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The enzymes used for D-allose production generally failed to meet the requirements of industrial production of D-allose in terms of enzyme activity and catalytic efficiency. In this study, 13 single mutants of CfRpiB (Ribose-5-phosphate isomerase from Curtobacterium flaccumfaciens) were constructed by combining site-specific mutations and ring-open residue mutations with rational design. It was found that the enzyme activities of all 13 single mutants were positively changed relative to the wild type. Among them, the single mutant with the highest increase in enzyme activity was C72M, which increased its enzyme activity by 30 %. On this basis, three iterative mutant strains were constructed, among which C72M/S105H increased the yield of D-allose by 2.62 times. Especially, enzymatic property measurements showed that its enzyme activity increased by 50 %. Molecular docking of the C72M/S105H mutant with D-allulose revealed that the increased enzymatic activity of the mutant C72M/S105H could be attributed to the smaller substrate binding site and tighter binding to the substrate. This study further reveals the relationship between mutation sites and enzymatic properties, demonstrating the feasibility of improving the efficiency of preparing rare sugars through enzyme molecular modification. Synopsis: Site-directed mutagenesis of binding sites and open-open loop residues and explored the reasons for the enhanced activity of the mutated enzyme. [Display omitted] • 13 single mutants are designed based on amino acid chain length and surface charge. • 30 % increase in enzyme activity of single mutant compared to wild type. • Iterative mutant strain C72M/S105H increases conversion of D-allulose by 2.62-fold. • The improved enzymatic properties of C72M/S105H are due to a tighter binding site. [ABSTRACT FROM AUTHOR]

Enzymatic preparation of rare sugars as an alternative to traditional sweeteners is an effective strategy to achieve a low-calorie healthy diet. Ribose-5-phosphate isomerase B (RpiB) is a key enzyme in the non-oxidative branch of the catalytic pentose phosphate pathway. Here, we investigated the potential of Curtobacterium flaccumfaciens ZXL1 (C. flaccumfaciens ZXL1) derived RpiB (CfRpiB) in D-allose preparation. The optimal reaction conditions for recombinant CfRpiB were found experimentally to be pH 7.0, 55 °C, and no metal ions. The kinetic parameters Km, kcat, and catalytic efficiency kcat/Km were 320 mM, 4769 s−1, and 14.9 mM−1 s−1 respectively. The conversion of D-allulose by purified enzyme (1 g L−1 ) to D-allose was 13% within 1 h. In addition, homology modeling and molecular docking were used to predict the active site residues: Asp13, Asp14, Cys72, Gly73, Thr74, Gly77, Asn106, and Lys144. [ABSTRACT FROM AUTHOR]

Age-related physical and cognitive decline may be ameliorated by consuming functional foods. d-Allose, reported to have multiple health benefits, may temper aging phenotypes, particularly brain function. We investigated whether d-allose supplementation improves cognitive function. A standard battery of behavioral tests was administered to 18-month-old male mice after consuming diet containing 3 % d-allose for 6 months. Following a wire-hanging test, an open-field test, Morris water maze, fear-conditioning, and an analgesia test were sequentially performed. Bone density and strength were assessed afterwards. Possible mechanism(s) under-lying memory changes in hippocampus were also examined with a DNA microarray. d-Allose failed to influence muscle strength, locomotor activity and anxiety, fear memory, or pain sensitivity. However, d-allose improved hippocampus-dependent spatial learning and memory, and it may contribute to increase bone strength. d-Allose also changed the expression of some genes in hippocampus involved in cognitive functions. Long-term d-allose supplementation appears to modestly change aging phenotypes and improve spatial memory.

AbstractD-allose, a C-3 epimer of D-glucose and an aldose-ketose isomer of D-allulose, exhibits 80% of sucrose’s sweetness while being remarkably low in calories and nontoxic, making it an appealing sucrose substitute. Its diverse physiological functions, particularly potent anticancer and antitumor effects, render it a promising candidate for clinical treatment, garnering sustained attention. However, its limited availability in natural sources and the challenges associated with chemical synthesis necessitate exploring biosynthetic strategies to enhance production. This overview encapsulates recent advancements in D-allose’s physicochemical properties, physiological functions, applications, and biosynthesis. It also briefly discusses the crucial role of understanding aldoketose isomerase structure and optimizing its performance in D-allose synthesis. Furthermore, it delves into the challenges and future perspectives in D-allose bioproduction. Early efforts focused on identifying and characterizing enzymes responsible for D-allose production, followed by detailed crystal structure analysis to improve performance through molecular modification. Strategies such as enzyme immobilization and implementing multi-enzyme cascade reactions, utilizing more cost-effective feedstocks, were explored. Despite progress, challenges remain, including the lack of efficient high-throughput screening methods for enzyme modification, the need for food-grade expression systems, the establishment of ordered substrate channels in multi-enzyme cascade reactions, and the development of downstream separation and purification processes. [ABSTRACT FROM AUTHOR]

Abstract Background Ischemic stroke (IS) occurs when a blood vessel supplying the brain becomes obstructed, resulting in cerebral ischemia. This type of stroke accounts for approximately 87% of all strokes. Globally, IS leads to high mortality and poor prognosis and is associated with neuroinflammation and neuronal apoptosis. D-allose is a bio-substrate of glucose that is widely expressed in many plants. Our previous study showed that D-allose exerted neuroprotective effects against acute cerebral ischemic/reperfusion (I/R) injury by reducing neuroinflammation. Here, we aimed to clarify the beneficial effects D-allose in suppressing IS-induced neuroinflammation damage, cytotoxicity, neuronal apoptosis and neurological deficits and the underlying mechanism in vitro and in vivo. Methods In vivo, an I/R model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 N mice, and D-allose was given by intraperitoneal injection within 5 min after reperfusion. In vitro, mouse hippocampal neuronal cells (HT-22) with oxygen–glucose deprivation and reperfusion (OGD/R) were established as a cell model of IS. Neurological scores, some cytokines, cytotoxicity and apoptosis in the brain and cell lines were measured. Moreover, Gal-3 short hairpin RNAs, lentiviruses and adeno-associated viruses were used to modulate Gal-3 expression in neurons in vitro and in vivo to reveal the molecular mechanism. Results D-allose alleviated cytotoxicity, including cell viability, LDH release and apoptosis, in HT-22 cells after OGD/R, which also alleviated brain injury, as indicated by lesion volume, brain edema, neuronal apoptosis, and neurological functional deficits, in a mouse model of I/R. Moreover, D-allose decreased the release of inflammatory factors, such as IL-1β, IL-6 and TNF-α. Furthermore, the expression of Gal-3 was increased by I/R in wild-type mice and HT-22 cells, and this factor further bound to TLR4, as confirmed by three-dimensional structure prediction and Co-IP. Silencing the Gal-3 gene with shRNAs decreased the activation of TLR4 signaling and alleviated IS-induced neuroinflammation, apoptosis and brain injury. Importantly, the loss of Gal-3 enhanced the D-allose-mediated protection against I/R-induced HT-22 cell injury, inflammatory insults and apoptosis, whereas activation of TLR4 by the selective agonist LPS increased the degree of neuronal injury and abolished the protective effects of D-allose. Conclusions In summary, D-allose plays a crucial role in inhibiting inflammation after IS by suppressing Gal-3/TLR4/PI3K/AKT signaling pathway in vitro and in vivo.

Background: Rare sugars, which exist only in very small quantities in nature, have recently attracted attention for their various biological functions in medicine. Among them, d-allose is known to have cytoprotective effects by antioxidant effects. In this study, we investigated whether the antioxidant effects of d-allose reduce brain edema in a water intoxication model of cytotoxic brain edema. Methods: Mice were injected intraperitoneally with distilled water (10 % of body weight) to create a model of brain edema. d-allose was administered orally at 400 mg/kg 30 min before the model was created. Two hours later, the degree of brain edema was measured by the dry-weight method to determine whether d-allose reduced brain edema. As an index of antioxidant effects, we measured changes over time in inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) induced by the water intoxication model, and whether d-allose reduced inflammatory cytokines 4 h after model creation. Results: Administration of d-allose significantly suppressed brain edema formation of the water-intoxication model. And it significantly reduced inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6). These results suggest that the antioxidant effect of d-allose exerts an anti-inflammatory effect and reduces brain edema.

Background: Ischemic stroke (IS) occurs when a blood vessel supplying the brain becomes obstructed, resulting in cerebral ischemia. This type of stroke accounts for approximately 87% of all strokes. Globally, IS leads to high mortality and poor prognosis and is associated with neuroinflammation and neuronal apoptosis. D-allose is a bio-substrate of glucose that is widely expressed in many plants. Our previous study showed that D-allose exerted neuroprotective effects against acute cerebral ischemic/reperfusion (I/R) injury by reducing neuroinflammation. Here, we aimed to clarify the beneficial effects D-allose in suppressing IS-induced neuroinflammation damage, cytotoxicity, neuronal apoptosis and neurological deficits and the underlying mechanism in vitro and in vivo. Methods: In vivo, an I/R model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 N mice, and D-allose was given by intraperitoneal injection within 5 min after reperfusion. In vitro, mouse hippocampal neuronal cells (HT-22) with oxygen–glucose deprivation and reperfusion (OGD/R) were established as a cell model of IS. Neurological scores, some cytokines, cytotoxicity and apoptosis in the brain and cell lines were measured. Moreover, Gal-3 short hairpin RNAs, lentiviruses and adeno-associated viruses were used to modulate Gal-3 expression in neurons in vitro and in vivo to reveal the molecular mechanism. Results: D-allose alleviated cytotoxicity, including cell viability, LDH release and apoptosis, in HT-22 cells after OGD/R, which also alleviated brain injury, as indicated by lesion volume, brain edema, neuronal apoptosis, and neurological functional deficits, in a mouse model of I/R. Moreover, D-allose decreased the release of inflammatory factors, such as IL-1β, IL-6 and TNF-α. Furthermore, the expression of Gal-3 was increased by I/R in wild-type mice and HT-22 cells, and this factor further bound to TLR4, as confirmed by three-dimensional structure prediction and Co-IP. Silencing the Gal-3 gene with shRNAs decreased the activation of TLR4 signaling and alleviated IS-induced neuroinflammation, apoptosis and brain injury. Importantly, the loss of Gal-3 enhanced the D-allose-mediated protection against I/R-induced HT-22 cell injury, inflammatory insults and apoptosis, whereas activation of TLR4 by the selective agonist LPS increased the degree of neuronal injury and abolished the protective effects of D-allose. Conclusions: In summary, D-allose plays a crucial role in inhibiting inflammation after IS by suppressing Gal-3/TLR4/PI3K/AKT signaling pathway in vitro and in vivo. [ABSTRACT FROM AUTHOR]

d -Allose is an aldohexose of the C3-epimer of d -glucose, existing in very small amounts in nature, called a rare sugar. The operon responsible for d -allose metabolism, the allose operon, was found in several bacteria, which consists of seven genes: alsR, alsB, alsA, alsC, alsE, alsK , and rpiB. To understand the biological implication of the allose operon utilizing a rare sugar of d -allose as a carbon source, it is important to clarify whether the allose operon functions specifically for d -allose or also functions for other ligands. It was proposed that the allose operon can function for d -ribose, which is essential as a component of nucleotides and abundant in nature. Allose-binding protein, AlsB, coded in the allose operon, is thought to capture a ligand outside the cell, and is expected to show high affinity for the specific ligand. X-ray structure determinations of Enterobacter cloacae AlsB (EtcAlsB) in ligand-free form, and in complexes with d -allose, d -ribose, and d -allulose, and measurements of the thermal parameters of the complex formation using an isothermal titration calorimeter were performed. The results demonstrated that EtcAlsB has a unique recognition mechanism for high affinity to d -allose by changing its conformation from an open to a closed form depending on d -allose-binding, and that the binding of d -ribose to EtcAlsB could not induce a completely closed form but an intermediate form, explaining the low affinity for d -ribose. [Display omitted] • The rare sugar allose is an aldohexose exitsing in very small amounts in nature. • The allose operon, responsible for allose metabolism, was found in several bacteria. • Allose-binding protein coded in the allose operon captures a ligand outside the cell. • Structures of the protein in complexes with various monosaccharides were determined. • The protein has an unique recognition mechanism for high affinity to allose. [ABSTRACT FROM AUTHOR]

• Low temperature and acid, alkali and ultrasonic pretreatments reduce the crystallinity of cellulose. • Cellulose generates 50.69 % D-Allose under the action of Al-Fe nano-catalyst at 330 °C. • High value utilization of cellulose by pyrolysis and generation of high yield of D-Allose. This research has made significant advancements in the field of high-value bio-oil production, specifically focusing on the synthesis of the rare sugar D-Allose. Notably, synthesizing D-Allose through cellulose pyrolysis has long been challenging due to its high synthetic difficulty, which has limited related studies. By employing a one-pot synthesis approach using Al x -Fe y nano-catalysts prepared through a unique cellulose pretreatment method, this experiment successfully achieved efficient generation of D-Allose during rapid pyrolysis. Systematic experimentation demonstrated that at 330 °C with the Al 1 -Fe 5 nano-catalyst, the yield of D-Allose from cellulose pyrolysis reached an impressive 50.69 %, accompanied by a detection of 14.35 % furfural in the bio-oil. This breakthrough not only significantly contributes to the high-value utilization of bio-oil but also provides robust support for further development in this area. Simultaneously, the success of this research extends beyond high-value bio-oil utilization and makes a substantial impact on both the scientific community and industry. [Display omitted] [ABSTRACT FROM AUTHOR]

D-Ribose plays fundamental roles in all living organisms and has been applied in food, cosmetics, health care, and pharmaceutical sectors. At present, D-ribose is predominantly produced by microbial fermentation based on the pentose phosphate pathway (PPP). However, this method suffers from a long synthetic pathway, severe growth defect of the host cell, and carbon catabolite repression (CCR). According to the Izumoring strategy, D-ribose can be produced from D-xylose through only three steps. Being not involved in the growth defect or CCR, this shortcut route is promising to produce D-ribose efficiently. However, this route has never been demonstrated in engineering practice, which hinders its application. In this study, we stepwise demonstrated this route and screened out higher active enzymes for each step. The first D-ribose production from D-xylose through the Izumoring route was achieved. By stepwise enzyme dosage tuning and process optimization, 6.87 g/L D-ribose was produced from 40 g/L D-xylose. Feeding D-xylose further improved the D-ribose titer to 9.55 g/L. Finally, we tested the coproduction of D-ribose and D-allose from corn stalk hydrolysate using the route engineered herein. In conclusion, this study demonstrated a pentose Izumoring route, complemented the engineering practices of the Izumoring strategy, paved the way to produce D-ribose from D-xylose, and provided an approach to comprehensively utilize the lignocellulosic sugars.

Two new glycosides of methyl everninate, rhodomollosides A (1) and B (2), were isolated from the aerial parts of a medicinal plant Rhododendron molle. The structures of 1 and 2 were elucidated on the basis of detailed spectroscopic analyses as well as HPLC analyses for thiazolidine derivatives of their sugar moieties. The sugar moiety of rhodomolloside A (1) was elucidated to be a rare monosaccharide, D-allose, while rhodomolloside B (2) was assigned as a D-glucoside of methyl everninate. Furthermore, they were evaluated for their cytotoxicity against RAW264.7 cells, and for their inhibitory effects with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW 264.7 cells model. [ABSTRACT FROM AUTHOR]

l -Rhamnose isomerase (l -RhI) catalyzes rare sugar isomerization between aldoses and ketoses. In an attempt to alter the substrate specificity of Thermoanaerobacterium saccharolyticus NTOU1 l -RhI (Ts RhI), residue Ile102 was changed to other polar or charged amino acid residues by site-directed mutagenesis. The results of activity-screening using different substrates indicate that I102N, I102Q, and I102R Ts RhIs can increase the preference against d -allose in comparison with the wild-type enzyme. The catalytic efficiencies of the purified I102N, I102Q, and I102R Ts RhIs against d -allose are 148 %, 277 %, and 191 %, respectively, of that of wild-type enzyme, while those against l -rhamnose are 100 %, 167 % and 87 %, respectively. Mutant I102N, I102Q, and I102R Ts RhIs were noted to have the altered substrate specificity, and I102Q Ts RhI has the highest catalytic efficiency against d -allose presumably through the formation of an additional hydrogen bond with d -allose. The purified wild-type and mutant Ts RhIs were further used to produce d -allose from 100 g/L d -fructose in the presence of d -allulose 3-epimerase, and the yields can reach as high as 22 % d -allulose and 12 % d -allose upon equilibrium. I102Q Ts RhI takes only around half of the time to reach the same 12 % d -allose yield, suggesting that this mutant enzyme has a potential to be applied in d -allose production. • Residue Ile102 of Ts RhI was changed to other polar or charged residues. • Mutant I102N, I102Q, and I102R Ts RhIs have the altered substrate specificity. • I102Q Ts RhI might form an additional hydrogen bond with d -allose. • I102Q Ts RhI takes around half time to reach equilibrium for d -allose production. • I102Q Ts RhI has a potential to be used in d -allose production. [ABSTRACT FROM AUTHOR]

D-Allose is classified as a 'rare sugar,' i.e., part of the group of monosaccharides that are present in low quantities in the natural world. D-Allose has been demonstrated to exert many physiological functions. The effects of the rare sugars on immune responses are largely unexplored. Here, we investigated the physiological effects of D-allose on murine dendritic cells' cytokine production. When plasmacytoid dendritic cells (pDCs) were stimulated with a Toll-like receptor 7 (TLR7) ligand, a single-stranded RNA (ssRNA), or a TLR9 ligand, CpG DNA, in the medium containing D-allose, the productions of both interferon-alpha (IFN-α) and interleukin (IL)-12p40 were severely decreased. In contrast, a normal production of these cytokines was observed when pDCs were stimulated with other TLR7 ligands, an imidazoquinoline, or a guanosine analog. In contrast to the pDCs, conventional dendritic cells (cDCs) produced IL-12p40 and tumor necrosis factor-alpha (TNF-α) in response to an imidazoquinoline or CpG DNA even though D-allose was present in the medium. D-Allose did not induce pDC death, and not inhibit the endocytic uptake of fluorophore-labeled CpG DNA into pDCs. These results suggested that D-allose exerts its inhibitory effects after CpG DNA is internalized. We analyzed the TLR7/9 signal-induced activation of downstream signaling molecules in pDCs and observed that when pDCs were stimulated with a ssRNA or CpG DNA, the phosphorylation status of the MAPK family, which includes Erk1/2, JNK/SAPK, and p38 MAPK, was attenuated in the presence of D-allose compared to D-glucose controls. The stimulation of pDCs with an imidazoquinoline induced a strong phosphorylation of these MAPK family members even in the presence of D-allose. These findings reveal that D-allose can inhibit the cytokine production by pDCs stimulated with ssRNA or CpG DNA via an attenuation of the phosphorylation of MAPK family members. • D-allose has a selective inhibitory effect on cytokine production by pDCs. • Endocytosis of TLR ligand into pDCs was not inhibited in the presence of D-allose. • TLR signal-induced activation of MAPKs was attenuated in the presence of D-allose. [ABSTRACT FROM AUTHOR]

D-Allose, a C3 epimer of D-glucose, has potential to improve human health as a functional food. However, its effect on the intestinal environment remains unknown. Aged humans progressively express changes in the gut, some of which deleteriously affect gastrointestinal health. In this study, we profiled the intestinal microbiome in aged mice and analyzed organic acids produced by bacteria in cecum contents after long-term ingestion of D-allose. D-Allose did not significantly change organic acid concentration. However, long-term ingestion did significantly increase the relative abundance of Actinobacteria and reduce the relative abundance of Proteobacteria. These results suggest that oral D-allose improves the proportion of favorable intestinal flora in aged mice. D-Allose significantly decreased the relative abundance of Lachnospiraceae bacteria, but increased the relative abundance of Bacteroides acidifaciens and Akkermansia muciniphila. Thus, D-allose might serve as a nutraceutical capable of improving the balance of gut microbiome during aging. [ABSTRACT FROM AUTHOR]

D-Allose is a rare natural sugar, which is attractive as a sweetener alternative to sugar because of its biological functions and low-calorie content. However, there is a lack of basic information regarding the use of D-allose as a food ingredient. In this study D-allose toxicity to ICR mice was investigated. The mice were treated with a single dose of D-allose (1,250, 2,500 or 5,000 mg/kg body weight). No organ injury was observed, nor any changes observed in the clinical sign, body weight and the blood serum chemistry. The approximate lethal dose was estimated to exceed 5,000 mg/kg in mice. These results suggest that D-allose is practically non-toxic to mice. [ABSTRACT FROM AUTHOR]

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viability and intracellular ROS elevation. Furthermore, oral administration of D-allose inhibited tumor growth without adverse effects (p < 0.05). Histopathological findings in tumor tissues showed that D-allose decreased the nuclear fission rate from 4.1 to 1.1% (p = 0.004). Oral administration of D-allose suppressed BC growth in a preclinical mouse model, possibly through up-regulation of TXNIP expression followed by an increase in intracellular ROS. Therefore, D-allose is a potential therapeutic compound for the treatment of BC. [ABSTRACT FROM AUTHOR]

A putative l-rhamnose isomerase (l-RI) gene from Paenibacillus baekrokdamisoli was expressed as a recombinant enzyme in Escherichia coli BL21(DE3) and characterized as a producer of d-allose from d-allulose. Recombinant l-RI from P. baekrokdamisoli was homogeneously purified on SDS-PAGE with a 46 kDa molecular mass and specific activity of 1.27 U/mg by His-Trap affinity chromatography. The enzyme was estimated to be a tetramer in enzyme active form because its molecular mass was determined to be approximately 190 kDa by Gelfiltration chromatography. In the isomerization reaction between d-allose and d-allulose, recombinant l-RI exhibited the highest activity at pH 8.0 and 60°C in the presence of 0.5 mM Mn2+. The half-lives of the enzyme at 50, 55, 60, 65, 70, and 75°C were 417, 57, 27, 20, 3.3, and 0.2 h, respectively. The Michaelis-Menten constants (Km), turnover numbers (kcat), and catalytic efficiencies (kcat/Km) of the enzyme for d-allose and d-allulose were 33 mM, 13.79 s−1, and 0.4 mM−1s−1 and 45.24 mM, 6.58 s−1, and 0.14 mM−1s−1, respectively. The enzyme showed isomerization activity for aldoses with right-handed configuration of hydroxyl group at the C-2 and C-3 positions, such as l-mannose, l-lyxose, d-gulose, d-allose, and d-ribose. During production of d-allose from d-allulose, the enzyme produced 125 g/L of d-allose from 500 g/L of d-allulose in 3 h with 41.6 g/L/h productivity with 104 U/mL enzyme. We first reported the l-RI from the Paenibacillus genus, and the results suggested that the P. baekrokdamisolil-RI could be applied as a d-allose producer. [ABSTRACT FROM AUTHOR]

Chemical investigation of the stems and leaves of Passiflora edulis Sims led to the isolation of a pair of phenylethanoid glycosides (1, 2), two benzyl alcohol glycosides (3, 4), and two cyanogenic glycosides (5, 6). Compounds 1 and 2 were an inseparable mixture in a 1:2 ratio. The structures were identified by spectroscopic analysis and comparison with literature data. Compound 1 was a new phenylethanoid alloside, and compound 2 was found in this plant for the first time. [ABSTRACT FROM AUTHOR]

The hallmark of pathological cardiac hypertrophy is the decline in myocardial contractility caused by an energy deficit resulting from metabolic abnormalities, particularly those related to glucose metabolism. Here, we aim to explore whether D-Allose, a rare sugar that utilizes the same transporters as glucose, may restore metabolic equilibrium and reverse cardiac hypertrophy. Isolated neonatal rat cardiomyocytes were stimulated with phenylephrine and treated with D-Allose simultaneously for 48 h. D-Allose treatment resulted in a pronounced reduction in cardiomyocyte size and cardiac remodelling markers accompanied with a dramatic reduction in the level of intracellular glucose in phenylephrine-stimulated cells. The metabolic flux analysis provided further insights revealing that D-Allose exerted a remarkable inhibition of glycolysis as well as glycolytic capacity. Furthermore, in mice subjected to a 14-day continuous infusion of isoproterenol (ISO) to induce cardiac hypertrophy, D-Allose treatment via drinking water notably reduced ISO-induced cardiac hypertrophy and remodelling markers, with minimal effects on ventricular wall thickness observed in echocardiographic analyses. These findings indicate that D-Allose has the ability to attenuate the progression of cardiomyocyte hypertrophy by decreasing intracellular glucose flux and inhibiting glycolysis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

d-Allose is the C3 epimer of d-glucose and has been reported to have beneficial health effects. The transporter mediating intestinal transport of d-allose is unknown. We examined whether d-allose is absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via glucose transporter type 5 (GLUT5) using rats. For examination of absorption via SGLT1, KGA-2727, an SGLT1-specific inhibitor, and d-allose were orally administered. KGA-2727 blocked the increase of plasma d-allose levels and suppressed them throughout the experiment (0–180 min), whereas without KGA-2727, the plasma d-allose levels peaked at around 60–90 min. For examination of absorption via GLUT5, rats were fed a high-fructose diet for 3weeks to increase the abundance and activity of GLUT5 in the small intestine. High-fructose diet-fed rats did not exhibit significant changes in the plasma d-allose levels compared to control rats fed a high-glucose diet. These results indicate that SGLT1 but not GLUT5 mediates the intestinal absorption of d-allose.

Abstract Background D-allose was promising in the protection of ischemia/reperfusion (I/R) injury. We intended to investigate the function of D-allose in skin flap of rat followed by the injury of I/R and whether ERK signal pathway was involved in. Methods The back flap of Wistar rats was picked up with a vascular bundle of the lateral chest wall. I/R model was made by the venous clamp for 6 h. Rats received D-allose and PD-98059, the inhibitor of ERK1/2, 30 min before modeling. Morphology of tissue was observed by HE staining. Nitric oxide (NO), myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels in skin flap were determined by ELISA kits. mRNA and protein levels were determined by qPCR and Western blot respectively. Results D-allose alleviated the condition of pathological changes and raised the survival rate of skin flap injured by I/R. Moreover, D-allose suppressed NO, MPO and MDA while elevated SOD levels during I/R status. Furthermore, D-allose decreased MCP-1, TNF-α, IL-1β and IL-6 levels in skin flap injured by I/R. In addition, D-allose inhibited MKP-1 expression and activated ERK1/2 pathway in skin flap injured by I/R. PD-98059 partially counteracted D-allose effects on I/R injury. Conclusions D-allose exerted its protective function via inhibiting MKP-1expression and further activated ERK1/2 pathway to suppress the progress of oxidative stress, inflammation and necrosis, contributing to the survival of skin flap injured by I/R. Thus, D-allose was promising in the transplantation of skin flap.

Rare sugars are regarded as functional biological materials due to their potential applications as low-calorie sweeteners, antioxidants, nucleoside analogs, and immunosuppressants. D-Allose is a rare sugar that has attracted substantial attention in recent years, owing to its pharmaceutical activities, but it is still not widely available. To address this limitation, we continuously produced D-allose from D-allulose using a packed bed reactor with commercial glucose isomerase (Sweetzyme IT). The optimal conditions for D-allose production were determined to be pH 8.0 and 60°C, with 500 g/L D-allulose as a substrate at a dilution rate of 0.24/h. Using these optimum conditions, the commercial glucose isomerase produced an average of 150 g/L D-allose over 20 days, with a productivity of 36 g/L/h and a conversion yield of 30%. This is the first report of the successful continuous production of D-allose from D-allulose by commercial glucose isomerase using a packed bed reactor, which can potentially provide a continuous production system for industrial applications of D-allose.

D-allose, a rare sugar with anti-oxidant, anti-inflammatory, anti-cancer, immunosuppressing and other physiological functions, has become a research hotspot in recent years. This paper describes the physical and chemical properties, synthesis methods, metabolism, physiological functions, and applications of D-allose, aiming to promote the functional development of D-allose and facilitate the application of D-allose in the food field and clinical treatment.

D-Allose and its derivatives play important roles in the field of health care and food nutrition. Pure and well-defined D-allose derivatives can facilitate the elucidation of their structure-activity relationship as an essential step for drug design. The Lattrell-Dax epimerization, refers to the triflate inversion using nitrite reagent, is known as valuable method for the synthesis of rare D-allose derivatives. Here, the influence of protecting group patterns on the transformation efficiency of D-glucose derivatives into synthetically useful D-alloses and D-allosamines via the Lattrell-Dax epimerization was studied. For C3 epimerization of D-glucose derivatives bearing O 2-acyl group, an anomeric configuration-dependent acyl migration from O 2 to O 3 was found. In addition, a neighbouring group participation effect-mediated S N 1 nucleophilic substitution of the D-glucosamine bearing C2 trichloroacetamido (TCA) group in the Lattrell-Dax epimerization was dependent upon anomeric configuration. Thus, the effect of anomeric configuration on the Lattrell-Dax epimerization of D-glucose suggests that β -D-glucosides with low steric hindrance at C2 should be better substrates for the synthesis of D-allose derivatives. Significantly, the efficient synthesis of the orthogonally protected D-allose 13 and D-allosamine 18 will serve well for further assembly of complex glycans. [ABSTRACT FROM AUTHOR]

Citrus fruits are rich sources of different phytochemicals for human health due to their high anti-oxidant capacity. However, the anti-aging effect of citrus fruits has not been well understood. In this study, methanol extracts taken at various developmental stages from tissues of Citrus unshiu was used to investigate its anti-aging effect by an elastase/collagenase inhibition assay, and a gas chromatography-mass spectrometry (GC-MS) analysis was carried out to identify the potential anti-aging compositions. The elastase/collagenase inhibitory activity was greatest in the flesh of immature green fruit (i.e., early July flesh (EJF)), and four candidate compounds were selected by GC-MS and evaluated by a collagenase inhibition assay. Three of the four candidate compounds (heptadecanoic acid, D-allose, and 5-hydroxymethyl-2-furaldehyde (HMF)) showed anti-aging activity, and the activity was highest in heptadecanoic acid, followed by D-allose and HMF. The total phenolic content (TPC), total flavonoid content (TFC), and anti-oxidant activity (DPPH and ferric reducing anti-oxidant power (FRAP) assay) were also investigated. Interestingly, the patterns of the total phenolic/flavonoid content and the anti-oxidant activity were different from that of the elastase/collagenase inhibitory activity. Flowers had the most anti-oxidant activity followed by immature fruit, and the fruit peels had more anti-oxidant activity than its flesh at all stages of development. This study demonstrated that the flesh of immature fruit and flowers of C. unshiu could be sources of anti-aging and anti-oxidant agents for human health, respectively. [ABSTRACT FROM AUTHOR]

d-Allose is a rare sugar, can be used as an ingredient in a range of foods and dietary supplements, has alimentary activities, especially excellent anti-cancer effects and used in assisting cancer chemotherapy and radiotherapy, etc. To develop a simple and low-cost process for d-allose production, a one-pot enzymatic process using the substrate of d-fructose, and the recombinant enzymes of d-psicose 3-epimerase (DPE) and l-rhamnose isomerase (l-RhI) was developed. These enzymes were cloned from Ruminococcus sp. and B. subtilis, respectively, successfully expressed in E. coli, extracted and immobilized using anion exchange resin and amino resin, respectively. The mass ratio of d-fructose, d-psicose and d-allose was 6.6:2.4:1.0 when the reaction reached equilibrium after 5 h of reaction. Using the low-cost substrate of d-fructose, the reusable immobilized enzymes and the one-pot reaction, the production process is simplified and the production cost is decreased. In addition, to simplify the enzyme extraction and immobilization processes, new methods for enzyme capture and immobilization were developed especially for DPE immobilization. This is the first report for one-pot d-allose production using immobilized l-RhI and DPE. [ABSTRACT FROM AUTHOR]

Background/aim: The present study investigated the anticancer effects of intraperitoneally administered D-allose in in vivo models of head and neck cancer cell lines., Materials and Methods: To assess the direct effects of D-allose, its dynamics in blood and tumor tissues were examined., Results: D-allose was detected in blood and tumor tissues 10 min after its intraperitoneal administration and then gradually decreased. In vivo experiments revealed that radiation plus D-allose was more effective than either treatment alone. Thioredoxin-interacting protein (TXNIP) mRNA over-expression was detected after the addition of D-allose in in vitro and in vivo experiments. D-allose inhibited cell growth, which was associated with decreases in glycolysis and intracellular ATP levels and the prolonged activation of AMPK. The phosphorylation of p38-MAPK was also observed early after the administration of D-allose and was followed by the activation of AMPK and up-regulated expression of TXNIP in both in vitro and in vivo experiments., Conclusion: Systemically administered D-allose appears to exert antitumor effects. Further studies are needed to clarify the appropriate dosage and timing of the administration of D-allose and its combination with other metabolic agents., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

2-Deoxy-d-glucose (2DG) induces anticancer effects through glycolytic inhibition but it may raise the risk of arrhythmia. The rare monosaccharide d-allose also has anticancer properties, but its cardiac effects are unknown. We examined the effects of d-allose on adenosine triphosphate (ATP) production in neonatal rat cardiomyocytes. We showed that 25 mM d-allose selectively reduced glycolytic ATP, but had minimal impact on mitochondrial ATP, while 1 mM 2DG strongly inhibited both. Furthermore, d-allose had less impact on cell viability and was less cytotoxic than 2DG; neither compound caused apoptosis. Thus, d-allose selectively diminished glycolytic ATP production with no apparent effects on cardiomyocytes., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Peritoneal dialysis (PD) is a crucial dialysis method for treating end-stage kidney disease. However, its use is restricted due to high glucose-induced peritoneal injury and hyperglycaemia, particularly in patients with diabetes mellitus. In this study, we investigated whether partially replacing d-glucose with the rare sugar d-allose could ameliorate peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid (PDF)., Methods: Rat peritoneal mesothelial cells (RPMCs) were exposed to a medium containing d-glucose or d-glucose partially replaced with different concentrations of d-allose. Cell viability, oxidative stress and cytokine production were evaluated. Sprague-Dawley (SD) rats were administrated saline, a PDF containing 4% d-glucose (PDF-G4.0%) or a PDF containing 3.6% d-glucose and 0.4% d-allose (PDF-G3.6%/A0.4%) once a day for 4 weeks. Peritoneal injury and PD efficiency were assessed using immuno-histological staining and peritoneal equilibration test, respectively. Blood glucose levels were measured over 120 min following a single injection of saline or PDFs to 24-h fasted SD rats., Results: In RPMCs, the partial replacement of d-glucose with d-allose increased cell viability and decreased oxidative stress and cytokine production compared to d-glucose alone. Despite the PDF-G3.6%/A0.4% having a lower d-glucose concentration compared to PDF-G4.0%, there were no significant changes in osmolality. When administered to SD rats, the PDF-G3.6%/A0.4% suppressed the elevation of peritoneal thickness and blood d-glucose levels induced by PDF-G4.0%, without impacting PD efficiency., Conclusions: Partial replacement of d-glucose with d-allose ameliorated peritoneal injury and hyperglycaemia induced by high concentration of d-glucose in PDF, indicating that d-allose could be a potential treatment option in PD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Two fluorine-18-labeled analogues, 3-deoxy-3-[18F]fluoro-D-allose (3-[18F]FDA) and 6-deoxy-6-[18F]fluoro-D-allose (6-[18F]FDA), were synthesized and their potentials of diagnostic property were characterized.Methods: In vitro rat red blood cell (RBC) transport and phosphorylation by yeast hexokinase were evaluated in comparison with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). The rate of protein binding in pooled human serum was measured by an ultrafiltration method. In vivo metabolite analysis in mice was also performed. Biodistribution, urine excretion, and in vivo renal kinetics in mice were compared with 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS).Results: Rat RBC uptake of 3- and 6-[18F]FDA (7.8 ± 2.5%ID and 10.2 ± 4.8%ID, respectively) was significantly lower than that of [18F]FDG (44.7 ± 8.7%ID). RBC uptake of 3-[18F]FDA was inhibited by D-glucose (30%) and cytochalasin B (40%), indicating the involvement of GLUT1-dependent transport. In contrast, 6-[18F]FDA transport was not inhibited by D-glucose and cytochalasin B. 3- and 6-[18F]FDA were not phosphorylated by yeast hexokinase under the conditions that result in 60% conversion of [18F]FDG into [18F]FDG-6-phosphate within 30 min. Serum protein binding of 3- and 6-[18F]FDA was negligible. Metabolic transformation of both tracers was not detected in plasma and urine at 30 min after injection. The highest tissue uptake of both tracers was observed in kidneys. Heart and brain uptake of both tracers was below blood levels throughout the biodistribution studies (until 120 min after injection). No significant uptake in the bone was observed, indicating the absence of de-fluorination in mice. In vivo PET imaging visualized rapid excretion of the administered 3- and 6-[18F]FDA from the kidneys, with minimal tracer accumulation in other organs. The urine excretion rate of 3-[18F]FDA was much lower than that of 6-[18F]FDA and [18F]FDS.Conclusions: 3- and 6-[18F]FDA might be unsatisfactory for tumor imaging. In contrast, these tracers demonstrated high levels of kidney uptake and excretion, low serum protein binding, and high metabolic stability as preferable properties for renal imaging. Notably, the urine excretion rate and kidney uptake kinetics of 6-[18F]FDA were comparable with those of the potential renal imaging agent [18F]FDS. Further validation studies in animal models are required to confirm the feasibility of 6-[18F]FDA as a functional renal imaging agent. [ABSTRACT FROM AUTHOR]

D-Allose and D-allulose are two important rare natural monosaccharides found in meager amounts. They are considered to be the ideal substitutes for table sugar (sucrose) for, their significantly lower calorie content with around 80 % and 70 % of the sweetness of sucrose, respectively. Additionally, both monosaccharides have gained much attention due to their remarkable physiological properties and excellent health benefits. Nevertheless, D-allose and D-allulose are rare in nature and difficult to produce by chemical methods. Consequently, scientists are exploring bioconversion methods to convert D-allulose into D-allose, with a key enzyme, L-rhamnose isomerase (L-RhIse), playing a remarkable role in this process. This review provides an in-depth analysis of the extractions, physiological functions and applications of D-allose from D-allulose. Specifically, it provides a detailed description of all documented L-RhIse, encompassing their biochemical properties including, pH, temperature, stabilities, half-lives, metal ion dependence, molecular weight, kinetic parameters, specific activities and specificities of the substrates, conversion ratio, crystal structure, catalytic mechanism as well as their wide-ranging applications across diverse fields. So far, L-RhIses have been discovered and characterized experimentally by numerous mesophilic and thermophilic bacteria. Furthermore, the crystal forms of L-RhIses from E. coli and Stutzerimonas/Pseudomonas stutzeri have been previously cracked, together with their catalytic mechanism. However, there is room for further exploration, particularly the molecular modification of L-RhIse for enhancing its catalytic performance and thermostability through the directed evolution or site-directed mutagenesis. • D-Allose and D-allulose are rare sugars and isomers of each other. • D-Allose and D-allulose have great importance in the field of food and pharmaceutical. • L-Rhamnose isomerase can catalyze various aldoses into their respective ketoses. • L-Rhamnose isomerase can produce high amount of D-allose by using D-allulose as a substrate. • L-Rhamnose isomerase can also catalyze the reversible isomerization between many other rare sugars. [ABSTRACT FROM AUTHOR]

Citrus fruits are rich sources of different phytochemicals for human health due to their high anti-oxidant capacity. However, the anti-aging effect of citrus fruits has not been well understood. In this study, methanol extracts taken at various developmental stages from tissues of Citrus unshiu was used to investigate its anti-aging effect by an elastase/collagenase inhibition assay, and a gas chromatography-mass spectrometry (GC-MS) analysis was carried out to identify the potential anti-aging compositions. The elastase/collagenase inhibitory activity was greatest in the flesh of immature green fruit (i.e., early July flesh (EJF)), and four candidate compounds were selected by GC-MS and evaluated by a collagenase inhibition assay. Three of the four candidate compounds (heptadecanoic acid, D-allose, and 5-hydroxymethyl-2-furaldehyde (HMF)) showed anti-aging activity, and the activity was highest in heptadecanoic acid, followed by D-allose and HMF. The total phenolic content (TPC), total flavonoid content (TFC), and anti-oxidant activity (DPPH and ferric reducing anti-oxidant power (FRAP) assay) were also investigated. Interestingly, the patterns of the total phenolic/flavonoid content and the anti-oxidant activity were different from that of the elastase/collagenase inhibitory activity. Flowers had the most anti-oxidant activity followed by immature fruit, and the fruit peels had more anti-oxidant activity than its flesh at all stages of development. This study demonstrated that the flesh of immature fruit and flowers of C. unshiu could be sources of anti-aging and anti-oxidant agents for human health, respectively.

Listeria monocytogenes, an important food-borne pathogen, causes listeriosis and is widely distributed in many different environments. In a previous study, we developed a novel enrichment broth containing D-allose that allows better isolation of L. monocytogenes from samples. However, the mechanism of D-allose utilization by L. monocytogenes remains unclear. In the present study, we determined the metabolism of D-allose in L. monocytogenes and found that lineage II strains of L. monocytogenes can utilize D-allose as the sole carbon source for growth, but lineage I and III strains cannot. Transcriptome analysis and sequence alignment identified six genes (lmo0734 to 0739) possibly related to D-allose metabolism that are only present in the genomes of lineage II strains. Recombinant strain ICDC-LM188 containing these genes showed utilization of D-allose by growth assays and Biolog phenotype microarrays. Moreover, lmo0734 to 0736 were verified to be essential for D-allose metabolism, lmo0737 and 0738 affected the growth rate of L. monocytogenes in D-allose medium, while lmo0739 was dispensable in the metabolism of D-allose in L. monocytogenes. This is the first study to identify the genes related to D-allose metabolism in L. monocytogenes, and their distribution in lineage II strains. Our study preliminarily determined the effects of these genes on the growth of L. monocytogenes, which will benefit the isolation and epidemiological research of L. monocytogenes.

The present study was designed to evaluate the effect of one rare sugar, D‑allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D‑allose in an in vivo model of head and neck cancer. Results indicated that D‑allose did not inhibit the growth of normal human fibroblasts TIG‑1 cells, and no apoptotic changes were observed after D‑allose and D‑glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG‑1 cells after D‑allose treatment increased by 2‑fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74‑fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D‑allose treatment. Combined multiple treatments with docetaxel, radiation and D‑allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor‑α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D‑allose administration. Thus, the present findings suggest that D‑allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is characterized by excess lipid accumulation and inflammation in hepatocytes. In this study, to provide insight into the preventive effects of D-allose, a rare sugar, on the onset of NASH, we designed animal experiments using male STAM mice treated with streptozotocin and fed a high-fat diet (HFD). Experiments were initiated when the mice reached 5 weeks of age and lasted 3 weeks. After the 3-week protocol, mice fed the HFD containing D-allose exhibited significantly decreased serum alanine aminotransferase levels, hepatic lipid accumulation and inflammation, and improved nonalcoholic fatty liver disease activity score compared to mice fed HFD without D-allose (p < 0.05). Further, hepatic mRNA expression of sterol regulatory element binding protein-1 (Srebp-1) and monocyte chemotactic protein-1 (Mcp-1) was lower in mice fed D-allose. These results suggested that D-allose prevented NASH by blocking hepatic lipid accumulation and progressive inflammation. [ABSTRACT FROM AUTHOR]

D -Allose is a rare cis-caprose with a wide range of physiological functions, which has a wide range of applications in medicine, food, and other industries. L -Rhamnose isomerase (L -Rhi) is the earliest enzyme found to catalyze the production of D -allose from D -psicose. This catalyst has a high conversion rate, but its specificity for substrates is limited; thus, it cannot fulfill the requirements of industrial production of D -allose. In this study, L -Rhi derived from Bacillus subtilis was employed as the research subject, and D -psicose as the conversion substrate. Two mutant libraries were constructed through alanine scanning, saturation mutation, and rational design based on the analysis of the secondary structure, tertiary structure, and interactions with ligands of the enzyme. The yield of D -allose produced by these mutants was assessed; it was found that the conversion rate of mutant D325M to D -allose was increased by 55.73 %, and the D325S improved by 15.34 %, while mutant W184H increased by 10.37 % at 55 °C, respectively. According to modeling analysis, manganese (Mn2+) had no significant effect on the production of D -psicose from D -psicose by L -Rhi. The results of molecular dynamics simulation demonstrated that the mutants W184H, D325M, and D325S had more stable protein structures while binding with the substrate D -psicose, as evidenced by its root mean square deviation (RMSD), root mean square fluctuation (RMSF), and binding free energy values. It was more conducive to binding D -psicose and facilitating its conversion to D -allose, providing the basis for the production of D -allose. • The yield of D -allose generated by positive L -Rhi mutants increased by 55.73 %, 15.34 %, and 10.37 %, respectively. • There was no metal ion binding and the binding position of the substrate had altered in the mutants D325M and D325S. • The optimum temperature of the mutants decreased and ligand-enzyme complexes were more stable. [ABSTRACT FROM AUTHOR]

d-Allose is a low-calorie rare sugar with great application potential in the food and pharmaceutical industries. The production of d-allose has been accomplished using l-rhamnose isomerase (L-RI), but concomitantly increasing the enzyme's stability and activity remains challenging. Here, we rationally engineered an L-RI from Clostridium stercorarium to enhance its stability by comprehensive computation-aided redesign of its flexible regions, which were successively identified using molecular dynamics simulations. The resulting combinatorial mutant M2-4 exhibited a 5.7-fold increased half-life at 75 °C while also exhibiting improved catalytic efficiency. Especially, by combining structure modeling and multiple sequence alignment, we identified an α0 region that was universal in the L-RI family and likely acted as a "helix-breaker". Truncating this region is crucial for improving the thermostability of related enzymes. Our work provides a significantly stable biocatalyst with potential for the industrial production of d-allose.

Our early experiments confirmed that D-allose was closely involved in the blood brain barrier (BBB) protection from ischemia reperfusion (IR) injury, but the regulatory mechanism is not fully defined. In this study, we aimed to investigate the role of D-allose in the protection of BBB integrity and the relevant mechanisms involved in the mice model of middle cerebral artery occlusion and reperfusion (MCAO/Rep). D-allose was intravenously injected via a tail vein (0.2 mg/g and 0.4 mg/g, 1 h before ischemia), GW9662 was intraperitoneal injected to the mice (4 mg/kg) before inducing ischemia 24 h. Pretreatment with D-allose ameliorated the neurological deficits, infarct volume and brain edema in brains of MCAO/Rep mice. D-allose inhibited cell apoptosis in the mice model of MCAO/Rep. We observed that D-allose remarkably decreased BBB permeability and prevented the reduction of ZO-1, Occludin and Claudin-5 in mice brains with MCAO/Rep injury. D-allose also repressed the levels of TNF-α, NF-κB, interleukin (IL)-1β and IL-8 in inflammatory responses. The increases of intercellular adhesion molecular-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and CD11b/CD18 were significantly inhibited by D-allose during the MCAO/Rep injury. And D-allose decreased the L-selectin and P-selectin levels after MCAO/Rep. Moreover, D-allose induced up-regulation of peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of TNF-α and NF-κB after MCAO/Rep, which were abolished by utilization of GW9662. In conclusion, we provided evidences that D-allose may has therapeutic potential against brain IR injury through attenuating BBB disruption and the inflammatory response via PPARγ-dependent regulation of NF-κB. [ABSTRACT FROM AUTHOR]

l-Rhamnose isomerase (L-RI, EC 5.3.1.14), catalyzing the isomerization between l-rhamnose and l-rhamnulose, plays an important role in microbial l-rhamnose metabolism and thus occurs in a wide range of microorganisms. It attracts more and more attention because of its broad substrate specificity and its great potential in enzymatic production of various rare sugars. In this article, the enzymatic properties of various reported L-RIs were compared in detail, and their applications in the production of l-rhamnulose and various rare sugars including d-allose, d-gulose, l-lyxose, l-mannose, l-talose, and l-galactose were also reviewed. [ABSTRACT FROM AUTHOR]

[Display omitted] • d -allose significantly increased the cell viability of RBMECs after H/R. • d -allose inhibits the expression of the ERS marker molecule eIF2α. • d -allose inhibits the activation of the UPR pathway. Ischemic stroke is an acute brain disease with a high mortality rate. Currently, the only effective method is to restore the blood supply. But the inflammation and oxidative stress induced by this approach can damage the integrity of the endothelial system, which hampers the patient's outcome. d -allose has the biological activity to protect against ischemia–reperfusion injury, however, the underlying mechanism remains unclear. Here, brain microvascular endothelial cells (RBMECs) were used as the study material to establish an IR-injury model. Cell viability of RBMECs was suppressed after hypoxia/reoxygenation (H/R) treatment and significantly increased after d -allose supplementation. RNAseq results showed 180 differentially expressed genes (DEGs) between the therapy group (H/R + Dal) and the model group (H/R), of which 151 DEGs were restored to control levels by d -allose. Enrichment analysis revealed that DEGs were mainly involved in protein processing in endoplasmic reticulum. 6 DEGs in the unfolded protein response (UPR) pathway were verified by qRT-PCR. All of them were significantly down-regulated by d -allose, indicating that endoplasmic reticulum stress (ERS) was relieved. In addition, d -allose significantly inhibited the phosphorylation level of eIF2α, a marker of ERS. The downstream molecules of Phosphorylation of eIF2α, Gadd45a and Chac1, which trigger cycle arrest and apoptosis, respectively, were also significantly inhibited by d -allose. Thus, we conclude that d -allose inhibits the UPR pathway, attenuates eIF2α phosphorylation and ERS, restores the cell cycle, inhibits apoptosis, and thus enhances endothelial cell tolerance to H/R injury. [ABSTRACT FROM AUTHOR]

Glucose is a major energy source for mammalian cells and is transported into cells via cell-specific expression of various glucose transporters (GLUTs). Especially, cancer cells require massive amounts of glucose as an energy source for their dysregulated growth and thus over-express GLUTs. D-allose, a C-3 epimer of D-glucose, is one of rare sugars that exist in small quantities in nature. We have shown that D-allose induces the tumor suppressor gene coding for thioredoxin interacting protein (TXNIP) and inhibits cancer cell growth by G1 cell cycle arrest. It has also been reported that GLUTs including GLUT1 are overexpressed in many cancer cell lines, which may contribute to larger glucose utilization. Since D-allose suppresses the growth of cancer cells through the upregulation of TXNIP expression, our present study focused on whether D-allose down-regulates GLUT1 expression via TXNIP expression and thus suppresses cancer cell growth. Western blot and real-time PCR analyses revealed that D-allose significantly induced TXNIP expression and inhibited GLUT1 expression in a dose-dependent manner in three human cancer cell lines: hepatocellular carcinoma (HuH-7), Caucasian breast adenocarcinoma (MDA-MB-231), and neuroblastoma (SH-SY5Y). In these cell lines, D-allose treatment inhibited cell growth. Importantly, D-allose treatment decreased glucose uptake, as measured by the uptake of 2-deoxy D-glucose. Moreover, the reporter assays showed that D-allose decreased the expression of luciferase through the hypoxia response element present in the tested promoter region. These results suggest that D-allose may cause the inhibition of cancer growth by reducing both GLUT1 expression and glucose uptake. [ABSTRACT FROM AUTHOR]

Background: Pretransplant restoration of islets damaged during isolation remains to be solved. In this study, we examined the effect of D‐allose on islets isolated from rat pancreata prior to islet transplantation. Methods: Rat islets isolated from fresh pancreata were cultured overnight in Roswell Park Memorial Institute 1640 solution in the absence (group 1) or presence (group 2) of D‐allose. Then we assessed stimulation index of insulin, and cure rate after islet transplantation to diabetic nude mice. We also measured malondialdehyde level and caspase 3 activity of islets after the overnight culture for assessment of the oxidative stress and the apoptosis. Results: D‐allose significantly improved insulin secretion of islets. The stimulation index in group 2 was significantly higher than in group 1. Cure rate after transplantation in group 2 was higher than in group 1 especially in the first week. The malondialdehyde level in group 2 was significantly lower than in group 1. But the caspase 3 activities in both groups did not differ. Conclusions: D‐allose treatment of isolated islet culture prior to transplantation restored islet function and increased successful transplant rate. The results of this study suggested that D‐allose improved function of damaged islets through its anti‐oxidative activity. Highlight Islet recovery is of great importance for successful transplantation. The rare sugar D‐allose, a glucose isomer, dissolved in culture medium, increased the cure rate after islet transplantation to diabetic nude mice. Kashiwagi and colleagues conclude that D‐allose repaired islet damage from ischemia‐reperfusion injury in isolation steps through its anti‐oxidative activity. [ABSTRACT FROM AUTHOR]