed in animal models of renal injury and in patients with nephropathy. However, the role of MI supplementation in renal injury remains unclear. In this study, we aimed to explore the role of MI in cisplatin-induced acute kidney injury (AKI). We established a model of acute kidney injury caused by cisplatin (CDDP). Male Kunming mice were randomly divided into six groups: Sham (normal saline), CDDP (15 mg/kg), + MI (150 mg/kg), + MI (300 mg/kg), + MI (600 mg/kg) and MI (600 mg/kg). Human renal tubular epithelial cell line HK-2 cells were likewise separated into six groups at random: Control (normal saline), CDDP (20 µM), + MI (200 µM), + MI (400 µM), + MI (800 µM) and MI (800 µM). After the model was established, renal function indexes were subsequently detected, and experiments such as pathological staining analysis and protein expression analysis were performed. Our results showed that cisplatin administration led to AKI and apoptosis in mice and HK-2 cells, accompanied by markedly increased levels of MIOX, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), whereas exogenous MI significantly attenuated kidney injury and HK-2 cell damage induced by cisplatin both in vivo and in vitro by inhibiting excessive apoptosis. Overall, our findings demonstrate that exogenous MI can reduce excessive apoptosis, thus playing a protective role in cisplatin-induced AKI, indicating that exogenous MI may be used as an adjunctive treatment modality in cisplatin-induced AKI.

Microbiome reveals inflammatory-related bacteria and putative functional pathways involved in human papillomavirus-associated penile squamous cell carcinoma.

Penile squamous cell carcinoma (PSCC) is a rare disease that is more prevalent in developing countries, such as Brazil, and is linked to poor genital hygiene, which promotes the proliferation of microorganisms. Dysbiosis has an effect on the local immune response, increases the risk of viral infection, and can generate inflammatory processes. Current knowledge of the microbiota found in penile tissues is limited, and the bacterial diversity of the PSCC remains unknown. In this investigation, the microbiota associated with penile cancer and its potential role in tumor development and progression were identified. The 16S rRNA gene was analyzed by next-generation sequencing in 19 tumors and their respective non-tumor adjacent tissues to perform taxonomic classification, analysis of core microbiome, abundance, and diversity of amplicon sequence variants (ASVs) (QIIME2 v.2020.2), and in silico functional prediction (PICRUST2, p<0.05). In both tissues, the phyla Proteobacteria and Firmicutes, and genera Alcaligenes and Fusobaterium, were the most prevalent. Tumors presented a greater relative abundance of Fusobacteriota, Campilobacteria, and Fusobacterium (p=0.04, p=0.04, and p=0.039, respectively). In addition, the beta diversity analysis revealed a tendency for the formation of two distinct groups when only advanced tumors (pT2 and pT3) were considered. Further, the functional analysis identified the top 35 pathways, and 79.5% of PSCC samples contained pro-inflammatory microorganisms. We describe the first microbiome of penile carcinoma, which revealed an abundant and diverse microbiota as well as inflammatory-related taxa (the phyla Proteobacteria and Firmicutes, the genera Fusobacterium and Prevotella, and the species Finegoldia magma and Pseudomonas geniculata) and molecular pathways (chitin derivates degradation, the protocatechuic acid pathway, inositol metabolism, and the sucrose pathway), which have also been linked to inflammation and carcinogenesis. Moreover, we found specific and abundant ASVs in both tumor and non-tumor tissues. Our data encourage further study to better understand the role of these microorganisms in penile carcinogenesis, offering an opportunity for advances in diagnosis, prognosis, and early therapy.

Efecto de la suplementación con mioinositol en la estructura fisicoquímica de la carga viral en el alimento para gatos contaminados con SARS–CoV–2 mediante la simulación de estornudos

The study was carried to investigate the effect of myo–inositol supplementation on feed physicochemical structure and viral load of dry cat food contaminated with inactive SARS–CoV–2 by simulating sneezing. The most natural infection of severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2) in animals is related to close contact with their owners with COVID–19 which is handling, taking care and feeding them. SARS–CoV–2 can survive on food, fomites and surfaces for extended periods related to environmental conditions. Many natural feed additives and supplements have been a candidate in recent antiviral treatment strategies against COVID–19. In this study, myo–inositol which is permitted in animal nutrition was used at different concentrations (0, 12.5, 25 and 50 mg·100 g-1 cat food) and conditions (22°C at room temperature and 4°C in the refrigerator) to investigate its effects on feed physicochemical structure and viral load of dry cat food contaminated with inactive SARS–CoV–2 by simulating sneezing. For the interactions between myo–inositol, feed structure and viral load, dry matter, moisture, water absorption index (WAI), water solubility index (WSI), pH and virus gene copy (GC) by RT–qPCR were measured. As only storage temperature affected both WAI and WSI as expected, myo–inostol supplementation dose–dependently decreased gene copy in dry cat food (IC50:366.4–581.5 mg·100 g-1 cat food) at 22°C storage temperature. Virus GC did not correlate with the dry matter, moisture content, pH and WAI after the 30 min contact time (except WSI). In conclusion, myo–inositol as a feed additive might have the potential to control serious viral infections such as COVID–19 for human–animal interactions in a One–Health context.

Effect of dietary zinc source, zinc concentration, and exogenous phytase on intestinal phytate degradation products, bone mineralization, and zinc status of broiler chickens

This study aimed to determine the effect of Zn source and dietary level on intestinal myo-inositol hexakisphosphate (InsP6) disappearance, intestinal accumulation of lower InsP and myo-inositol (MI), prececal mineral digestibility, bone mineralization, and Zn status of broilers without and with exogenous phytase in the feed. Male Ross 308 broilers were allocated in groups of 10 to 8 treatments with 8 pens each. Experimental diets were fed from d 7 to d 28 and contained 33 mg/kg dry matter plant-intrinsic Zn. Experimental factors were phytase supplementation (0 or 750 FTU/kg) and Zn source (none [0 mg/kg Zn], Zn-sulfate [30 mg/kg Zn], Zn-oxide [30 mg/kg Zn]). Additional treatments with 90 mg/kg Zn as Zn-sulfate or Zn-oxide and phytase were included to test the effect of Zn level. No Zn source or Zn level effects were observed for ADG, feed conversion ratio, prececal P digestibility, intestinal InsP6 disappearance, and bone ash concentration. However, those measurements were increased by exogenous phytase (P<0.001), except the feed conversion ratio, which was decreased (P<0.001). Ileal MI concentrations were affected by phytase×Zn source interaction (P<0.030). Birds receiving exogenous phytase and Zn supplementation had the highest MI concentrations regardless of exogenous Zn source, whereas MI concentrations were intermediate for birds receiving exogenous phytase only. Exogenous phytase and exogenous Zn source increased the Zn concentration in bone and blood of broilers (P<0.001). In conclusion, measures of exogenous phytase efficacy were not affected by phytase×Zn source interaction. Further studies are needed to rule out an effect from Zn sources other than those tested in this study and to investigate the effect of Zn supplementation on endogenous phosphatases. The missing effect of increasing Zn supplementation from 30 to 90mg/kg in phytase-supplemented diets gives reason to reconsider the Zn supplementation level used by the industry.

Mendelian Randomization Study of Lipid Metabolites Reveals Causal Associations with Heel Bone Mineral Density.

Osteoporosis, which is a bone disease, is characterized by low bone mineral density and an increased risk of fractures. The heel bone mineral density is often used as a representative measure of overall bone mineral density. Lipid metabolism, which includes processes such as fatty acid metabolism, glycerol metabolism, inositol metabolism, bile acid metabolism, carnitine metabolism, ketone body metabolism, sterol and steroid metabolism, etc., may have an impact on changes in bone mineral density. While some studies have reported correlations between lipid metabolism and heel bone mineral density, the overall causal relationship between metabolites and heel bone mineral density remains unclear. to investigate the causal relationship between lipid metabolites and heel bone mineral density using two-sample Mendelian randomization analysis. Summary-level data from large-scale genome-wide association studies were extracted to identify genetic variants linked to lipid metabolite levels. These genetic variants were subsequently employed as instrumental variables in Mendelian randomization analysis to estimate the causal effects of each lipid metabolite on heel bone mineral density. Furthermore, metabolites that could potentially be influenced by causal relationships with bone mineral density were extracted from the KEGG and WikiPathways databases. The causal associations between these downstream metabolites and heel bone mineral density were then examined. Lastly, a sensitivity analysis was conducted to evaluate the robustness of the results and address potential sources of bias. A total of 130 lipid metabolites were analyzed, and it was found that acetylcarnitine, propionylcarnitine, hexadecanedioate, tetradecanedioate, myo-inositol, 1-arachidonoylglycerophosphorine, 1-linoleoylglycerophoethanolamine, and epiandrosterone sulfate had a causal relationship with heel bone mineral density (p < 0.05). Furthermore, our findings also indicate an absence of causal association between the downstream metabolites associated with the aforementioned metabolites identified in the KEGG and WikiPathways databases and heel bone mineral density. This work supports the hypothesis that lipid metabolites have an impact on bone health through demonstrating a causal relationship between specific lipid metabolites and heel bone mineral density. This study has significant implications for the development of new strategies to osteoporosis prevention and treatment.

Changes in the content of D-chiro-inositol and its α-D-galactosyl derivatives during vegetation and desiccation of common buckwheat (Fagopyrum esculentum Moench)

Common buckwheat (Fagopyrum esculentum Moench) is the only crop that contains D-chiro-inositol (DCI) in significant contents in vegetative tissues and its α-D-galactosyl derivatives in seeds. Besides DCI, buckwheat tissues contain small contents of D-pinitol (PIN) and myo-inositol (MIN) and their α-D-galactosyl derivatives. D-chiro-inositol is a health-promoting cyclitol of increasing importance in the treatment of some human diseases. However, changes in DCI content in stems, leaves and maturing buckwheat seeds during plant vegetation and under desiccation were not known. The present study analyzed the concentration of cyclitols and their galactosides in the stems, leaves and seeds of plants harvested on 79th, 94th and 123th days after sowing (DAS) and after desiccation at ambient temperature (23° ±2°C). D-chiro-inositol content in stems and leaves increased with vegetation, while the opposite trend was found in developing and maturing seeds. In the seeds, the accumulation of mono-galactosyl DCI derivatives increased, but at the same time, the content of mono-galactosyl PIN and MIN derivatives decreased. The desiccation process drastically increased the content of di-galactosyl derivatives of DCI and MIN in the seeds. The obtained results suggest a protective role of DCI and MIN di-galactosides against desiccation stress in buckwheat tissues.

Elimination of systemic viral disease in shallot (Allium ascolonicum L) var. Bima Brebes through unconventional approach

Shallot (Allium ascolonicum L), belonging to the genus Allium are propagated vegetatively through layered bulbs. This research aimed to improve the quality of shallots by eliminating OYDV, SLDV viruses through meristematic tissue combined with the antiviral Ribavirin. The research was conducted in the IVEGRI Tissue Culture Laboratory from April to August 2018. Research materials included the infected shallot bulbs of Bima Brebes variety which were previously confirmed by DAS ELISA serology test. Meristematic tissues were cultured on MS + vitamin, MS + supplement media (sucrose 30 gL−1 + Myo inositol 100 mgL−1 + CaP 2 mgL−1 + NAA 0.15 mgL−1 + Kinetin 2 mgL−1 + GA3 0.1 mgL−1 + Gel gro 2gL−1, pH 5.7). A Completely Randomized Design with ten replications was applied for the combinations between antiviral Ribavirin concentrations i.e., 0.5,10,15, 20, 30 mgL−1, and explant size including meristematic tissue (0.5 mm) and shoot tip (2.5 mm). The results obtained through visual observation showed that the additional antiviral Ribavirin and explant size affected the percentage of growth and development of plantlets. Statistical analysis showed that there were no significant interactions between treatments. DAS Elisa serology test showed that the higher the concentration of antiviral Ribavirin the lower the percentage of virus infection.

Investigating the Insulin Sensitizing Effects of Metformin and Myo-Inositol in Polycystic Ovary Syndrome: A Randomized Controlled Trial Protocol

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovulatory dysfunction, hyperandrogenism, and metabolic dysregulation. Insulin resistance (IR) is a common hallmark of PCOS and contributes to metabolic dysfunction. A combination of lifestyle changes and symptom management treatments can help manage the condition. Metformin and myo-inositol (MI) have been shown to improve insulin sensitivity and reduce excess androgen levels in women with PCOS, but there is a lack of research on the effects of combinatory therapy of MI and metformin. This study aims to investigate the hypothesis that a combination of MI and metformin will result in improved insulin sensitivity and clinical outcomes of PCOS. Methods: The study is a double-blinded, randomized controlled trial examining 60 women diagnosed with PCOS that demonstrate the presence of IR. Participants are randomized to one of the following treatments over a six-month period: metformin (MET), inositol (INO), combined metformin and inositol (MET-INO) or placebo-control (CON). BMI, LH:FSH ratio, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were assessed at day 0, day 84 and day 168. Anticipated Results: It is anticipated that the MET-INO group will have the most profound effects following intervention, with a decrease in BMI by 3-4%, a decrease in LH:FSH ratio by 30-40%, and a decrease in HOMA-IR by 1-1.5. MET group is expected to have a significant decrease in BMI by 2-3%, a decrease in LH:FSH ratio by 20-30%, and a decrease in HOMA-IR by 0.5-1.5. The INO group is anticipated to experience a significant decrease in BMI by 1-2%, a decrease in LH:FSH ratio by 10-20%, and a decrease in HOMA-IR by 0.2-0.4. Conclusion: The findings of this study suggest that a combination therapy of metformin and MI may offer a more effective treatment option for improving insulin sensitivity in women with PCOS, compared to metformin or inositol treatment alone. These results have important implications for patients with PCOS and clinicians managing their care. Future studies should further investigate the effectiveness and long-term effects of these treatments.

The Combination of Inositol Hexaphosphate and Inositol Inhibits Metastasis of Colorectal Cancer Cells by Upregulating Claudin 7.

Inositol hexaphosphate (IP6), a widely found natural bioactive substance in grains, effectively inhibits the progression of colorectal cancer (CRC) when used in combination with inositol (INS). We previously showed that supplementation of IP6 and INS upregulated the claudin 7 gene in orthotropic CRC xenografts in mice. The aim of this study was to elucidate the role of claudin 7 in the inhibition of CRC metastasis by IP6 and INS, and explore the underlying mechanisms. We found that IP6, INS and their combination inhibited the epithelial-mesenchymal transition (EMT) of colon cancer cell lines (SW480 and SW620), as indicated by upregulation of claudin 7 and E-cadherin, and downregulation of N-cadherin. The effect of IP6 and INS was stronger compared to either agent alone (combination index < 1). Furthermore, the silencing of the claudin 7 gene diminished the anti-metastatic effects of IP6 and INS on SW480 and SW620 cells. Consistent with in vitro findings, the combination of IP6 and INS suppressed CRC xenograft growth in a mouse model, which was neutralized by claudin 7. Taken together, the combination of IP6 and INS can inhibit CRC metastasis by blocking EMT of tumor cells through upregulation of claudin 7.

Assessment of Symptoms, Pregnancy Outcome, and Health-Related Quality of Life among PCOS women Treated with Myo inositol and Metformin

PCOS is a complicated endocrine disorder that mostly affects between 5% and 10% of women who are of reproductive age. Obesity, hyperandrogenism, and oligo- or anovulation are frequent clinical PCOS signs.&#x0D; Objective: the study was designed to evaluate the effect of combining Metformin and Myoinositol; the main insulin-sensitizing drugs on improving symptoms and HRQOLQ in PCOS women.&#x0D; Materials and Methods: A study was a prospective, interventional, comparative clinical study conducted on 54 patients (aged 18-40 y) who are divided into three groups: group1 patients allocated to receive Myo-inositol(4g), group2 patients allocated to receive Metformin(1g) and group3 patients allocated to receive Myo-inositol(4g) + Metformin(1g) all for 3 months. Baseline and after 3 months, patients’ information and health related quality of life were documented.&#x0D; Result: Metformin and Myoinositol resulted in symptoms improvement within each study groups as (68.8%, 87.5% and 94.1%) for group 1,2 and 3 respectively, only 4 patients from all groups became pregnant. Also, significant change in HRQOLQ in all study groups after three months of treatment were reported.&#x0D; Conclusion: combining Myoinositol with metformin results in improved PCOS symptoms and pregnancy outcome in addition to improved patient’s quality of life.

Myoinositol Versus Metformin in the Treatment of Polycystic Ovarian Syndrome: A Systematic Review.

Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice in the treatment of PCOS is a direct consequence of the lack of sufficient evidence on alternative treatment strategies, as well as a poor understanding of the disorder itself. The aim of our systematic reviewwas to assess the therapeutic advantages and adverse effects of metformin (MET), a standard treatment modality, with myoinositol (MI), a recent substitute that may be used alone or in combination with other remedies to treat PCOS. A literature search was done using PubMed Central, PubMed, Medline, Cochrane, Science Direct, and Google Scholar. Studies were limited to those published in English between 2012 and 2022 that focused on the management of PCOS with both MET and MI. The systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Using standard quality assessment tools, two reviewers independently assessed the content of the incorporated studies. Three meta-analyses, eight randomized controlled trials (RCTs), and one non-randomized non-controlled trial (NN-RCT) were deemed eligible. Following extensive analysis, we found that MET and MI are comparable in their effects on clinical, hormonal, and biochemical profiles. MI, however, had a better safety profile and tolerance due to minimal side effects compared to MET. These results demonstrate the potential role of MI as a novel asset in the armamentarium in the management of PCOS.