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Neuroprotective Effects of Cranberry Juice Treatment in a Rat Model of Parkinson's Disease

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Authors
Witucki Ł, Kurpik M, Jakubowski H, Szulc M, Łukasz Mikołajczak P, Jodynis-Liebert J, Kujawska M
Journal
Nutrients. 2022 May 11;14(10):2014. doi: 10.3390/nu14102014. PMID: 35631155; PMCID: PMC9144186
Abstract

Rich in polyphenols, cranberry juice (CJ) with high antioxidant activity is believed to contribute to various health benefits. However, our knowledge of the neuroprotective potential of cranberries is limited. Previously, we have demonstrated that CJ treatment controls oxidative stress in several organs, with the most evident effect in the brain. In this study, we examined the capability of CJ for protection against Parkinson’s disease (PD) in a rotenone (ROT) rat model. Wistar rats were administered with CJ in a dose of 500 mg/kg b.w./day (i.g.) and subcutaneously injected with ROT (1.3 mg/kg b.w./day). The experiment lasted 45 days, including 10 days pre-treatment with CJ and 35 days combined treatment with CJ and ROT. We quantified the expression of α-synuclein and apoptosis markers in the midbrain, performed microscopic examination, and assessed postural instability to evaluate the CJ neuroprotective effect. Our results indicate that the juice treatment provided neuroprotection, as evidenced by declined α-synuclein accumulation, Bax and cleaved/active caspase-9 expression, and normalized cytochrome c level that was accompanied by the enhancement of neuronal activity survival and improved postural instability. Importantly, we also found that long-term administration of CJ alone in a relatively high dose may exert a deleterious effect on cell survival in the midbrain. 

Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome

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Authors
Weh KM, Howard CL, Zhang Y, Tripp BA, Clarke JL, Howell AB, Rubenstein JH, Abrams JA, Westerhoff M, Kresty LA
Journal
JCI Insight. 2024 Feb 8;9(6):e168112. doi: 10.1172/jci.insight.168112. PMID: 38329812; PMCID: PMC11063939
Abstract

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett’s esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome–esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 μg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinisEscherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4Cd14CrpCxcl1Il6Il1bLbpLcn2Myd88Nfkb1Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

Recurrent UTI in Women-Risk Factors and Management

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Authors
Lazarus JE, Gupta K
Journal
Infect Dis Clin North Am. 2024 Jun;38(2):325-341. doi: 10.1016/j.idc.2024.03.010. Epub 2024 Apr 10. PMID: 38599896
Abstract

Urinary tract infections (UTIs) are common in women; more than 50% of women will be diagnosed with a UTI in her lifetime. Many of these women will go on to develop recurrent UTI. Nevertheless, evidence-based prevention of recurrent UTI is under-utilized. Here, the authors provide detailed practical advice on UTI prevention with a thorough review of the evidence. Non-antibiotic prevention measures discussed include increased fluid intake, vaginal estrogen therapy, methenamine, and cranberry. Antibiotic prophyalxis for carefully selected patients is also discussed.

The Development and Evaluation of a Literature-Based Dietary Index for Gut Microbiota

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Authors
Kase BE, Liese AD, Zhang J, Murphy EA, Zhao L, Steck SE
Journal
Nutrients. 2024 Apr 3;16(7):1045. doi: 10.3390/nu16071045. PMID: 38613077; PMCID: PMC11013161
Abstract

The aim of the study was to develop and evaluate a novel dietary index for gut microbiota (DI-GM) that captures dietary composition related to gut microbiota profiles. We conducted a literature review of longitudinal studies on the association of diet with gut microbiota in adult populations and extracted those dietary components with evidence of beneficial or unfavorable effects. Dietary recall data from the National Health and Nutrition Examination Survey (NHANES, 2005–2010, n = 3812) were used to compute the DI-GM, and associations with biomarkers of gut microbiota diversity (urinary enterodiol and enterolactone) were examined using linear regression. From a review of 106 articles, 14 foods or nutrients were identified as components of the DI-GM, including fermented dairy, chickpeas, soybean, whole grains, fiber, cranberries, avocados, broccoli, coffee, and green tea as beneficial components, and red meat, processed meat, refined grains, and high-fat diet (≥40% of energy from fat) as unfavorable components. Each component was scored 0 or 1 based on sex-specific median intakes, and scores were summed to develop the overall DI-GM score. In the NHANES, DI-GM scores ranged from 0–13 with a mean of 4.8 (SE = 0.04). Positive associations between DI-GM and urinary enterodiol and enterolactone were observed. The association of the novel DI-GM with markers of gut microbiota diversity demonstrates the potential utility of this index for gut health-related studies.

The Diagnosis, Treatment, and Prevention of Recurrent Urinary Tract Infection

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Authors
Schmiemann G, Kranz J, Mandraka F, Schubert S, Wagenlehner F, Gágyor I
Journal
Dtsch Arztebl Int. 2024 May 31;(Forthcoming):arztebl.m2024.0068. doi: 10.3238/arztebl.m2024.0068. Epub ahead of print. PMID: 38686602
Abstract

Background: Urinary tract infection has a one-year prevalence of 11% in women and ranges among the most common reasons for consulting a primary care physician and for receiving a prescription for antibiotics. In the case of recurrent urinary tract infection (rUTI), there are questions about the further work-up, treatment, and preventive measures.

Methods: The systematic literature search performed for the update of the German clinical practice guideline on uncomplicated urinary tract infection (043-044) (up to February 2022) was supplemented with a selective search for clinical trials (up to August 2023).

Results: Urine culture and ultrasonography are reasonable steps in the diagnostic evaluation of rUTI. Further invasive testing is suggested for men but is not routinely indicated for women. Antibiotics are among the most effective preventive measures (risk ratio [RR] 0.15, 95% confidence interval [0.1; 0.3]) but carry a high risk of side effects. Non-antibiotic preparations such as cranberry juice (RR 0.74 [0.5; 0.99]), mannose (RR 0.23 [0.14; 0.37]), and vaginal estrogen (RR, 0.42 [0.30; 0.59]) can also reduce the infection rate, with a low risk of side effects. Increased daily fluid intake has been shown to lower infection rates in the short term (odds ratio [OR] 0.13 [0.07; 0.25]); the use of hygienically advisable wiping techniques after passing stool or urine has been little studied but can be implemented with no risk.

Conclusion: rUTI poses a challenge for the treating physician. The measures to be taken must be considered on an individual basis. Vulnerable groups, such as older patients, need special attention.

The role of intestinal microbiota and microRNAs in the anti-inflammatory effects of cranberry: from pre-clinical to clinical studies

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Authors
Taibi A, Lofft Z, Laytouni-Imbriaco B, Comelli EM
Journal
Front Nutr. 2023 May 23;10:1092342. doi: 10.3389/fnut.2023.1092342. PMID: 37287997; PMCID: PMC10242055
Abstract

Cranberries have known anti-inflammatory properties, which extend their benefits in the context of several chronic diseases. These benefits highly rely on the polyphenol profile of cranberries, one of few foods rich in A-type proanthocyanidin (PAC). A-type PAC comprises flavan-3-ol subunits with an additional interflavan ether bond in the conformational structure of the molecule, separating them from the more commonly found B-type PAC. PACs with a degree of polymerization higher than three are known to reach the colon intact, where they can be catabolyzed by the gut microbiota and biotransformed into lower molecular weight organic acids that are available for host absorption. Gut microbiota-derived metabolites have garnered much attention in the past decade as mediators of the health effects of parent compounds. Though, the mechanisms underlying this phenomenon remain underexplored. In this review, we highlight emerging evidence that postulates that polyphenols, including ones derived from cranberries, and their metabolites could exert anti-inflammatory effects by modulating host microRNAs. Our review first describes the chemical structure of cranberry PACs and a pathway for how they are biotransformed by the gut microbiota. We then provide a brief overview of the benefits of microbial metabolites of cranberry in the intestinal tract, at homeostasis and in inflammatory conditions. Finally, we discuss the role of microRNAs in intestinal health and in response to cranberry PAC and how they could be used as targets for the maintenance of intestinal homeostasis. Most of this research is pre-clinical and we recognize that conducting clinical trials in this context has been hampered by the lack of reliable biomarkers. Our review discusses the use of miRNA as biomarkers in this context.

Uropathogenic Escherichia coli endeavors: an insight into the characteristic features, resistance mechanism, and treatment choice

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Authors
Arafi V, Hasani A, Sadeghi J, Varshochi M, Poortahmasebi V, Hasani A, Hasani R
Journal
Arch Microbiol. 2023 May 8;205(6):226. doi: 10.1007/s00203-023-03553-5. PMID: 37156886
Abstract

Uropathogenic Escherichia coli (UPEC) are the strains diverted from the intestinal status and account mainly for uropathogenicity. This pathotype has gained specifications in structure and virulence to turn into a competent uropathogenic organism. Biofilm formation and antibiotic resistance play an important role in the organism’s persistence in the urinary tract. Increased consumption of carbapenem prescribed for multidrug-resistant (MDR) and Extended-spectrum-beta lactamase (ESBL)-producing UPECs, has added to the expansion of resistance. The World Health Organization (WHO) and Centre for Disease Control (CDC) placed the Carbapenem-resistant Enterobacteriaceae (CRE) on their treatment priority lists. Understanding both patterns of pathogenicity, and multiple drug resistance may provide guidance for the rational use of anti-bacterial agents in the clinic. Developing an effective vaccine, adherence-inhibiting compounds, cranberry juice, and probiotics are non-antibiotical approaches proposed for the treatment of drug-resistant UTIs. We aimed to review the distinguishing characteristics, current therapeutic options and promising non-antibiotical approaches against ESBL-producing and CRE UPECs.

Ursolic Acid against Prostate and Urogenital Cancers: A Review of In Vitro and In Vivo Studies

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Authors
Kornel A, Nadile M, Retsidou MI, Sakellakis M, Gioti K, Beloukas A, Sze NSK, Klentrou P, Tsiani E
Journal
Int J Mol Sci. 2023 Apr 18;24(8):7414. doi: 10.3390/ijms24087414. PMID: 37108576; PMCID: PMC10138876
Abstract

Prostate cancer is the second most diagnosed form of cancer in men worldwide and accounted for roughly 1.3 million cases and 359,000 deaths globally in 2018, despite all the available treatment strategies including surgery, radiotherapy, and chemotherapy. Finding novel approaches to prevent and treat prostate and other urogenital cancers effectively is of major importance. Chemicals derived from plants, such as docetaxel and paclitaxel, have been used in cancer treatment, and in recent years, research interest has focused on finding other plant-derived chemicals that can be used in the fight against cancer. Ursolic acid, found in high concentrations in cranberries, is a pentacyclic triterpenoid compound demonstrated to have anti-inflammatory, antioxidant, and anticancer properties. In the present review, we summarize the research studies examining the effects of ursolic acid and its derivatives against prostate and other urogenital cancers. Collectively, the existing data indicate that ursolic acid inhibits human prostate, renal, bladder, and testicular cancer cell proliferation and induces apoptosis. A limited number of studies have shown significant reduction in tumor volume in animals xenografted with human prostate cancer cells and treated with ursolic acid. More animal studies and human clinical studies are required to examine the potential of ursolic acid to inhibit prostate and other urogenital cancers in vivo. 

A Cranberry Concentrate Decreases Adhesion and Invasion of Escherichia coli (AIEC) LF82 In Vitro.

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Authors
Zhang D, Verstrepen L, De Medts J, Duysburgh C, Van den Abbeele P, Marzorati M, Khoo C
Journal
Pathogens. 10(9), 2021 Sep 18
Abstract

While many beneficial host-microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn's disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type M (CTM) on adherent-invasive Escherichia coli (AIEC) LF82, a pathobiont associated with CD. Different stages of pathogenic infection were investigated: (i) colonization of the mucus layer, and (ii) adhesion to and (iii) invasion of the epithelial cells. Following 48 h of fecal batch incubation, 0.5 and 1 mM of CTM significantly altered AIEC LF82 levels in a simulated mucus layer, resulting in a decrease of 50.5% in the untreated blank, down to 43.0% and 11.4%, respectively. At 1 mM of CTM, the significant decrease in the levels of AIEC LF82 coincided with a stimulation of the metabolic activity of the background microbiota. The increased levels of health-associated acetate (+7.9 mM) and propionate levels (+3.5 mM) suggested selective utilization of CTM by host microorganisms. Furthermore, 1 mM of both fermented and unfermented CTM decreased the adhesion and invasion of human-derived epithelial Caco-2 cells by AIEC LF82. Altogether, this exploratory in vitro study demonstrates the prebiotic potential of CTM and supports its antipathogenic effects through direct and/or indirect modulation of the gut microbiome.

A prospective randomized study to define the role of low dose continuous prophylactic antibiotics and anti-adherence agents in altering the microbial colonization related to indwelling double-J stents.

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Authors
Madhavan K, Rustagi S, Jena R, Singh UP, Ansari MS, Srivastava A, Kapoor R, Sureka SK
Journal
Asian Journal of Urology. 8(3):269-274,
Abstract

OBJECTIVE: Despite conflicting evidence, it is common practice to use continuous antibiotic prophylaxis (CAP) in patients with indwelling double-J (DJ) stents. Cranberry extracts and d-mannose have been shown to prevent colonization of the urinary tract. We evaluated their role in this setting.METHODS: We conducted a prospective randomized study to evaluate patients with indwelling DJ stents following urological procedures. They were randomized into three groups. Group A (n=46) received CAP (nitrofurantoin 100 mg once daily [OD]). Group B (n=48) received cranberry extract 300 mg and d-mannose 600 mg twice daily (BD). Group C (n=40) received no prophylaxis. The stents were removed between 15 days and 45 days after surgery. Three groups were compared in terms of colonization of stent and urine, stent related symptoms and febrile urinary tract infections (UTIs) during the period of indwelling stent and until 1 week after removal.RESULTS: In Group A, 9 (19.5%) patients had significant bacterial growth on the stents. This was 8 (16.7%) in the Group B and 5 (12.5%) in Group C (p-value: 0.743). However, the culture positivity rate of urine specimens showed a significant difference (p-value: 0.023) with Group B showing least colonization of urine compared to groups A and C. There was no statistically significant difference in the frequency of stent related symptoms (p-value: 0.242) or febrile UTIs (p-value: 0.399) among the groups.CONCLUSION: Prophylactic agents have no role in altering bacterial growth on temporary indwelling DJ stent, stent related symptoms or febrile UTIs. Cranberry extract may reduce the colonization of urinary tract, but its clinical significance needs further evaluation.