Traditional herbal medicines are attaining more popularity and are being widely practiced. Coriandrum sativum L. is one of the oldest herbal medicinal plants valued for its nutritional and medicinal properties. Present investigation was focussed on evaluation of attenuating potential of flavonoid rich extract of C. sativum (FCS) seeds against pathogenic markers of diabetic complications i.e. advanced glycation end products (AGEs), sorbitol and aldose reductase (ALR); by using in-vitro methods. Gas chromatography-mass spectrometry (GC-MS) and Infrared spectroscopy of FCS revealed the presence of different flavonoids. Results demonstrated that FCS has produced 79.80% inhibition of AGEs formation. Additionally, FCS was effective against sorbitol accumulation and ALR inhibition with IC50 values of 221 μg/ml and 6.08 μg/ml respectively. Molecular docking was conducted against three binding site for ALR, RAGEs and sorbitol dehydrogenase to explore their binding interactions with identified flavonoids. The constituents F2, F4 and F6 have shown good binding interactions with all the receptors. The visualisation of the docked complexes revealed the occurrence of hydrophobic forces and hydrogen bonding in receptor and docked constituents. The results were in support with experimental inhibitory activities of FCS against these biomarkers and provide a considerable basis for the identification and development of new inhibitors.

We report an ongoing, protracted and geographically dispersed outbreak of haemolytic uraemic syndrome (HUS) and gastroenteritis in Germany, involving 30 cases since December 2016. The outbreak was caused by the sorbitol-fermenting immotile variant of Shiga toxin-producing (STEC) Escherichia coli O157. Molecular typing revealed close relatedness between isolates from 14 cases. One HUS patient died. Results of a case-control study suggest packaged minced meat as the most likely food vehicle. Food safety investigations are ongoing.

Glycerol and sorbitol are glass-forming hydrogen-bonded systems characterized by intriguing properties which make these systems very interesting also from the applications point of view. The goal of this work is to relate the hydrogen-bonded features, relaxation dynamics, glass transition properties and fragility of these systems, in particular to seek insight into their very different liquid fragilities.

L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity.

In a previous randomized trial, the non-inferiority of two hyaluronic acid injections (Synolis VA versus Synvisc-One) was assessed in patients with knee OA, with a response rate of 79% for Synolis VA. To assess whether a responder profile could be established for this treatment modality, we used the Synolis VA arm of a published 6-month prospective, multicenter, comparative, randomized, double-blinded trial. At baseline and during the study, pain and function were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Ninety-six subjects from the intention-to-treat trial were included in the analysis. The 6-month change of WOMAC Pain with Synolis VA was not associated with any baseline clinical data. However, the change in WOMAC Function was significantly associated with its baseline level, even after adjustment for potential confounding variables (p = 0.028), i.e., a poorer physical function at baseline was associated with a better response. In conclusion, in addition to the high absolute response rate to Synolis VA, the probability of success is even increased if administered in patients with more limited physical function at baseline. Further research with other potential confounding clinical variables is warranted in order to better applicate the concept of personalized medicine.

Rising popularity of phytomedicines in various diseased conditions have strengthened the significance of plant-research and evaluation of phytoextracts in clinical manifestations. Pterocarpus marsupium Roxb., a medicinal plant, known for its anti-oxidant and anti-diabetic activity is a rich source of phytochemicals with antihyperglycemic and antihyperlipidemic activities. However, its possible role in diabetic complications is not evaluated yet. The present study explores the possible role of alcoholic extract of heartwood of P. marsupium in the treatment of long-term diabetic complications. The alcoholic extract of P. marsupium was evaluated for advanced glycation-end-products formation, erythrocyte sorbitol accumulation and rat kidney aldose reductase enzyme inhibition at the concentration of 25-400 μg/ml using in-vitro bioassays. Also the phytoextract at the concentration of 10-320 μg/ml was evaluated for its antioxidant potential by in-vitro antioxidant assays which includes, determination of total phenol content; reducing power assay; nitric oxide scavenging activity; superoxide radical scavenging activity; total antioxidant capacity; total flavonoid content; DPPH scavenging activity; and hydrogen peroxide scavenging activity. The alcoholic extract of P. marsupium across varying concentrations showed inhibitory effect as evident by IC50 on advanced glycation-end-products formation (55.39 μg/ml), sorbitol accumulation (151.00 μg/ml) and rat kidney aldose reductase (195.88 μg/ml). The phytoextract also exhibited high phenolic and flavonoid contents with promising antioxidant potential against the antioxidant assays evaluated. The present investigation suggests that the phytoextract showed prominent antioxidant, antiglycation property and, inhibited accumulation of sorbitol and ALR enzyme, thus promising a beneficial role in reducing/delaying diabetic complications.

The purpose of this work was the studying and modeling of the extraction properties of the sorbitol-based natural deep eutectic solvent (NADES) and sorbitol-based solvents in regard to biologically-active substances (BASs) from Glycyrrhizae roots using theoretical fundamentals based on the laws of statistical physics, thermodynamics, and physical chemistry previously developed by us. In our studies, we used Glycyrrhizae roots, simple maceration, plant raw material:solvent ratio 1:10 w/v, temperature 25 °С, extraction time 24 h; standards of licuroside and glycyram; RP HPLC, differential scanning calorimetry, integral dielectric, impedance and conductivity spectroscopy method of analysis; the following solvents: sorbitol-based NADES sorbitol:malic acid:water (1:1:3 in molar ratio), a modified solvent based on NADES sorbitol:malic acid:water:glycerin (1:1:1:1 in molar ratio) and sorbitol-based solvents sorbitol:ethanol:water at different ratios. It has been found that regression equations for sorbitol-based solvents in coordinates predicted by the theory have a high value of determination coefficient that equals to R²e = 0.993 for glycyram and R²e = 0.976 for licuroside. It has been found that the extraction properties of sorbitol-based NADES with a dielectric constant (ε) equal to 33 ± 2 units are equivalent to those of the sorbitol:ethanol:water solvent with ε = 34 units, and the extraction properties of modified solvent based on NADES with ε = 41 ± 2 units are inferior to those of the sorbitol-ethanol-water solvents with maximum value of BASs yield with the dielectric constant range 40÷50 units. The theoretical fundamentals suggested provide a possibility for an explanation of the mechanism, quantitative description of the extraction properties of the solvent, and target search of the optimal solvent by its dielectric constant.

Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour the idea that diseases can be more efficiently treated when targeting multiple disease-relevant pathways. In CMT1A patients, we therefore tested the potential of PXT3003, a low-dose combination of three already approved compounds (baclofen, naltrexone and sorbitol). Our study conceptually builds on preclinical experiments highlighting a pleiotropic mechanism of action that includes downregulation of PMP22. The primary objective was to assess safety and tolerability of PXT3003. The secondary objective aimed at an exploratory analysis of efficacy of PXT3003 in CMT1A, to be used for designing next clinical development stages (Phase 2b/3).

The aim of the study is to determine the effect of chewing gum containing xylitol and sorbitol on mutans streptococci and Lactobacilli count in saliva, plaque, and gingival health and to compare the efficacy of chewing gums.

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual's susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.

Watercore is a physiological disorder that commonly occurs in sand pear cultivars. The typical symptom of watercore tissue is transparency, and it is often accompanied by browning, breakdown and a bitter taste during fruit ripening. To better understand the molecular mechanisms of watercore affecting fruit quality, this study performed transcriptome and metabolome analyses on watercore pulp from "Akibae" fruit 125 days after flowering. The present study found that the "Akibae" pear watercore pulp contained higher sorbitol and sucrose than healthy fruit. Moreover, the structure of the cell wall was destroyed, and the content of pectin, cellulose and hemicellulose was significantly decreased. In addition, the content of ethanol and acetaldehyde was significantly increased, and the content of polyphenol was significantly decreased. Watercore induced up-regulated expression levels of sorbitol synthesis-related (sorbitol-6-phosphate dehydrogenase, S6PDH) and sucrose synthesis-related genes (sucrose synthesis, SS), whereas it inhibited the expression of sorbitol decomposition-related genes (sorbitol dehydrogenase, SDH) and sorbitol transport genes (sorbitol transporter, SOT). Watercore also strongly induced increased expression levels of cell wall-degrading enzymes (polygalactosidase, PG; ellulase, CX; pectin methylesterase, PME), as well as ethanol synthesis-related (alcohol dehydrogenase, ADH), acetaldehyde synthesis-related (pyruvate decarboxylase, PDC) and polyphenol decomposition-related genes (polyphenol oxidase, PPO). Moreover, the genes that are involved in ethylene (1-aminocyclopropane- 1-carboxylate oxidase, ACO; 1-aminocyclopropane- 1-carboxylate synthase, ACS) and abscisic acid (short-chain alcohol dehydrogenase, SDR; aldehyde oxidase, AAO) synthesis were significantly up-regulated. In addition, the bitter tasting amino acids, alkaloids and polyphenols were significantly increased in watercore tissue. Above all, these findings suggested that the metabolic disorder of sorbitol and sucrose can lead to an increase in plant hormones (abscisic acid and ethylene) and anaerobic respiration, resulting in aggravated fruit rot and the formation of bitter substances.

Changes in microbial community structure are widely known to occur after soil amendment with low-molecular-weight organic compounds; however, there is little information on concurrent changes in soil microbial functional diversity and enzyme activities, especially following sorbitol and mannitol amendment. Soil microbial functional diversity and enzyme activities can be impacted by sorbitol and mannitol, which in turn can alter soil fertility and quality. The objective of this study was to investigate the effects of sorbitol and mannitol addition on microbial functional diversity and enzyme activities. The results demonstrated that sorbitol and mannitol addition altered the soil microbial community structure and improved enzyme activities. Specifically, the addition of sorbitol enhanced the community-level physiological profile (CLPP) compared with the control, whereas the CLPP was significantly inhibited by the addition of mannitol. The results of a varimax rotated component matrix demonstrated that carbohydrates, polymers, and carboxylic acids affected the soil microbial functional structure. Additionally, we found that enzyme activities were affected by both the concentration and type of inputs. In the presence of high concentrations of sorbitol, the urease, catalase, alkaline phosphatase, β-glucosidase, and N-acetyl-β-d-glucosaminidase activities were significantly increased, while invertase activity was decreased. Similarly, this increase in invertase, catalase, and alkaline phosphatase and N-acetyl-β-d-glucosaminidase activities was especially evident after mannitol addition, and urease activity was only slightly affected. In contrast, β-glucosidase activity was suppressed at the highest concentration. These results indicate that microbial community diversity and enzyme activities are significantly affected by soil amendment with sorbitol and mannitol.

HeLa and HCT116 cells respond differentially to sorbitol, an osmolyte able to induce hypertonic stress. In these models, sorbitol promoted the phenotypic manifestations of early apoptosis followed by complete loss of viability in a time-, dose-, and cell type-specific fashion, by eliciting distinct yet partially overlapping molecular pathways. In HCT116 but not in HeLa cells, sorbitol caused the mitochondrial release of the caspase-independent death effector AIF, whereas in both cell lines cytochrome c was retained in mitochondria. Despite cytochrome c retention, HeLa cells exhibited the progressive activation of caspase-3, presumably due to the prior activation of caspase-8. Accordingly, caspase inhibition prevented sorbitol-induced killing in HeLa, but only partially in HCT116 cells. Both the knock-out of Bax in HCT116 cells and the knock-down of Bax in A549 cells by RNA interference reduced the AIF release and/or the mitochondrial alterations. While the knock-down of Bcl-2/Bcl-X(L) sensitized to sorbitol-induced killing, overexpression of a Bcl-2 variant that specifically localizes to mitochondria (but not of the wild-type nor of a endoplasmic reticulum-targeted form) strongly inhibited sorbitol effects. Thus, hyperosmotic stress kills cells by triggering different molecular pathways, which converge at mitochondria where pro- and anti-apoptotic members of the Bcl-2 family exert their control.

The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently induce renal injury via metabolism by fructokinase. Wild-type and fructokinase-deficient mice were subjected to recurrent heat-induced dehydration. One group of each genotype was provided water throughout the day and the other group was hydrated at night, after the dehydration. Both groups received the same total hydration in 24 h. Wild-type mice that received delayed hydration developed renal injury, with elevated serum creatinine, increased urinary NGAL, proximal tubular injury, and renal inflammation and fibrosis. This was associated with activation of the polyol pathway, with increased renal cortical sorbitol and fructose levels. Fructokinase-knockout mice with delayed hydration were protected from renal injury. Thus, recurrent dehydration can induce renal injury via a fructokinase-dependent mechanism, likely from the generation of endogenous fructose via the polyol pathway. Access to sufficient water during the dehydration period can protect mice from developing renal injury. These studies provide a potential mechanism for Mesoamerican nephropathy.

Despite increasing associated mortality and morbidity, the diagnosis of fungal infections, especially with Aspergillus fumigatus (A. fumigatus), remains challenging. Based on known ability of Aspergillus species to utilize sorbitol, we evaluated 2-[18F]-fluorodeoxysorbitol (FDS), a recently described Enterobacterales imaging ligand, in animal models of A. fumigatus infection, in comparison with 2-[18F]-fluorodeoxyglucose (FDG). In vitro assays showed slightly higher 3H-sorbitol uptake by live compared with heat-killed A. fumigatus. However, this was 10.6-fold lower than E. coli uptake. FDS positron emission tomography (PET) imaging of A. fumigatus pneumonia showed low uptake in infected lungs compared with FDG (0.290 ± 0.030 vs. 8.416 ± 0.964 %ID/mL). This uptake was higher than controls (0.098 ± 0.008 %ID/mL) and minimally higher than lung inflammation (0.167 ± 0.007 %ID/mL). In the myositis models, FDS uptake was highest in live E. coli infections. Uptake was low in A. fumigatus myositis model and only slightly higher in live compared with the heat-killed side. In conclusion, we found low uptake of 3H-sorbitol and FDS by A. fumigatus cultures and infection models compared with E. coli, likely due to the need for induction of sorbitol dehydrogenase by sorbitol. Our findings do not support FDS as an Aspergillus imaging agent. At this point, FDS remains more selective for imaging Gram-negative Enterobacterales.

In this study the content and composition of lipids in ergosterol-reduced Sheffersomyces stipitis M12 strain grown on glycerol as a carbon source is determined. Blocking the ergosterol synthesis route in yeast cells is a recently proposed method for increasing S-adenosyl-l-methionine (SAM) production.

DNA polymerase gamma(Pol-gamma) has been shown to be essential for maintenance of the mitochondrial genome (mtDNA) in the petite-positive budding yeast Saccharomyces cerevisiae. Budding yeast cells lacking mitochondria exhibit a slow-growing or petite-colony phenotype. Petite strains fail to grow on non-fermentable carbon sources. However, it is not clear whether the Pol-gamma is required for mtDNA maintenance in the petite-negative fission yeast Schizosaccharomyces pombe.

Sugar and sugar alcohol concentrations were analyzed in subcellular compartments of mesophyll cells, in the apoplast, and in the phloem sap of leaves of Plantago major (common plantain), Plantago maritima (sea plantain), Prunus persica (peach) and Apium graveolens (celery). In addition to sucrose, common plantain, sea plantain, and peach also translocated substantial amounts of sorbitol, whereas celery translocated mannitol as well. Sucrose was always present in vacuole and cytosol of mesophyll cells, whereas sorbitol and mannitol were found in vacuole, stroma, and cytosol in all cases except for sea plantain. The concentration of sorbitol, mannitol and sucrose in phloem sap was 2- to 40-fold higher than that in the cytosol of mesophyll cells. Apoplastic carbohydrate concentrations in all species tested were in the low millimolar range versus high millimolar concentrations in symplastic compartments. Therefore, the concentration ratios between the apoplast and the phloem were very strong, ranging between 20- to 100-fold for sorbitol and mannitol, and between 200- and 2000-fold for sucrose. The woody species, peach, showed the smallest concentration ratios between the cytosol of mesophyll cells and the phloem as well as between the apoplast and the phloem, suggesting a mixture of apoplastic and symplastic phloem loading, in contrast to the herbal plant species (common plantain, sea plantain, celery) which likely exhibit an active loading mode for sorbitol and mannitol as well as sucrose from the apoplast into the phloem.

Currently, nanomaterials face a dilemma due to their advantageous properties and potential risks to human health. Here, a strategy to improve both nanomaterial biocompatibility and functionality is established by screening small metabolites from cells as nanomaterial coatings. A metabolomics analysis of cells exposed to nanosilver (nAg) integrates volcano plots (t-tests and fold change analysis), partial least squares-discriminant analysis (PLS-DA), and significance analysis of microarrays (SAM) and identifies six metabolites (l-aspartic acid, l-malic acid, myoinositol, d-sorbitol, citric acid, and l-cysteine). The further analysis of cell viability, oxidative stress, and cell apoptosis reveals that d-sorbitol markedly reduces nAg cytotoxicity. Subsequently, small molecule loading, surface oxidation, and ionic release experiments support d-sorbitol as the optimal coating for nAg. Importantly, d-sorbitol loading improves the duration of the antibacterial activity of nAg against Escherichia coli and Staphylococcus aureus. The biocidal persistence of nAg-sorbitol is extended beyond 9 h, and the biocidal effects at 12 h are significantly higher than those of naked nAg. This work proposes a new strategy to improve the biocompatibility and functionality of nAg simultaneously by screening small metabolites from cells as nanomaterial functional coatings, a method that can be applied to mitigate the side effects of other nanomaterials.

The influence of polyols on Rhizopus chinensis lipase (RCL) was investigated under high pressure. The poor stability of RCL was observed at 500 MPa at 60 °C without polyols which protected RCL against the loss of activity. The lipase is more stable in phosphate buffer than in tris buffer despite the protection of polyols. The activity was maintained 63% by the sorbitol of 2 mol/L in Tris-HCl buffer but 73% in phosphate buffer after the treatment at 500 MPa and 60 °C for 25 min. The same protective effects could be observed at 1 mol/L of sorbitol, erythritol, xylitol, and mannitol. However, further increase of hydroxyl group number could not significantly improve the enzyme stability. The protection of polyols on RCL appears to depend on both of the polyol nature and the hydroxyl group number. Together with fluorescence spectra, circular dichroism spectra indicated that the chaotic conformation of RCL under high pressure became more ordered with 1 mol/L sorbitol. The results showed that sorbitol effectively stabilized the lipase conformation including the hydrophobic core under extreme conditions. It might be attributed to the interaction of polyols with RCL surface to modify intra-/intermolecular hydrogen bonds, maintaining the hydrophobic interactions within RCL.