Background: D-mannose, an epimer of glucose, which is abundant in some fruits, such as cranberry, has been previously reported to inhibit urinary tract infection. In recent years, the potential function of D-mannose has been broadened into the regulation of other inflammation diseases and cancer. It was reported that D-mannose can increase reactive oxygen species (ROS) production, while IDH2 is important for the generation of NADPH, the crucial reducing factor. These findings prompted us to determine whether D-mannose can regulate IDH2 and IDH2-mediated NADPH production in tumor.

Methods: The breast cancer cell line MDA-MB-231 was cultured and treated with 100mM D-mannose. IDH2 expression was detected by Western Blot and qRT-PCR. RNA-seq was conducted to identify the differentially expressed genes. BioGRID database was used to find the IDH2 interactors. Tumor cells were collected to measure the NADPH production using the NADP+/NADPH detection Kit. Colony formation assay and CCK-8 assay were conducted to evaluate the proliferation of cells.

Results: D-mannose can promote IDH2 protein degradation through ubiquitination-proteasome pathway. Mechanistically, D-mannose treatment upregulated the expression of an E3 ligase - RNF185, which can interact with IDH2 and promotes its proteasomal degradation. Consequently, IDH2-mediated NADPH production was inhibited by D-mannose, the proliferation of breast cancer cells was retarded, and the sensitivity to pro-oxidant of breast cancer cells was elevated.

Conclusions: Our study demonstrated that D-mannose can degrade IDH2 and inhibit the production of NADPH to suppress the proliferation of breast cancer cells and render the breast cancer cells more sensitive to pro-oxidant treatment. Furthermore, we illustrated the E3 ligase RNF185 plays an important role in D-mannose-mediated proteasomal degradation of IDH2. 

Cranberry-derived proanthocyanidin (PAC) is processed by the gut microbiota to produce 3-(4-hydroxyphenyl)-propionic acid (HPPA), among other metabolites. These data are in support of the article entitled, Cranberry proanthocyanidin and its microbial metabolite 3,4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells, published in Molecular Nutrition and Food Research [1]. Here we describe data generated by nCounter((R) ) Human v3 miRNA Expression Panel of RNA obtained from Caco-2BBe1 cells exposed to two different concentrations of cranberry extract rich in PAC (50 mu g/ml or 100 mu g/ml) or 3-(4-hydroxyphenyl)-propionic acid (5 mu g/ml or 10 mu g/ml) for 24 h, then stimulated with 1 ng/ml of IL-1 beta or not (mock) for three hours. The raw data are publicly available at the NCBI GEO database GSE237078. This work also includes descriptive methodological procedures, treatment-responsive microRNA (miRNA) expression profiles in Caco-2BBe1 cells, and in silico mRNA gene target and pathway enrichment analyses of significantly differentially expressed miRNAs (q < 0.001). Cranberry and its components have recognized health benefits, particularly in relation to combatting inflammation and pathogenic bacterial adhesion. These data will be valuable as a reference to study the response of intestinal cells to other polyphenol-rich food sources, analyze gut microbial responses to cranberry and its metabolites in different cell lines and mammalian hosts to elucidate individualized effects, and to delineate the role of the gut microbiota in facilitating the benefits of cranberry. Moreover, these data will aid in expanding our knowledge on the mechanisms underlying the benefits of cranberry and its components. (c) 2024 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Microbial biofilms are resilient, immune-evasive, often antibiotic-resistant health challenges, and increasingly the target for research into novel therapeutic strategies. We evaluated the effects of a nutraceutical enzyme and botanical blend (NEBB) on established biofilm. Five microbial strains with known implications in chronic human illnesses were tested: Candida albicans, Staphylococcus aureus, Staphylococcus simulans (coagulase-negative, penicillin-resistant), Borrelia burgdorferi, and Pseudomonas aeruginosa. The strains were allowed to form biofilm in vitro. Biofilm cultures were treated with NEBB containing enzymes targeted at lipids, proteins, and sugars, also containing the mucolytic compound N-acetyl cysteine, along with antimicrobial extracts from cranberry, berberine, rosemary, and peppermint. The post-treatment biofilm mass was evaluated by crystal-violet staining, and metabolic activity was measured using the MTT assay. Average biofilm mass and metabolic activity for NEBB-treated biofilms were compared to the average of untreated control cultures. Treatment of established biofilm with NEBB resulted in biofilm-disruption, involving significant reductions in biofilm mass and metabolic activity for Candida and both Staphylococcus species. For B. burgdorferi, we observed reduced biofilm mass, but the remaining residual biofilm showed a mild increase in metabolic activity, suggesting a shift from metabolically quiescent, treatment-resistant persister forms of B. burgdorferi to a more active form, potentially more recognizable by the host immune system. For P. aeruginosa, low doses of NEBB significantly reduced biofilm mass and metabolic activity while higher doses of NEBB increased biofilm mass and metabolic activity. The results suggest that targeted nutraceutical support may help disrupt biofilm communities, offering new facets for integrative combinational treatment strategies.

Background: The aim of this double-blind randomized placebo-controlled clinical trial was to evaluate the efficacy of a multinutrient supplement as an add-on therapy to scaling and root planing for patients with periodontitis. 

Methods: Forty-two patients with stage III or IV periodontitis were randomly allocated to a 2-month treatment of either a multinutrient supplement containing vitamin C, vitamin E, zinc, selenium, alpha-lipoic-acid, cranberry extract, grapeseed extract, and coenzyme Q10 or placebo capsules as an adjunct to conservative periodontal therapy. Periodontal parameters, including probing pocket depth, gingival recession, bleeding on probing, approximal plaque index, and papillary bleeding index, were assessed. Clinical attachment loss, periodontal inflamed surface area, periodontal epithelial surface area, and percentages of pocket sites with & LE;3, & LE;4, & GE;5, & GE;6, & GE;7, and & GE;4 mm with bleeding on probing were calculated. 

Results: All clinical parameters significantly improved from baseline to reevaluation within each group (p < 0.05). Multinutrient intake resulted in a significantly higher reduction of probing-pocket-depth (-0.75 & PLUSMN; 0.42 mm) and bleeding-on-probing (-21.9 & PLUSMN; 16.1%) from baseline to reevaluation compared with placebo (-0.51 & PLUSMN; 0.30 mm, p = 0.040 and -12.5 & PLUSMN; 9.8%, p = 0.046, respectively). All periodontal parameters showed insignificantly higher improvements in patients receiving the supplement compared with those receiving the placebo (p > 0.05). 

Conclusions: Multinutrient supplementation as an adjunct to nonsurgical treatment of periodontitis showed some additional benefit regarding probing-pocket-depth and bleeding-on-probing. However, the clinical relevance needs to be further explored.

OBJECTIVE: To provide an overview of the available scientific evidence from in vitrostudies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans).

METHODS: This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias.

RESULTS: Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5mg/mL to 25mg/mL, and GSE exerts a similar effect from 0.5mg/mL to 250mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content.

CONCLUSIONS: The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.

Objectives: Polyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating Helicobacter pylori.

Design: Systematic review and meta-analysis.

Methods: Literature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis. The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species.

Results:12 trials were included in the meta-analysis. The total eradication rate of H.pylori in the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95% CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18). In subgroup analyses, the H.pylori eradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03).

Conclusion: Polyphenol compounds can improve H.pylori eradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found.PROSPERO registration numberCRD42022307477.

Background: Pre- and probiotics may help restore a dysbiotic oral ecosystem. The first years of life provide a window of opportunity to modulate the composition of the oral microbiota and prevent disease.

Objectives: The aim of the present study was to investigate the effect of a tablet containing inactivated Ligilactobacillus salivarius CECT 5317 and the cranberry extract on the development of caries in active preschool children.

Material and methods: The study employed a randomized, placebo-controlled, double-blind design. Preschool children (N = 73) with at least one active carious lesion were enrolled and randomly assigned to the test group or the placebo group. The intervention period was 3 months. Caries was assessed according to the International Caries Detection and Assessment System (ICDAS) II criteria at baseline and after 9 months, and oral hygiene was evaluated with the simplified oral hygiene index (OHI-S). The salivary counts of Streptococcus mutans and Lactobacillus spp. were determined at baseline, and then after 3 and 9 months through the conventional cultivation on TYCSB and MRS agar, respectively.

Results: Sixty children completed the trial (a dropout rate of 19%). The baseline caries prevalence was high in both groups (similar to 71%) and there were no major differences between the groups with regard to background variables. The 9-month incidence of initial carious lesions (ICDAS 1+2) was significantly lower in the test group as compared to the placebo group (p < 0.05). The plaque levels, and the salivary counts of S. mutans and Lactobacillus spp. remained unchanged in both groups throughout the study.

Conclusions: A daily intake of a tablet containing a paraprobiotic and the cranberry extract reduced the 9-month incidence of initial non-cavitated carious lesions in caries-active preschool children. The present study is one of the first to show the impact of synbiotics on the development of caries in children.

Background: Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD). 

Objectives: To evaluate cranberry (Vaccinium macrocarpon) supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. 

Design/Participants: A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. 

Measurements: The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method. 

Results: Twenty-five patients completed the study: 12 in the cranberry group (56.7 +/- 7.5 years and body mass index (BMI) of 29.6 +/- 5.5 kg/m(2)) and 13 in the placebo group (58.8 +/- 5.1 years and BMI 29.8 +/- 5.4 kg/m(2)). There were no differences in NF-kB or Nrf2 mRNA expressions ( p = 0.99 and p = 0.89 ) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation. 

Conclusions: The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919.

Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques.

Purpose of review: There is a growing interest in nonantibiotic prevention strategies for recurrent urinary tract infections (rUTIs). Our objective is to provide a focused, pragmatic review of the latest evidence.

Recent findings: Vaginal estrogen is well tolerated and effective for preventing rUTI in postmenopausal women. Cranberry supplements at sufficient doses are effective in preventing uncomplicated rUTI. Methenamine, d-mannose, and increased hydration all have evidence to support their use, although the evidence is of somewhat variable quality.There is sufficient evidence to recommend vaginal estrogen and cranberry as first-line rUTI prevention strategies, particularly in postmenopausal women. Prevention strategies can be used in series or in tandem, based on patient preference and tolerance for side effects, to create effective nonantibiotic rUTI prevention strategies.