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BackgroundThe neurobiology of treatment-resistant schizophrenia (TRS) is poorly understood, and meta-analytic consensus regarding magnetic resonance spectroscopic profiles of glutamate, choline-containing compounds, myo-inositol, and other metabolites in the condition is lacking.MethodsIn this meta-analysis, we examined published findings for N-acetylaspartate, choline-containing compounds (phosphocholine+glycerophosphocholine), myo-inositol, creatine+phosphocreatine, glutamate, and glutamate+glutamine in the anterior cingulate cortex and dorsal striatum in people with TRS versus non-TRS as well as TRS versus healthy control participants (HCs) and TRS versus ultra TRS (i.e., TRS with clozapine resistance). A MEDLINE search revealed 9 articles including 239 people with pooled TRS and ultra TRS, 59 with ultra TRS, 175 with non-TRS, and 153 (HCs) that met meta-analytic criteria.ResultsSignificant effects included higher anterior cingulate cortex phosphocholine+glycerophosphocholine and myo-inositol in the pooled TRS and ultra TRS group than in both the non-TRS group and HCs as well as higher dorsal striatal phosphocholine+glycerophosphocholine in ultra TRS versus HCs, but no differences in other regional metabolites.ConclusionsThe observed metabolite profile in TRS (higher phosphocholine+glycerophosphocholine and myo-inositol signal) is consistent with the hypothesis that TRS has a neuroinflammatory component, although this meta-analysis is not a critical test of that hypothesis. A similar profile is seen in healthy aging, which is known to involve increased neuroinflammation and glial activation. Because the overall number of datasets was low, however, results should be considered preliminary and highlight the need for additional studies of brain metabolites in TRS and their possible association with inflammatory processes.

Inositol pyrophosphates (PP-InsPs) are nutrient messengers whose cellular levels are precisely regulated. Diphosphoinositol pentakisphosphate kinases (PPIP5Ks) generate the active signaling molecule 1,5-InsP8. PPIP5Ks harbor phosphatase domains that hydrolyze PP-InsPs. Plant and Fungi Atypical Dual Specificity Phosphatases (PFA-DSPs) and NUDIX phosphatases (NUDTs) are also involved in PP-InsP degradation. Here, we analyze the relative contributions of the three different phosphatase families to plant PP-InsP catabolism. We report the biochemical characterization of inositol pyrophosphate phosphatases from Arabidopsis and Marchantia polymorpha. Overexpression of different PFA-DSP and NUDT enzymes affects PP-InsP levels and leads to stunted growth phenotypes in Arabidopsis. nudt17/18/21 knock-out mutants have altered PP-InsP pools and gene expression patterns, but no apparent growth defects. In contrast, Marchantia polymorpha Mppfa-dsp1ge, Mpnudt1ge and Mpvip1ge mutants display severe growth and developmental phenotypes and associated changes in cellular PP-InsP levels. Analysis of Mppfa-dsp1geand Mpvip1ge mutants supports a role for PP-InsPs in Marchantia phosphate signaling, and additional functions in nitrate homeostasis and cell wall biogenesis. Simultaneous elimination of two phosphatase activities enhanced the observed growth phenotypes. Taken together, PPIP5K, PFA-DSP and NUDT inositol pyrophosphate phosphatases regulate growth and development by collectively shaping plant PP-InsP pools. Author summary: Organisms must maintain adequate levels of nutrients in their cells and tissues. One such nutrient is phosphorus, an essential building block of cell membranes, nucleic acids and energy metabolites. Plants take up phosphorus in the form of inorganic phosphate and require adequate phosphate levels to support their growth and development. It has been shown that plants and other eukaryotic organisms "measure" cellular phosphate levels using inositol pyrophosphate signaling molecules. The concentration of inositol pyrophosphates serves as a proxy for the cellular concentration of inorganic phosphate, and therefore inositol pyrophosphate synthesis and degradation must be tightly regulated. Here, we report that three different families of enzymes contribute to the degradation of inositol pyrophosphates in plants. Taken together, the different phosphatases shape cellular inositol pyrophosphate pools to regulate inorganic phosphate levels. Loss-of-function mutants of the different enzymes show altered nitrate levels and changes in cell wall architecture, suggesting that inositol pyrophosphates may regulate cellular processes beyond phosphate homeostasis. [ABSTRACT FROM AUTHOR]

This paper describes the synthesis of two 6-azido-6-deoxy derivatives of phosphatidylinositol (PI), which contained different fatty acid chains. These syntheses, starting from methyl α-d-glucopyranoside, employed multiple regioselective transformations with Ferrier rearrangement as one of the key steps. The PI derivatives contained different fatty acid chains in the lipids and an azido group in the inositol residue to facilitate their further functionalization under bioorthogonal conditions. Therefore, they should be useful probes for the investigation of PI and related biology, such as PI phosphorylation, PI interaction with other molecules in cells, and the functions of lipid structures in these processes. [ABSTRACT FROM AUTHOR]

Peach gummosis, a devastating disease caused by Neofusicoccum parvum, significantly shortens peach tree lifespan and reduces the yield of peach trees. Despite its impact, the molecular mechanism underlying this disease remains largely unexplored. In this study, we used RNA-seq, sugar metabolism measurements, and an integrated transcriptional and metabolomic analysis to uncover the molecular events driving peach gummosis. Our results revealed that N. parvum infection drastically altered the transcripts of cell wall degradationrelated genes, the log2Fold change in the transcript level of Prupe.1G088900 encoding xyloglucan endotransglycosylase decreased 2.6-fold, while Prupe.6G075100 encoding expansin increased by 2.58-fold at 12 hpi under N. parvum stress. Additionally, sugar content analysis revealed an increase in maltose, sucrose, L-rhamnose, and inositol levels in the early stages of infection, while D-galactose, D-glucose, D-fructose consistently declined as gummosis progressed. Key genes related to cell wall degradation and starch degradation, as well as UDP-sugar biosynthesis, were significantly upregulated in response to N. parvum. These findings suggest that N. parvum manipulates cell wall degradation and UDP-sugar-related genes to invade peach shoot cells, ultimately triggering gum secretion. Furthermore, weighted gene coexpression network analysis (WGCNA) identified two transcription factors, ERF027 and bZIP9, as central regulators in the downregulated and upregulated modules, respectively. Overall, this study enhances our understanding of the physiological and molecular responses of peach trees to N. parvum infection and provide valuable insights into the mechanisms of peach defense against biotic stresses. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the effect of endoplasmic reticulum (ER) stress sensor inositol‐requiring enzyme 1α (IRE1α) on the sonic hedgehog N‐terminus (N‐Shh)‐enhanced‐osteogenic differentiation process in mouse embryonic fibroblasts (MEFs). Materials and Methods: Osteogenesis of MEFs was observed by alkaline phosphatase (ALP) staining, alizarin red staining, and Von Kossa staining assays. Activation of unfolded protein response and Shh signaling were examined using real‐time quantitative PCR and western blot assays. IRE1α‐deficient MEFs were used to explore the effect of IRE1α on N‐Shh‐driven osteogenesis. Results: N‐Shh increased ALP activity, matrix mineralization, and the expression of Alp and Col‐I in MEFs under osteogenic conditions; notably, this was reversed when combined with the ER stress activator Tm treatment. Interestingly, the administration of N‐Shh decreased the expression of IRE1α. Abrogation of IRE1α increased the expression of Shh pathway factors in osteogenesis‐induced MEFs, contributing to the osteogenic effect of N‐Shh. Moreover, IRE1α‐deficient MEFs exhibited elevated levels of osteogenic markers. Conclusions: Our findings suggest that the IRE1α‐mediated unfolded protein response may alleviate the ossification of MEFs by attenuating Shh signaling. Our research has identified a strategy to inhibit excessive ossification, which may have clinical significance in preventing temporomandibular joint bony ankylosis. [ABSTRACT FROM AUTHOR]

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 polyol phosphates. Some of the possible functions in cosmetics that are reported for this ingredient group are chelating agents, oral care agents, and skin conditioning agents. The Panel reviewed relevant data relating to the safety of these ingredients under the intended conditions of use in cosmetic formulations, and concluded that Sodium Phytate, Phytic Acid, Phytin, and Trisodium Inositol Triphosphate are safe in cosmetics in the present practices of use and concentration described in the safety assessment. The Panel also concluded that the data are insufficient to determine the safety of the following 6 ingredients as used in cosmetics: Disodium Glucose Phosphate, Manganese Fructose Diphosphate, Sodium Mannose Phosphate, Trisodium Fructose Diphosphate, Xylityl Phosphate, and Zinc Fructose Diphosphate. [ABSTRACT FROM AUTHOR]

This study aims to investigate the physicochemical characteristics of the exopolysaccharides (EPS) extracted from the microalgae species Halamphora sp., as well as to evaluate their antioxidant, antibacterial, and anti‐apoptotic activities. The crude extracellular polysaccharides from the halophilic diatom Halamphora sp. were found to be extracellular heterosulfated anionic polysaccharides containing carbohydrates (76.33 ± 1.80%), proteins (0.15 ± 0.02%), uronic acids (5.44 ± 0.08%) and sulfate (7.56 ± 0.86%). The lowest protein (0.24%) and lipid (0.15%) contents suggested that EPS was highly pure. Gas chromatography–mass spectrometry analysis revealed that the carbohydrate fraction consisted of xylose, l‐galactose, d‐galactose, glucose, ribitol, mannose, and inositol with corresponding mole percentages of 40.55, 13.25, 13.00, 9.95, 9.82, 2.90, and 2.28, respectively. In vitro, tests showed a high total antioxidant capacity probably related to l‐galactose followed by d‐galactose, uronic acid, and ribitol. In addition, extracellular polysaccharides (EPS) demonstrated effective antimicrobial Gram + properties with inhibition zones ranging from 10 to 12 mm. Molecular docking showed an antiapoptotic effect, as the best docking score was generated due to the interaction of xylose and caspase 3 (−6.9 kcal/mol) and l‐galactose and caspase 3 (−5 kcal/mol). Overall, the findings of this study suggest the possibility of using the EPS extract of Halamphora sp. as an additive for nutraceutical and cosmetic purposes. [ABSTRACT FROM AUTHOR]

This meeting report discusses the progress in inositol research within the field of polycystic ovary syndrome (PCOS). It highlights the role of inositol as an insulin sensitizer and its involvement in steroidogenesis. The report explores the efficacy of myo-inositol in treating PCOS, including its ability to improve hormonal, reproductive, and metabolic alterations commonly seen in hyperandrogenic PCOS. The authors suggest that the combination of myo-inositol and α-lactalbumin has a synergistic effect that is more effective than myo-inositol alone in treating PCOS. They also propose that PCOS should be stratified into different clinical subtypes for personalized treatment approaches. The study emphasizes the importance of considering factors such as inositol ratios, absorbance rates, and insulin resistance when using inositol therapy for PCOS. [Extracted from the article]

Recent studies strongly suggest that gut microbiome can influence brain functions and contribute to the development of Alzheimer's disease (AD). However, reported changes in the gut microbiomes in AD patients from different countries are not similar, and more research is needed to reveal the relationships between human microbiomes and AD in diverse ethnic populations. There is also an assumption that microbiome‐associated peripheral inflammation might drive the development of sporadic AD. This cross‐sectional study is aimed at analyzing the gut microbial profile and exploring potential associations with blood cytokines and some clinical parameters among individuals diagnosed with Alzheimer's in Kazakhstan. Consistent with previous studies, we have found that the microbial landscape in AD reveals specific alterations in the gut microbiome. Specifically, the AD patient group showed a decreased Firmicutes/Bacteroidetes ratio. The differential abundance analysis highlighted a dysbiosis in the gut microbiota of AD patients, marked by a reduced presence of Bifidobacterium, particularly B. breve. In our study, AD patients' altered gut microbiota composition notably features an increased presence of Pseudomonadota like Phyllobacterium and inflammatory bacteria such as Synergistetes and the Christensenellaceae family. The metabolic profiling of the AD microbiome reveals a predominant presence of pathways related to sugar, carrier molecules, tetrapyrrole, pyrimidine biosynthesis, and nucleic acid processing. This analysis also highlighted a marked reduction in SCFA, carbohydrate, polysaccharide, polyamine, and myo‐inositol degradation pathways. The increases in the proinflammatory cytokines IL‐1a, IL‐8, IL‐17A, IL‐12p40, TNF‐β, MCP‐1, IL‐2, and IL‐12p70 and the anti‐inflammatory cytokines IL‐10 and IL‐13 were observed in AD patients. Key variables driving the separation of AD and controls include inflammatory markers (IL‐1a and IL‐8), growth factors (EGF), lipids (LDL), BMI, and gut microbes, like genus Tyzzerella and Turicibacter and species Parabacteroides distasonis and Bacteroides eggerthii. We have also demonstrated that almost all cytokines strongly correlate with serum adiponectin levels and specific microbial taxa in AD patients. Thus, our findings identify potential microbial and inflammatory signatures in an ethnically distinct cohort of AD patients. These could serve as AD biomarkers and microbiota‐based therapeutic targets for treating AD. [ABSTRACT FROM AUTHOR]

Summary Kernel row number (KRN) is a major yield related trait for maize (Zea mays L.) and is also a major goal of breeders, as it can increase the number of kernels per plant. Thus, identifying new genetic factors involving in KRN formation may accelerate improving yield‐related traits genetically. We herein describe a new kernel number‐related gene (KRN5b) identified from KRN QTL qKRN5b and encoding an inositol polyphosphate 5‐phosphatase (5PTase). KRN5b has phosphatase activity towards PI(4,5)P2, PI(3,4,5)P3, and Ins(1,4,5)P3 in vitro. Knocking out KRN5b caused accumulation of PI(4,5)P2 and Ins(1,4,5)P3, resulting in disordered kernel rows and a decrease in the number of kernels and tassel branches. The introgression of the allele with higher expression abundance into different inbred lines could increase the ear weight of the inbred lines and the corresponding hybrids by 10.1%–12.2% via increasing KRN, with no adverse effects on other agronomic traits. Further analyses showed that KRN5b regulates inflorescence development through affecting the synthesis and distribution of hormones. Together, KRN5b contributes to spikelet pair meristem development through inositol phosphate and phosphatidylinositols, making it a selecting target for yield improvement. [ABSTRACT FROM AUTHOR]

Myo‐inositol may be efficient to improve sperm parameters to increase the chance of fertility. Although, the data are controversial. This study aimed to assess the impact of Myo‐inositol supplements on semen quality and in vitro fertilization (IVF) outcomes. In this systematic review and meta‐analysis, a comprehensive search was conducted in PubMed, Web of Science, and Embase. The objective was to identify relevant human studies that investigated the effects of Myo‐inositol treatment on various sperm factors, such as sperm motility, sperm concentration, sperm morphology, viable spermatozoa, spermatozoa with DNA fragmentation, and pregnancy rate. Additionally, the testosterone levels of patients with Oligo‐astheno‐teratozoospermia (OAT) after Myo‐inositol application were considered. The findings of 16 selected studies from 2240 citations indicated significant improvements in several parameters of sperm after Myo‐inositol administration. Myo‐inositol treatment was associated with a notable increase in total sperm motility (SMD 0.90; 95% CI: 0.34 to 1.46; I2 = 0%, p = .001) and progressive sperm motility (SMD 1.48; 95% CI: 0.37 to 2.59; I2  = 0%, p = .008). Additionally, there was a significant improvement in testosterone levels (SMD 0.54; 95% CI: 0.34 to 0.73; I2  = 0%, p < .0001). Furthermore, Myo‐inositol therapy demonstrated a significant decrease in spermatozoa with DNA fragmentation (SMD −1.37; 95% CI: −2.43 to −0.32; I2  = 85%, p = .01). This study suggests that Myo‐inositol therapy has a positive impact on specific sperm parameters, such as total and progressive sperm motility, along with testosterone levels. These findings provide support for the potential benefits of Myo‐inositol in improving male fertility parameters related to sperm factors. [ABSTRACT FROM AUTHOR]

Micro and nanoscale patterning of surface features and biochemical cues have emerged as tools to precisely direct neurite growth into close proximity with next generation neural prosthesis electrodes. Biophysical cues can exert greater influence on neurite pathfinding compared to the more well studied biochemical cues; yet the signaling events underlying the ability of growth cones to respond to these microfeatures remain obscure. Intracellular Ca2+ signaling plays a critical role in how a growth cone senses and grows in response to various cues (biophysical features, repulsive peptides, chemo-attractive gradients). Here, we investigate the role of inositol triphosphate (IP3) and ryanodine-sensitive receptor (RyR) signaling as sensory neurons (spiral ganglion neurons, SGNs, and dorsal root ganglion neurons, DRGNs) pathfind in response to micropatterned substrates of varied geometries. We find that IP3 and RyR signaling act in the growth cone as they navigate biophysical cues and enable proper guidance to biophysical, chemo-permissive, and chemo-repulsive micropatterns. In response to complex micropatterned geometries, RyR signaling appears to halt growth in response to both topographical features and chemo-repulsive cues. IP3 signaling appears to play a more complex role, as growth cones appear to sense the microfeatures in the presence of xestospongin C but are unable to coordinate turning in response to them. Overall, key Ca2+ signaling elements, IP3 and RyR, are found to be essential for SGNs to pathfind in response to engineered biophysical and biochemical cues. These findings inform efforts to precisely guide neurite regeneration for improved neural prosthesis function, including cochlear implants. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among reproductive-age women. As a leading cause of anovulatory infertility, it complicates fertility treatments, including in vitro fertilization. The widely accepted 2003 Rotterdam diagnostic criteria for PCOS include sub-phenotypes based on variations in androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. In this systematic review, we examined the impacts of inositol and vitamin D on fertility in PCOS. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we used relevant keywords to comprehensively search databases including PubMed, Google Scholar, and MDPI. From an initial pool of 345 articles, 10 met the inclusion criteria. The articles suggest that vitamin D and inositol, particularly myo-inositol and D-chiro-inositol, may represent therapeutic options for PCOS. Vitamin D influences ovarian follicular development, glucose regulation, and insulin sensitivity. When combined with metformin therapy, it is associated with improved menstrual regularity and ovulation. Inositol is crucial for cellular signaling, energy metabolism, glucose regulation, and fertility. This systematic review underscores the importance of investigating inositol and vitamin D within a PCOS management strategy, given the disorder's prevalence and impacts on fertility and metabolic health. Although these agents show promise, additional research could clarify their mechanisms of action and therapeutic benefits. This review emphasizes the need for exploration of effective treatments to improve the quality of life among individuals with PCOS. Inositol and vitamin D represent potential options, but more studies are required to elucidate their roles in the management of this condition. [ABSTRACT FROM AUTHOR]

α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium‐dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium‐dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq‐protein, phospholipase Cβ‐mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3‐receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper‐excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G‐proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq‐protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines. [ABSTRACT FROM AUTHOR]

Lameness due to bacterial chondronecrosis with osteomyelitis (BCO) is an infection of weak bone by opportunistic bacteria that infiltrate the circulation as a result of immune suppression or gastrointestinal deterioration. One mitigating strategy is the dietary inclusion of products to support overall broiler robustness and bone health. To test the ability of phytase and stimbiotic supplements to alleviate lameness, broilers were reared for 56 days on either litter flooring or wire ramps to induce BCO and fed one of 6 diets: positive control (PC); negative control (NC, Ca and P deficient); PC plus stimbiotic; PC plus stimbiotic and phytase; NC plus phytase; NC plus stimbiotic and phytase. Stimbiotic was added at 100 g/tonne, and phytase at 3000 FTU/kg. Birds were scored for BCO on d56, or when culled for lameness. All-cause mortality was higher on ramp as compared to litter, regardless of treatment. Lameness was significantly induced by wire ramps, with the greatest incidence in the NC diet. Importantly, the addition of stimbiotic and phytase to the NC diet reduced lameness by ∼50%. Femur BCO scores were similarly reduced, with ∼60% of femurs scored ≥1 in the NC group compared to 30–37% in stimbiotic and phytase supplemented groups, indicating that these supplements can impact the onset/progression of lameness in poultry. There was no correlation between plasma and bone inositol levels; however, wire flooring reduced bone inositol, regardless of diet. Additionally, blood pH was greater and circulating PCO2, HCO3, BE, TCO2, K, haematocrit, and haemoglobin were lower on ramp compared to litter flooring. RESEARCH HIGHLIGHTS: Wire ramp model reproducibly induced lameness/BCO in broilers. Treatments did not affect growth, but phytase with stimbiotic significantly reduced BCO. Phytase increased circulating inositol, and wire flooring decreased bone inositol. [ABSTRACT FROM AUTHOR]

Myo-inositol-1-phosphate synthase (MIPS) catalyzes the NAD+-dependent isomerization of glucose-6-phosphate (G6P) into inositol-1-phosphate (IMP), controlling the rate-limiting step of the inositol pathway. Previous structural studies focused on the detailed molecular mechanism, neglecting large-scale conformational changes that drive the function of this 240 kDa homotetrameric complex. In this study, we identified the active, endogenous MIPS in cell extracts from the thermophilic fungus Thermochaetoides thermophila. By resolving the native structure at 2.48 Å (FSC = 0.143), we revealed a fully populated active site. Utilizing 3D variability analysis, we uncovered conformational states of MIPS, enabling us to directly visualize an order-to-disorder transition at its catalytic center. An acyclic intermediate of G6P occupied the active site in two out of the three conformational states, indicating a catalytic mechanism where electrostatic stabilization of high-energy intermediates plays a crucial role. Examination of all isomerases with known structures revealed similar fluctuations in secondary structure within their active sites. Based on these findings, we established a conformational selection model that governs substrate binding and eventually inositol availability. In particular, the ground state of MIPS demonstrates structural configurations regardless of substrate binding, a pattern observed across various isomerases. These findings contribute to the understanding of MIPS structure-based function, serving as a template for future studies targeting regulation and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Introduction & Methods: The aim of the study is to assess the Role of Myoinositol & Metformin on clinical, hormonal & metabolic profile of patients in Poly cystic Ovarian Syndrome. The women started with the intake of Myoinositol at a dosage of 2000 mg and 500 mg metformin used for a period of 01 Year. The primary outcome of the study was to determine the restoration of normal menstrual cycles, improvement in acne, reduction in hirsutism, weight loss & fertility. Results: We found maximum cases in 25-29.9 i.e. 51%. BMI - The chi-square statistic is 0.0003. The p-value is .047363. The result is significant at p < .05. Mean fasting blood glucose - 93.44±8.27. Mean Ultrasound Pelvis - 16.92±4.48 & Mean TSH - 2.73±2.66 Conclusion: In the present study, both Metformin and MI were equally effective in improving the clinical, metabolic, and hormonal profile in PCOS patients. BMI was significantly reduced by both the metformin and MI after 12 weeks of treatment. According to the available evidence on this molecule derived from inositol, MYO should be considered an effective and safe treatment for obese and non-obese women with PCOS with insulin resistance and hyperinsulinemia, administered with the aim of improving oocyte quality and maturation and the reproductive prognosis in patients. Treatment with metformin (MET) ameliorated the insulin sensitivity and decreased the androgens levels, but the limitations to MET use are its gastrointestinal side effects. [ABSTRACT FROM AUTHOR]

Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy. [ABSTRACT FROM AUTHOR]

1. Tibial dyschondroplasia (TD) is a skeletal disorder in broilers that has financial implications, necessitating dietary modifications to reduce the prevalence of this disease. This study explored how arginine silicate inositol complex (ASI) supplementation affected tibial growth plate (TGP) and overall bone health in broilers with manganese (Mn) deficiency-induced TD. 2. A total of 240 broiler chicks were divided into four groups, each consisting of 60 birds (15 replicates of four broilers each) as follows: i) Control, with 60 mg Mn per kg of diet; ii) ASI, with 60 mg Mn and 1 g ASI per kg of diet; iii) TD, with 22 mg Mn per kg of diet, and iv) TD+ASI, with 22 mg Mn and 1 g ASI per kg of diet. 3. It was found that ASI supplementation increased tibial bone length in Mn-deficient TD broilers (p = 0.007). There was no Mn x ASI interaction for other bone morphometry variables (p > 0.05). However, both tibial bone mineral content and density were affected by Mn and ASI (p < 0.05). With ASI supplementation, serum bone-specific alkaline phosphatase and osteocalcin levels were elevated in the TD+ASI group compared to the TD group (p < 0.001). In the TD group, osteoprotegerin (OPG) levels in the TGP decreased compared to the control groups (p < 0.001). 4. In contrast, ASI supplementation in the TD broilers counteracted the decrease in OPG compared to TD broilers without ASI supplementation (p < 0.001). The Mn level and ASI supplementation significantly influenced the OPG/receptor activator of the nuclear factor-κB ligand ratio (p < 0.001). 5. In conclusion, the results demonstrated that inclusion of ASI in broiler diets could enhance bone formation variables by controlling OPG levels in the TGP, potentially serving as an effective method to decrease the occurrence of TD. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m²). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions. [ABSTRACT FROM AUTHOR]

Introduction: We sought to conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the impact of myo-inositol on oocyte and embryo quality in women undergoing assisted reproduction. Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist (registration number: CRD42023433328). Studies were identified by searching PubMed, Cochrane Library, Google Scholar, Scopus, Embase, and ClinicalTrials databases. Results: Eight RCTs were included for qualitative analysis reporting on 820 participants. Four meta-analyses were performed. Numbers of retrieved oocytes in comparison of intervention and control group were higher in inositol group (mean difference [MD] = 0.41, 95% CI: 0.05–0.77, p = 0.02). Meta-analysis of two studies comparing numbers of oocytes among poor ovarian responder patients showed no significant difference between intervention and control group (MD = 0.50, 95% CI: 0.57–1.58, p = 0.36). Miscarriage rate has no statistically significant difference between the treatment and control groups (risk ratios [RRs] = 0.81, 95% CI: 0.20–3.32, p = 0.77). Inositol played no role in improving clinical pregnancy rates; there was no significant difference between the intervention group and the control group (RR = 1.41, 95% CI: 0.88–2.25, p = 0.15). Conclusion: Thus, we did not find any benefits of using myo-inositol on oocyte and embryo quality in women undergoing reproductive technologies. Further studies are needed to assess efficacy, safety, and high compliance by female patients. [ABSTRACT FROM AUTHOR]

The posterior cingulate cortex (PCC) is a key hub of the default mode network and is known to play an important role in attention. Using ultra-high field 7 Tesla magnetic resonance spectroscopy (MRS) to quantify neurometabolite concentrations, this exploratory study investigated the effect of the concentrations of myo-inositol (Myo-Ins), glutamate (Glu), glutamine (Gln), aspartate or aspartic acid (Asp) and gamma-amino-butyric acid (GABA) in the PCC on attention in forty-six healthy participants. Each participant underwent an MRS scan and cognitive testing, consisting of a trail-making test (TMT A/B) and a test of attentional performance. After a multiple regression analysis and bootstrapping for correction, the findings show that Myo-Ins and Asp significantly influence (p < 0.05) attentional tasks. On one hand, Myo-Ins shows it can improve the completion times of both TMT A and TMT B. On the other hand, an increase in aspartate leads to more mistakes in Go/No-go tasks and shows a trend towards enhancing reaction time in Go/No-go tasks and stability of alertness without signal. No significant (p > 0.05) influence of Glu, Gln and GABA was observed. [ABSTRACT FROM AUTHOR]

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Persimmon fruits are brightly colored and nutritious and are fruits that contain large amounts of sugar, vitamins, mineral elements, and phenolic substances. The aim of this study was to explore the differences in fruit-sugar components of different persimmon germplasms and their relationships with phenotypic and flavor indices through the determination of phenotypes and sugar components and through electronic-tongue indices, which provided the basis and inspiration for the selection of different sugar-accumulating types of persimmon fruits and the selection of high-sugar persimmon varieties. Our results showed that persimmon germplasm fruit-sugar components were dominated by sucrose, glucose and fructose and that the remaining sugar components were more diverse but less distributed among the various germplasm types. Based on the proportion of each sugar component in the fruit, persimmon germplasms can be categorized into sucrose-accumulating and reduced-sugar-accumulation types. Sucrose-accumulating types are dominated by sucrose, galactose, fucose and inositol, while reduced-sugar-accumulation types are dominated by glucose, fructose, mannose-6-phosphate, and xylose. The content of sugar components in the germplasm persimmon of fruits of different types and maturity periods of also differed, with significant differences in sugar components between PCNA (pollination-constant non-astringent) and PCA (pollination-constant astringent) fruits. Cluster analysis classified 81 persimmon germplasms into three clusters, including cluster I-A, with low glucose and fructose content, and cluster I-B, with medium glucose, fructose, and sucrose contents. Cluster II was high in sucrose and fructose. Cluster III had high contents of glucose and fructose and low contents of sucrose and inositol. [ABSTRACT FROM AUTHOR]

Grains and beans are abundant in bioactive substances.This study investigated the bioactive substances in a multi-grains formula (MGF) composed of mung bean, tartary buckwheat, black rice, black sticky rice, oat germ rice, and white rice.Polyphenols and inositol (PIEs) were extracted from MGF before and after high-temperature air fluidization (HTAF) processing, and the antioxidant activity of the extract was evaluated in vitro.Results showed that the PIEs of MGF mainly contained phenolic acids, flavonoids, myo-inositol, and D-chiro-inositol.The highest scavenging rate of MGF PIEs for ABTS cationic free radicals, DPPH free radicals, and hydroxyl free radicals reached 92.28%, 75.02%, and 87.21%, respectively, and its scavenging ability increased in a concentration-dependent manner within a certain concentration range.At the same time, MGF PIEs also showed a certain total reducing capacity and Fe2+ chelating capacity, with the highest reaching 1.26 mg vitamin C equivalent /mL and 1.85 mmol Fe2+, respectively.After the HTAF process, the scavenging abilities for DPPH free radicals, total reducing capacity, and Fe2+ chelating capacity of MGF were further improved.The correlation analysis showed that total flavonoids and total polyphenols were the most critical antioxidant components of MGF.Their contents were significantly correlated with ABTS cationic radical scavenging capacity, hydroxyl radical scavenging capacity, and total reducing capacity (P<0.001), and the correlation was higher than that of myo-inositol and D-chiro-inositol (P<0.01).The total reducing capacity was the most representative antioxidant evaluation index of MGF.It was significantly correlated with total polyphenols (P<0.001), total flavonoids (P<0.001), myo-inositol (P<0.001), and D-chiro-inositol (P<0.01) contents.To sum up, the PIEs of MGF showed strong antioxidant activity, and HTAF treatment which improved the cooking quality of MGF could also retain or slightly improve the antioxidant activity of MGF.This research provided a certain theoretical basis for the prevention of oxidative stress metabolic diseases via multi-grain diets. [ABSTRACT FROM AUTHOR]

In the post-harvest phase, fruit is inexorably subjected to extrinsic stressors that expedite energy expenditure and truncate the storage lifespan. The present study endeavors to elucidate the response strategies of litchi to the alterations of energy state caused by 2,4-Dinitrophenol (DNP) treatment through energy metabolism and sugar metabolism. It was observed that the DNP treatment reduced the energy state of the fruit, exacerbated membrane damage and triggered rapid browning in the pericarp after 24 h of storage. Furthermore, the expression of genes germane to energy metabolism (LcAtpB, LcAOX1, LcUCP1, LcAAC1, and, LcSnRK2) reached their peak within the initial 24 h of storage, accompanied by an elevation in the respiratory rate, which effectively suppressed the rise in browning index of litchi pericarp. The study also posits that, to cope with the decrease of energy levels and membrane damage, litchi may augment the concentrations of fructose, glucose, inositol, galactose, and sorbose, thus safeguarding the canonical metabolic functions of the fruit. Collectively, these findings suggest that litchi can modulate energy and sugar metabolism to cope with fruit senescence under conditions of energy deficiency. This study significantly advances the understanding of the physiological responses exhibited by litchi fruit to post-harvest external stressors. [ABSTRACT FROM AUTHOR]

Effect of succinic acid on the processes of myogenesis was investigated in the study with the cells of C2C12 line. In the concentration range 10-1000 µM, succinic acid stimulated the process of myogenic differentiation, increasing the levels of myogenesis factors MyoD (at all stages of myogenesis) and myogenin (at the stage of terminal differentiation). Presence of the succinate receptors SUCNR1 was revealed in the C2C12 cells using Western blotting, level of which decreased during myogenesis. When succinic acid was added to the cells, the level of intracellular succinate did not change significantly and decreased during myogenic differentiation. Using a specific Gai protein inhibitor, pertussis toxin, it was found that stimulation of myogenesis in the C2C12 cells under the action of succinic acid is realized through SUCNR1–Gai interaction. [ABSTRACT FROM AUTHOR]

In the fullerene cone HIV-1 capsid, the central channels of the hexameric and pentameric capsomers each contain a ring of arginine (Arg18) residues that perform essential roles in capsid assembly and function. In both the hexamer and pentamer, the Arg18 rings coordinate inositol hexakisphosphate, an assembly and stability factor for the capsid. Previously, it was shown that amino-acid substitutions of Arg18 can promote pentamer incorporation into capsid-like particles (CLPs) that spontaneously assemble in vitro under high-salt conditions. Here, we show that these Arg18 mutant CLPs contain a non-canonical pentamer conformation and distinct lattice characteristics that do not follow the fullerene geometry of retroviral capsids. The Arg18 mutant pentamers resemble the hexamer in intra-oligomeric contacts and form a unique tetramer-of-pentamers that allows for incorporation of an octahedral vertex with a cross-shaped opening in the hexagonal capsid lattice. Our findings highlight an unexpected degree of structural plasticity in HIV-1 capsid assembly. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a metabolic chronic disease in which insulin resistance and insufficient insulin production lead to elevated blood glucose levels. The prevalence of T2D is growing worldwide, mainly due to obesity and the adoption of Western diets. Replacing animal foods with healthy plant foods is associated with a lower risk of T2D in prospective studies. In randomized controlled trials, the consumption of healthy plant foods in place of animal foods led to cardiometabolic improvements in patients with T2D or who were at high risk of the disease. Dietary patterns that limit or exclude animal foods and focus on healthy plant foods (eg, fruits, vegetables, whole grains, nuts, legumes), known as healthy, plant-based diets, are consistently associated with a lower risk of T2D in cohort studies. The aim of this review is to examine the differential effects of plant foods and animal foods on T2D risk and to describe the existing literature about the role of healthy, plant-based diets, particularly healthy vegan diets, in T2D prevention and management. The evidence from cohort studies and randomized controlled trials will be reported, in addition to the potential biological mechanisms that seem to be involved. [ABSTRACT FROM AUTHOR]

Two new inositol compounds, myoinositol-1,3-di-4-hydroxybenzoyl-2-methylbutyrate (1) and myoinositol-1,3-di-4-hydroxybenzoyl-2-isobutyrate (2), along with two known ones, were isolated from Thalictrum scabrifolium var. leve Franch., and their structures were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited activities to inhibit Staphylococcus epidermidis with an MIC of 5.00 mg/mL and 4.50 mg/mL at a concentration of 5 mg/mL. Moreover, they had a certain inhibitory effect on Escherichia coli and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Seawater (SW)-acclimated Nile tilapia, Oreochromis niloticus, reared under a salinity 30 environment had lower growth and survival than the freshwater (FW)-acclimated fish. It was hypothesized that cells of the SWacclimated fish had not been able to synthesize an adequate level of a compatible osmolyte, myo-inositol (MI), in adjusting to the salinity 30 environment. In this study, MI supplements, at 250, 500, and 750 mg/kg pellets, were provided to the fish through top-dressing. After the 30-day feeding trial, the following parameters were determined: final body weights; survival; biomass increase; feed conversion ratio (FCR); plasma osmolality and ions; and two transcripts in the gills mips250 and mipa1 encoding enzymes responsible for MI biosynthesis. The SW-acclimated O. niloticus receiving 500-mg MI supplement had significantly higher survival, biomass increase, and lower FCR than those of the SW-acclimated fish receiving no supplement. At 500-mg MI supplemental level, the increasing values of plasma osmolality and Na+ observed in SW-acclimated fish were significantly attenuated. The transcript mipa1, but not mips250, was markedly up-regulated in the SW-acclimated O. niloticus, compared with that of the FW-acclimated fish. Again, MI at 500-mg supplement attenuated the upregulation significantly. This study suggests that MI supplement at the optimum level enhanced the performance of SW-acclimated O. niloticus, and through yet unknown mechanisms, attenuated some of their physiological responses to the osmotic stress. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as therapeutic agents for targeting human disease pathways; however, there is still much to be uncovered about their mechanism of gene regulation. Alopecia areata (AA) is a commonly occurring inflammatory condition characterized by the infiltration of T cells that specifically target the anagen‐stage hair follicle. The limited understanding of its precise cellular mechanism may be the reason behind the scarcity of effective treatments for AA. Aim: The significance and function of hsa‐miR‐193a‐5p as a genetic marker for AA and its potential influence on the advancement of the disease. Subjects and methods: A case‐control study comprised 77 individuals diagnosed with AA who were matched with 75 healthy controls. In order to measure the expression of miR‐200c‐3p in both groups, the real‐time PCR technique was utilized. The prediction of suitable genes for hsa‐miR‐193a‐5p, as well as the identification of pathways and gene‐gene interactions, were carried out using bioinformatic tools. Results: The levels of hsa‐miR‐193a‐5p expression were notably elevated in AA patients in comparison to healthy controls. Our prediction suggests that the involvement of hsa‐miR‐193a‐5p in the development of AA is significant due to its influence on the inositol phosphorylation pathway and the Phosphatidylinositol signaling system, achieved through its direct impact on the IPPK gene. Conclusion: For the first time, our study demonstrates the significant over‐expression of a new miRNA, hsa‐miR‐193a‐5p, in the blood of AA patients compared to controls, and highlights its impact on the IPPK gene and the inositol phosphorylation and Phosphatidylinositol signaling pathways, suggesting a potential therapeutic role for hsa‐miR‐193a‐5p in AA. [ABSTRACT FROM AUTHOR]

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are highconductance channels that allow the regulated redistribution of Ca2+ from the endoplasmic reticulum (ER) to the cytosol and, at specialized membrane contact sites (MCSs), to other organelles. Only a subset of IP3Rs release Ca2+ to the cytosol in response to IP3. These 'licensed' IP3Rs are associated with Kras-induced actin-interacting protein (KRAP, also known as ITPRID2) beneath the plasma membrane. It is unclear whether KRAP regulates IP3Rs at MCSs. We show, using simultaneous measurements of Ca2+ concentration in the cytosol and mitochondrial matrix, that KRAP also licenses IP3Rs to release Ca2+ to mitochondria. Loss of KRAP abolishes cytosolic and mitochondrial Ca2+ signals evoked by stimulation of IP3Rs via endogenous receptors. KRAP is located at ER-mitochondrial membrane contact sites (ERMCSs) populated by IP3R clusters. Using a proximity ligation assay between IP3R and voltage-dependent anion channel 1 (VDAC1), we show that loss of KRAP reduces the number of ERMCSs. We conclude that KRAP regulates Ca2+ transfer fromIP3Rs tomitochondria by both licensing IP3R activity and stabilizing ERMCSs. [ABSTRACT FROM AUTHOR]