Oral preparation of hyaluronic acid, chondroitin sulfate, N-acetylglucosamine, and vitamin C improves sexual and urinary symptoms in participants with recurrent urinary tract infections: a randomized crossover trial.

BACKGROUND: Intravesical instillation of hyaluronic acid (HA) has been associated with reduced sexual dysfunction in participants with recurrent urinary tract infections (rUTIs), but the efficacy of an oral treatment has never been investigated. AIM: To investigate the efficacy of an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C in improving sexual and urinary symptoms in a cohort of reproductive-age participants with rUTI. METHODS: In a monocentric randomized crossover pilot trial, participants with rUTI who were referred to our institute between March 2022 and April 2023 were randomized 1:1 in 2 groups: intervention vs control. All participants had an oral preparation of cranberry, D-mannose, propolis extract, turmeric, and Boswellia twice a day for 3 months. The intervention group also included an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C once a day for 3 months. Crossover of treatment occurred at 3 months for an additional 3 months. At baseline and 3 and 6 months, participants were evaluated clinically and with the International Prostate Symptom Score (IPSS) and Female Sexual Function Index (FSFI). Descriptive statistics and logistic regression models tested the impact of the intervention on urinary and sexual symptoms at each follow-up assessment. OUTCOMES: Improvement in sexual and urinary symptoms as measured by the FSFI and IPSS. RESULTS: Overall, 27 (54%) participants had an FSFI score <26.5 at enrollment. At 3 months, FSFI scores were higher in the intervention group vs control (P < .001), but IPSS scores were lower (P = .03). After crossover of treatment, FSFI and IPSS scores remained stable in the intervention group. However, after crossover, the control group showed a significant improvement in IPSS and FSFI scores (all P < .01) vs the 3-month assessment. At last follow-up, urinary and sexual symptoms were comparable between groups. In logistic regression analyses, the intervention group was associated with early improvement in sexual symptoms (odds ratio, 3.9; P = .04) and urinary symptoms (odds ratio, 5.1; P = .01) after accounting for clinical confounders. CLINICAL IMPLICATIONS: Combination treatment with HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C is effective if started immediately or even after a few months from symptoms in participants with rUTI. STRENGTHS AND LIMITATIONS: The main limitation is the lack of long-term follow-up. CONCLUSION: The oral formulation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C could be an effective therapy against urinary and sexual distress in participants with rUTI (NCT06268483; ClinicalTrials.gov).

MicroSPECT Imaging-Guided Treatment of Idiopathic Pulmonary Fibrosis in Mice with a Vimentin-Targeting 99mTc-Labeled N-Acetylglucosamine-Polyethyleneimine.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. 99mTc-labeled N-acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with 99mTc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of 99mTc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of 99mTc-NAG-PEI in the NAG-PEI/TGF-ß1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of 99mTc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.

Serum Antibody Activity against Poly-N-Acetyl Glucosamine (PNAG), but Not PNAG Vaccination Status, Is Associated with Protecting Newborn Foals against Intrabronchial Infection with Rhodococcus equi.

Rhodococcus equi is a prevalent cause of pneumonia in foals worldwide. Our laboratory has demonstrated that vaccination against the surface polysaccharide ß-1→6-poly-N-acetylglucosamine (PNAG) protects foals against intrabronchial infection with R. equi when challenged at age 28 days. However, it is important that the efficacy of this vaccine be evaluated in foals when they are infected at an earlier age, because foals are naturally exposed to virulent R. equi in their environment from birth and because susceptibility is inversely related to age in foals. Using a randomized, blind experimental design, we evaluated whether maternal vaccination against PNAG protected foals against intrabronchial infection with R. equi 6 days after birth. Vaccination of mares per se did not significantly reduce the incidence of pneumonia in foals; however, activities of antibody against PNAG or for deposition of complement component 1q onto PNAG was significantly (P < 0.05) higher among foals that did not develop pneumonia than among foals that developed pneumonia. Results differed between years, with evidence of protection during 2018 but not 2020. In the absence of a licensed vaccine, further evaluation of the PNAG vaccine is warranted, including efforts to optimize the formulation and dose of this vaccine. IMPORTANCE Pneumonia caused by R. equi is an important cause of disease and death in foals worldwide for which a licensed vaccine is lacking. Foals are exposed to R. equi in their environment from birth, and they appear to be infected soon after parturition at an age when innate and adaptive immune responses are diminished. Results of this study indicate that higher activity of antibodies recognizing PNAG was associated with protection against R. equi pneumonia, indicating the need for further optimization of maternal vaccination against PNAG to protect foals against R. equi pneumonia.

N-acetyl-d-glucosamine-conjugated PAMAM dendrimers as dual receptor-targeting nanocarriers for anticancer drug delivery.

N-acetyl-d-glucosamine-labelled dendrimers (NAG-Dend) were synthesized for the targeted delivery of camptothecin (CPT) to A549 human lung adenocarcinoma cells, which overexpress glucose transporters and lectin receptors. CPT loaded, NAG-Dend (NAG-Dend-CPT) exhibited more rapid and higher cellular uptake than the unlabelled dendrimer formulation (Dend-CPT), leading to enhanced cytotoxicity. Compared with native CPT, NAG-Dend-CPT was 4.5 times more toxic to A549 cells. The anticancer activity of the different CPT formulations was dose and time dependent. NAG-Dend-CPT also increased reactive oxygen species generation, induced higher apoptosis and showed greater inhibition of A549 cell migration than Dend-CPT. The selective accumulation of NAG-Dend in the lungs of tumour-bearing mice confirmed that the NAG-based dendrimer system can target lung metastasis tumours in a biological system. Overall, our results show that NAG-conjugated dendrimers could be a promising nanocarrier system for the delivery of anticancer drugs, including CPT, to human lung cancer cells.

N-acetylglucosamine drives myelination by triggering oligodendrocyte precursor cell differentiation.

Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination promotes permanent neuro-axonal damage. Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling, and endocytosis. GlcNAc is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting platelet-derived growth factor receptor-α cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone)-induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage. Our data identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS.

N-Acetylglucosamine is the most effective glucosamine derivative for the treatment of membranous nephropathy in rats.

Nephroprotective drug development for optimizing treatment of chronic kidney disease (CKD) is an important task of pharmaceutical science. Our study evaluated nephroprotective properties of the two glucosamine derivatives N-acetylglucosamine and glucosamine hydrochloride in a 3-week-long parenteral and oral daily administration at doses of 50 mg/kg in rats with doxorubicin nephropathy. Nephroprotective activity (NA) was evaluated by determining the functional state of the kidneys, the level of azotemia and the activity of free-radical processes in the renal tissue. The results show a significant increase in renal excretory function, normalization of nitrogen metabolism and a decline of free-radical processes under the influence of both studied amino sugars in rats with doxorubicin nephropathy. I. m. route of administration yielded the highest efficacy for both amino sugars with the highest level of NA (83.3%) shown by N-acetylglucosamine. Thus N-acetylglucosamine in i. m. injections has the highest NA among the glucosamine derivatives, and is a promising agent for CKD treatment.

Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat Model of Postmenopausal Osteoporosis.

Postmenopausal osteoporosis has seriously affected the life quality of elderly women. A natural polymer, chitin, obtained from shells of crab and shrimp, has been widely used in the biomedical field owing to its nontoxicity, biocompatibility, and biodegradability. In this study, natural N-acetyl-d-glucosamine (NAG) was prepared from liquefied chitin. The protective activities of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and osteoblast-based models. Results showed that oral administration of NAG boosted trabecular bone volume and trabecular numbers. Additionally, the calcium content in the femur and tibia increased, and femoral biomechanical properties improved. Furthermore, NAG supplementation significantly lowered alkaline phosphatase levels and increased calcium content in the serum of ovariectomized rats. In vitro studies showed that NAG markedly promoted cell proliferation and stimulated osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG effectively protected osteoblasts from oxidative damage induced by hydrogen peroxide. In conclusion, our data provide an additional foundation for dietary supplementation of NAG, which could protect and reverse osteopenia in postmenopausal women.

2-(4-Methoxyphenyl)ethyl-2-Acetamido-2-deoxy-ß-d-pyranoside (A Salidroside Analog) Confers Neuroprotection with a Wide Therapeutic Window by Regulating Local Glucose Metabolism in a Rat Model of Cerebral Ischemic Injury.

2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-ß-d-pyranoside (salidroside analog-4g, SalA-4g), has shown neuroprotective prospects for the treatment of ischemic stroke. However, the dose-response and time window study for SalA-4g, and the mechanism of SalA-4g-mediated neuroprotection remain unclear. Here, we systematically investigated the therapeutic time window and dosage of SalA-4g in permanent focal cerebral ischemia in rats. SalA-4g dose-dependently improved stroke outcome. Either pre-treatment or post-treatment of SalA-4g exhibited notable neuroprotection, and maintained for up to 6 h after ischemia onset. Moreover, significant neurological functional recovery was found after SalA-4g administration in long-term functional assays. Further studies suggested that SalA-4g ameliorated neuronal cell death, elevated local glucose metabolism and enhanced the expression level of glucose transporter 1 and 3 in the ipsilateral cortex and striatum. We suggest that data of this study are critical in exploring the clinical application prospects of SalA-4g for the treatment of ischemic stroke.

Tuning carbohydrate density enhances protein binding and inhibition by glycosylated ß-sheet peptide nanofibers.

Carbohydrate-modified biomaterials are attractive candidates for disrupting natural protein-glycan binding events because they present ligands in multivalent arrangements that can address the weak affinity of monovalent protein-carbohydrate interactions. However, protein binding depends on physical aspects of immobilized carbohydrate display, such as density and valency, which are often difficult to predict and can vary for different types of biomaterials. Here, we report on protein interactions with ß-sheet peptide nanofibers with tunable immobilized carbohydrate content, which were prepared by co-assembling QQKFQFQFEQQ (Q11) with a glycosylated variant modified with N-acetylglucosamine (GQ11) at different molar ratios. The rate of protein binding increased as carbohydrate density decreased, with nanofibers having a GQ11 : Q11 molar ratio of 1 : 3 reaching equilibrium faster than formulations with a GQ11 mole fraction of 1. Larger proteins demonstrated a lower extent of binding than smaller proteins; however, the optimal range of carbohydrate densities was independent of the protein size. Nanofibers with the highest apparent protein binding affinity inhibited T cell death induced by wheat germ agglutinin (WGA) more effectively than did sub-optimal formulations, because they bound more protein within biologically relevant time frames (min to h). Collectively, these observations suggest that tuning carbohydrate density via co-assembly of glycosylated and non-glycosylated Q11 variants can maximize multivalent avidity effects while minimizing steric penalties. We anticipate that this approach will enable rapid iterative development of biomaterials with optimal activity for inhibiting the protein-glycan interactions implicated in disease progression.

Enhanced anticancer effect and reduced toxicity of doxorubicin in combination with thymoquinone released from poly-N-acetyl glucosamine nanomatrix in mice bearing solid Ehrlish carcinoma.

The incidence of breast cancer remarkably increases all over the world. Therefore, there is a great demand to introduce new approaches into cancer treatment field. The current study was designated to evaluate the role of doxorubicin (DOX) and/or thymoquinone (TQ) nanomatrix in potentiating the cytotoxicity of either drug, and to investigate the ability of TQ to reduce cardiotoxicity of DOX in solid Ehrlich carcinoma (SEC)-bearing mice. DOX and TQ were loaded into F2 gel, which is a fully-acetylated poly-N-acetyl glucosamine nanofiber. SEC was induced in female albino mice as a model for experimentally induced breast cancer. Mice were randomly divided into eight groups (n=10): normal control, tumor control, F2 gel, free DOX, DOX+F2 gel, free TQ, TQ+F2 gel, and DOX+TQ+F2 gel. On day 28th from tumor inoculation, mice were sacrificed and blood samples were collected for measurement of the cardiac markers; lactate dehydrogenase (LDH) and creatine kinase (CK-MB). In addition, cardiac tissue was utilized for determination of lipid peroxide, and tumor tissue was used for measurement of anti-apoptotic protein Bcl-2 as well as gene expression of the tumor suppressor gene P53. DOX and/or TQ showed a significant reduction in tumor volume, cardiac markers, tumor Bcl-2, and P53 upregulation compared to free conventional therapies. Co-treatment with DOX+TQ+F2 gel was superior to all other groups in exerting beneficial effects. Use of TQ as an adjuvant therapy with DOX could improve its cytotoxic effects and limit its cardiac toxicity. Furthermore, loading of DOX and/or TQ into F2 gel showed a remarkable anti-cancer activity.

Poly-N-Acetyl Glucosamine (sNAG) Enhances Early Rotator Cuff Tendon Healing in a Rat Model.

Rotator cuff injuries frequently require surgical repairs which have a high failure rate. Biological augmentation has been utilized in an attempt to improve tendon repair. Poly-N-acetyl glucosamine (sNAG) polymer containing nanofibers has been shown to increase the rate for healing of venous leg ulcers. The purpose of this study was to investigate the healing and analgesic properties of sNAG in a rat rotator cuff injury and repair model. 144 adult male Sprague-Dawley rats underwent a transection and repair of their left supraspinatus tendons. Half of the animals received a sNAG membrane on the tendon-to-bone insertion site. Animals were further subdivided, receiving 1 or 3 days of analgesics. Animals were sacrificed 2, 4, or 8 weeks post-injury. Animals sacrificed at 4 and 8 weeks underwent longitudinal in vivo ambulatory assessment. Histological properties were assessed at 2, 4, and 8 weeks, and mechanical properties at 4 and 8 weeks. In the presence of analgesics, tendons receiving the sNAG polymer had significantly increased max load and max stress at 4 weeks, but not at 8 weeks. Ambulatory improvements were observed at 14 days in stride length and speed. Therefore, sNAG improves tendon-to-bone healing in a rat rotator cuff detachment and repair model.

In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer Conjugate N-Acetyl Glucosamine (NAG)-PEG-Doxorubicin for Targeted Cancer Therapy.

A novel polymer-drug conjugate, polyethylene glycol-N-(acetyl)-glucosamine-doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer-drug conjugate comprised of polyethylene glycol-maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity studies and histopathological studies revealed that while maintaining its cytotoxicity towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs. Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for targeted cancer therapy.

PUGNAc treatment provokes globotetraosylceramide accumulation in human umbilical vein endothelial cells.

PUGNAc is a well-investigated inhibitor for protein-O-GlcNAcase, whereas recent investigations showed that PUGNAc had a broad range as inhibitor for cellular ß-hexosaminidases. Here we report that PUGNAc treatment provokes globotetraosylceramide (Gb4Cer) accumulation in human umbilical vein endothelial cells (HUVEC). HPLC analysis and a quantitative ELISA using newly developed anti-Gb4Cer monoclonal antibody revealed that PUGNAc treatment specifically increased the expression of Gb4Cer among glycosphingolipids expressed in HUVEC. Although the effect was weaker than PUGNAc, an O-GlcNAcase selective inhibitor (Thiamet-G) treatment also increased Gb4Cer levels in HUVEC. Furthermore, both of PUGNAc and Thiamet-G treatment up-regulated the expression levels of α-1,4-galactosyltransferase/Gb3Cer synthase gene which encodes a key enzyme in Gb4Cer synthesis. These results indicate that protein-O-GlcNAcylation can regulate the expression levels of cellular Gb4Cer.

Targeting the hexosamine biosynthetic pathway and O-linked N-acetylglucosamine cycling for therapeutic and imaging capabilities in diffuse large B-cell lymphoma.

The hexosamine biosynthetic pathway (HBP) requires two key nutrients glucose and glutamine for O-linked N-acetylglucosamine (O-GlcNAc) cycling, a post-translational protein modification that adds GlcNAc to nuclear and cytoplasmic proteins. Increased GlcNAc has been linked to regulatory factors involved in cancer cell growth and survival. However, the biological significance of GlcNAc in diffuse large B-cell lymphoma (DLBCL) is not well defined. This study is the first to show that both the substrate and the endpoint O-GlcNAc transferase (OGT) enzyme of the HBP were highly expressed in DLBCL cell lines and in patient tumors compared with normal B-lymphocytes. Notably, high OGT mRNA levels were associated with poor survival of DLBCL patients. Targeting OGT via small interference RNA in DLBCL cells inhibited activation of GlcNAc, nuclear factor kappa B (NF-κB), and nuclear factor of activated T-cells 1 (NFATc1), as well as cell growth. Depleting both glucose and glutamine in DLBCL cells or treating them with an HBP inhibitor (azaserine) diminished O-GlcNAc protein substrate, inhibited constitutive NF-κB and NFATc1 activation, and induced G0/G1 cell-cycle arrest and apoptosis. Replenishing glucose-and glutamine-deprived DLBCL cells with a synthetic glucose analog (ethylenedicysteine-N-acetylglucosamine [ECG]) reversed these phenotypes. Finally, we showed in both in vitro and in vivo murine models that DLBCL cells easily take up radiolabeled technetium-99m-ECG conjugate. These findings suggest that targeting the HBP has therapeutic relevance for DLBCL and underscores the imaging potential of the glucosamine analog ECG in DLBCL.

F2 Gel Matrix a Novel Delivery System for Immune and Gene Vaccinations.

Exploiting the immune system to abolish cancer growth via vaccination is a promising strategy but that is limited by many clinical issues. For DNA vaccines, viral vectors as a delivery system mediate a strong immune response due to their protein structure, which could afflect the cellular uptake of the genetic vector or even induce cytotoxic immune responses against transfected cells. Recently, synthetic DNA delivery systems have been developed and recommended as much easier and simple approaches for DNA delivery compared with viral vectors. These are based on the attraction of the positively charged cationic transfection reagents to negatively charged DNA molecules, which augments the cellular DNA uptake. In fact, there are three major cellular barriers which hinder successful DNA delivery systems: low uptake across the plasma membrane; inadequate release of DNA molecules with limited stability; and lack of nuclear targeting. Recently, a polysaccharide polymer produced by microalgae has been synthesized in a form of polymeric fiber material polyNacetyl glucosamine (pGlcNAc). Due its unique properties, the F2 gel matrix was suggested as an effective delivery system for immune and gene vaccinations.

Comparison of the chondroprotective effect of a novel hydrogel compound and traditional hyaluronate on rat cartilage in a papain-induced osteoarthritis model.

PURPOSE: The aim of this experimental study is to evaluate the efficacy of a novel intraarticular drug in a papain induced osteoarthritis (OA) rat model and compare with the traditional hyaluronat (HA) visco supplementation. METHODS: An early stage OA model was induced by the intra-articular injection of papain enzyme in the right knee joints of 44 Sprague-Dawley rats. Eleven rats (eleven right knees: papain group, 11 left knees: control group) were chosen randomly 28 days after the last injection and sacrificed for verifying OA. The remaining rats (n = 33) were randomly divided into 3 groups. Group 1 was injected 0,2 mL of sterile saline solution (0,9%), group 2 was injected 0,2 mL HA and the group 3 was injected 0,2 mL of HA-CSNAG (hyaluronat, chondritin sulfate, N-acetyl-d-glucosamine) combination in the right knees. Injections were performed on the 35th, the 42nd and the 49th days consecutively. Two weeks after the last injection, all groups were sacrificed to evaluate the severity of OA according to Mankin system. RESULTS: Early stage of OA was verified regarding total Mankin scores (p < 0.05). There was statistically significant difference between Group 1 and Group 2 (p < 0.05), between Group 1 and Group 3 (p < 0.05) on the 63th day regarding total Mankin scores. Group 3 showed statistically significant improvement in terms of proteoglycan content of matrix when compared to Group 2 (p < 0,05). CONCLUSION: HA-CS-NAG compound in hydrogel form is more chondroprotective to rats' cartilage when compared to HA during the early stages of OA.

Metabolic Reprogramming by Hexosamine Biosynthetic and Golgi N-Glycan Branching Pathways.

De novo uridine-diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis requires glucose, glutamine, acetyl-CoA and uridine, however GlcNAc salvaged from glycoconjugate turnover and dietary sources also makes a significant contribution to the intracellular pool. Herein we ask whether dietary GlcNAc regulates nutrient transport and intermediate metabolism in C57BL/6 mice by increasing UDP-GlcNAc and in turn Golgi N-glycan branching. GlcNAc added to the drinking water showed a dose-dependent increase in growth of young mice, while in mature adult mice fat and body-weight increased without affecting calorie-intake, activity, energy expenditure, or the microbiome. Oral GlcNAc increased hepatic UDP-GlcNAc and N-glycan branching on hepatic glycoproteins. Glucose homeostasis, hepatic glycogen, lipid metabolism and response to fasting were altered with GlcNAc treatment. In cultured cells GlcNAc enhanced uptake of glucose, glutamine and fatty-acids, and enhanced lipid synthesis, while inhibition of Golgi N-glycan branching blocked GlcNAc-dependent lipid accumulation. The N-acetylglucosaminyltransferase enzymes of the N-glycan branching pathway (Mgat1,2,4,5) display multistep ultrasensitivity to UDP-GlcNAc, as well as branching-dependent compensation. Indeed, oral GlcNAc rescued fat accumulation in lean Mgat5(-/-) mice and in cultured Mgat5(-/-) hepatocytes, consistent with N-glycan branching compensation. Our results suggest GlcNAc reprograms cellular metabolism by enhancing nutrient uptake and lipid storage through the UDP-GlcNAc supply to N-glycan branching pathway.

The exceptionally broad-based potential of active and passive vaccination targeting the conserved microbial surface polysaccharide PNAG.

A challenging component of vaccine development is the large serologic diversity of protective antigens. Remarkably, there is a conserved surface/capsular polysaccharide, one of the most effective vaccine targets, expressed by a large number of bacterial, fungal and eukaryotic pathogens: poly-N-acetyl glucosamine (PNAG). Natural antibodies to PNAG are poorly effective at mediating in vitro microbial killing or in vivo protection. Removing most of the acetate substituents to produce a deacetylated glycoform, or using synthetic oligosaccharides of poly-ß-1-6-linked glucosamine conjugated to carrier proteins, results in vaccines that elicit high levels of broad-based immunity. A fully human monoclonal antibody is highly active in laboratory and preclinical studies and has been successfully tested in a phase-I setting. Both the synthetic oligosaccharide conjugate vaccine and MAb will be further tested in humans starting in 2016; but, even if effective against only a fraction of the PNAG-producing pathogens, a major advance in vaccine-preventable diseases will occur.

A Firming Neck Cream Containing N-Acetyl Glucosamine Significantly Improves Signs of Aging on the Challenging Neck and Décolletage.

BACKGROUND: Noninvasive antiaging neck and décolletage treatments are highly sought after by aging patients. A topical cosmetic antiaging cream was formulated with skin matrix building and smoothing ingredients to help reverse visible signs of aging on the neck and décolletage, including laxity, crepiness, deep lines, and hyperpigmentation. OBJECTIVE: A clinical study was conducted to evaluate the efficacy and safety of the antiaging neck/décolletage cream over a 16-week treatment period. METHOD: Caucasian women with moderate texture (including wrinkles, fine lines, laxity, and/or crepiness) on the neck and hyperpigmentation on the décolletage used the test cream for 16 weeks. At weeks 0, 8, 12 and 16, the dermatologist investigator graded neck texture, décolletage texture and décolletage pigmentation using a 0-5 scale, and irritation/tolerability using a 0-4 scale. Subjects were photographed and provided self-assessment of their aging parameters as well as product tolerability. Chromameter measurements were collected in triplicate on the chest at weeks 0, 8, and 16 to quantitatively and objectively assess pigmentation. RESULTS: Forty-two women completed the study. All dermatologist-graded aging parameters were significantly improved at each time point, P<0.001. Chromameter measurements demonstrated significant improvements in brightness (L*) and redness (a*), P<0.05. Self-assessed aging parameters were significantly improved on the décolletage and neck, P<0.05. Digital photography demonstrated obvious antiaging effects including improved texture of neck and décolletage areas, reduced appearance of lines and wrinkles, reduced mottled hyperpigmentation, and a more youthful, firm appearance. The test cream was well-tolerated with no significant changes in irritation parameters throughout the study. CONCLUSION: The antiaging neck/décolletage cream delivered significant firming and smoothing effects with reduced appearance of hyperpigmentation and can be considered an effective topical homecare treatment option for patients seeking rejuvenation of this challenging area

Movardol® (N-acetylglucosamine, Boswellia serrata, ginger) supplementation in the management of knee osteoarthritis: preliminary results from a 6-month registry study.

OBJECTIVE: Knee Osteoarthritis (OA) is a chronic disease caused by the deterioration of cartilage in joints, which results in activation of the inflammatory response, pain, and impaired movement. Complementary therapies, particularly supplementation, in the management of moderate/severe knee OA have been gaining attention. This registry study aimed at evaluating the synergistic effect of Movardol®, a supplementation containing active ingredients with recognized anti-inflammatory activities on symptoms and levels of circulating biomarkers of knee OA. PATIENTS AND METHODS: 54 subjects with symptomatic, moderate knee OA freely decided to follow either a standard management (SM) (n = 26) or SM plus oral supplementation with Movardol® (n = 28). Movardol® supplementation containing N-acetyl-D-glucosamine, ginger, and Boswellia Serrata extract was taken at the following dosage: 3 tablets/day for one week and then 2 tablets/day. Several parameters were assessed at inclusion and after 1, 3 and 6 months: functional impairment by the Karnofsky Performance Scale Index; pain, stiffness, physical, social and emotional functions by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); total and pain-free walking distance; circulating biomarkers of inflammation and oxidative stress. RESULTS: Significant improvements in the functional outcomes and pain-free walking distance were observed after 1, 3 and 6 months in OA patients supplemented with Movardol®. Moreover, all the signs/symptoms of disease assessed by the WOMAC tended to regress over a 6-month period in patients following SM+supplementation. Inflammatory markers and plasmatic content of reactive oxygen species decreased over 6 months, in supplemented patients. Movardol® supplementation resulted to be safe and well tolerated, also showing the beneficial effect in term of a decrease in pharmacological and non-pharmacological treatments and, consequently, reduction in management costs. CONCLUSIONS: These preliminary results indicate the efficacy and safety of Movardol® supplementation in the management of moderate knee OA.