Search Results (10)

Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing diarrhea in humans and animals, with increasing antimicrobial resistance posing a growing challenge in recent years. Lytic bacteriophages (phages) offer a targeted and environmentally sustainable approach to combating bacterial infections, particularly in eliminating drug-resistant strains. In this study, ETEC strains were utilized as indicators, and a stable, high-efficiency phage, designated vB_EcoM_JE01 (JE01), was isolated from pig farm manure. The genome of JE01 was a dsDNA molecule, measuring 168.9 kb, and a transmission electron microscope revealed its characteristic T4-like Myoviridae morphology. JE01 effectively lysed multi-drug-resistant ETEC isolates. Stability assays demonstrated that JE01 retained its activity across a temperature range of 20 °C to 50 °C and a pH range of 3–11, showing resilience to ultraviolet radiation and chloroform exposure. Furthermore, JE01 effectively suppressed ETEC adhesion to porcine intestinal epithelial cells (IPEC-J2), mitigating the inflammatory response triggered by ETEC. To investigate the in vivo antibacterial efficacy of phage JE01 preparations, a diarrhea model was established using germ-free mice infected with a drug-resistant ETEC strain. The findings indicated that 12 h post-ETEC inoculation, intragastric administration of phage JE01 significantly reduced mortality, alleviated gastrointestinal lesions, decreased ETEC colonization in the jejunum, and suppressed the expression of the cytokines IL-6 and IL-8. These results demonstrate a therapeutic benefit of JE01 in treating ETEC-induced diarrhea in mice. Additionally, a fluorescent phage incorporating red fluorescent protein (RFP) was engineered, and the pharmacokinetics of phage therapy were preliminarily assessed through intestinal fluorescence imaging in mice. The results showed that the phage localized to ETEC in the jejunum rapidly, within 45 min. Moreover, the pharmacokinetics of the phage were markedly slowed in the presence of its bacterial target in the gut, suggesting sustained bacteriolytic activity in the ETEC-infected intestine. In conclusion, this study establishes a foundation for the development of phage-based therapies against ETEC. Full article

Background: RICAP is a recognized adverse effect of radiation therapy (RT) that can adversely affect cancer patients’ quality of life. Data on the clinical characteristics and outcomes of RICAP are scarce. We aimed to analyze the clinical and endoscopic characteristics of acute or chronic radiation-induced colitis and proctopathy (ARICAP and CRICAP) based on symptom onset after RT (≤ or >45 days, respectively). Methods: This is a retrospective observational study of a single tertiary cancer center, from January 2010 and December 2018, of cancer patients with endoscopically confirmed ARICAP and CRICAP. We conducted univariate and multivariate logistic regression analyses to associate clinical variables with endoscopic and medical outcomes. Results: One hundred and twelve patients were included (84% Caucasian; 55% female; median age of 59 years); 46% had ARICAP with non-bloody diarrhea as the predominant symptom, whereas 55% had CRICAP with mostly bloody diarrhea. Neovascularization was the most frequent finding on endoscopy, followed by bleeding. ARICAP patients more often received medical management (p < 0.001), whereas CRICAP patients with bleeding more often received argon plasma coagulation (APC) (p = 0.002). Female sex and undergoing less-intense RT treatments were more associated with medical treatment; bleeding clinically and during the endoscopy was more associated with APC treatment. However, APC treatment did not significantly reduce bleeding recurrence or RICAP symptoms. Conclusion: Patients with ARICAP and CRICAP experience different symptoms. Medical management should be considered before endoscopic therapy. APC may be useful in patients with endoscopically apparent bleeding. Full article

Thyroid carcinoma is the most common cancer of the endocrine system, accounting for 12% of all cancer cases in adolescents in the United States. Radioiodine therapy plays a key role in differentiated thyroid cancer (DTC) treatment. This double-blind, randomized, placebo-controlled clinical trial was aimed at evaluating the effect of probiotics supplementation in reducing the acute side-effects of radioiodine therapy in PTC patients. Fifty-six patients were randomly divided into four groups: one placebo and three intervention groups. The probiotics product used in this study was LactoCare (ZistTakhmir Co., Tehran, Iran), a multi-strain commercially available symbiotic containing 12 strains of probiotic species including Lactobacillus strains, Bifidobacteria strains, and Streptococcus thermophilus, plus Fructo-oligosaccharides as the prebiotic. Group 0 was our placebo group (no probiotics), while the other three groups received probiotics capsules for 2/4 days, starting only 2 days prior to radioiodine therapy, only 4 days after radioiodine therapy or 2 days prior and 4 days after radioiodine therapy. Six patients were withdrawn during the study because of poor compliance or at their own request. The symptoms reported by patients including data about the incidence and duration of each complication were recorded. The probiotics’ effectiveness was confirmed for dry mouth and taste loss or change when it was administered prior to the radioiodine treatment. The benefit was not confirmed for other radiation-induced complications such as pain and swelling in the neck, nausea and vomiting, salivary gland swelling, and diarrhea. Further large-scale clinical trials are warranted to improve our knowledge in this quickly evolving field. Full article

The Licania genus has been used in the treatment of dysentery, diabetes, inflammation, and diarrhea in South America. Of these plants, the strong anti-inflammatory activity of Licania macrocarpa Cuatrec (Chrysobalanaceae) has been reported previously. However, the beneficial activities of this plant on skin health have remained unclear. This study explores the protective activity of a methanol extract (50–100 μg/mL) in the aerial parts of L. macrocarpa Cuatrec (Lm-ME) and its mechanism, in terms of its moisturizing/hydration factors, skin wrinkles, UV radiation-induced cell damage, and radical generation (using RT/real-time PCR, carbazole assays, flowcytometry, DPPH/ABTS, and immunoblotting analysis). The anti-pigmentation role of Lm-ME was also tested by measuring levels of melanin, melanogenesis-related genes, and pigmentation-regulatory proteins. Lm-ME decreased UVB-irradiated death in HaCaT cells by suppressing apoptosis and inhibited matrix metalloproteinases 1/2 (MMP1/2) expression by enhancing the activity of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. It was confirmed that Lm-ME displayed strong antioxidative activity. Lm-ME upregulated the expression of hyaluronan synthases-2/3 (HAS-2/3) and transglutaminase-1 (TGM-1), as well as secreted levels of hyaluronic acid (HA) via p38 and JNK activation. This extract also significantly inhibited the production of hyaluronidase (Hyal)-1, -2, and -4. Lm-ME reduced the melanin expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1/2 (TYRP-1/2) in α-melanocyte-stimulating hormone (α-MSH)-treated B16F10 cells via the reduction of cAMP response element-binding protein (CREB) and p38 activation. These results suggest that Lm-ME plays a role in skin protection through antioxidative, moisturizing, cytoprotective, and skin-lightening properties, and may become a new and promising cosmetic product beneficial for the skin. Full article

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females (incidence 16.4/10,000) and the third in males (incidence 23.4/10,000) worldwide. Surgery, chemotherapy (CTx), radiation therapy (RTx), or a combined treatment of those are the current treatment modalities for primary CRC. Chemotherapeutic drug-induced gastrointestinal (GIT) toxicity mainly presents as mucositis and diarrhea. Preclinical studies revealed that probiotic supplementation helps prevent CTx-induced side effects by reducing oxidative stress and proinflammatory cytokine production and promoting crypt cell proliferation. Moreover, probiotics showed significant results in preventing the loss of body weight (BW) and reducing diarrhea. However, further clinical studies are needed to elucidate the exact doses and most promising combination of strains to reduce or prevent chemotherapy-induced side effects. The aim of this review is to overview currently available literature on the impact of probiotics on CTx-induced side effects in animal studies concerning CRC treatment and discuss the potential mechanisms based on experimental studies’ outcomes. Full article

The protective effects of probiotic supplementation against radiation-induced diarrhea (RID) have been reported in previous systematic reviews; however so far, only non-conclusive results have been obtained. The objective of this study was to systematically update and evaluate the available evidence for probiotic supplementation. The protocol of this systematic review has been registered (CRD42018106059) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary efficacy outcome was the incidence of RID. Secondary outcomes were the incidence of watery stool, soft stool, and antidiarrheal medication use. There were eight trials, and a total of 1116 participants were included in the primary analysis. Compared with placebo, probiotics were associated with a lower risk of RID [risk ratio (RR) = 0.62, 95% CI = 0.46, 0.83]. A requisite heterogeneity-adjusted trial sequential analysis indicated conclusive evidence for this beneficial effect. No statistically significant reduction in RID (RR = 0.52, 95% CI = 0.14, 1.91) was observed on subgroup analysis in patients receiving both radiation therapy and chemotherapy. However, those patients receiving only radiation therapy (RT) demonstrated significant benefit (RR = 0.61, 95% CI = 0.48, 0.78). There was a significant difference in the antidiarrheal medication use (RR = 0.54, 95% CI = 0.35, 0.84) observed with the use of probiotics. However, no significant difference was observed for the incidence of soft and watery stool. The use of probiotics is beneficial in preventing RID in patients receiving RT. Full article

Pelvic radiotherapy has been frequently reported to cause acute and late onset gastrointestinal (GI) toxicities associated with significant morbidity and mortality. Although the underlying mechanisms of pelvic radiation-induced GI toxicity are poorly understood, they are known to involve a complex interplay between all cell types comprising the intestinal wall. Furthermore, increasing evidence states that the human gut microbiome plays a role in the development of radiation-induced health damaging effects. Gut microbial dysbiosis leads to diarrhea and fatigue in half of the patients. As a result, reinforcement of the microbiome has become a hot topic in various medical disciplines. To counteract GI radiotoxicities, apart from traditional pharmacological compounds, adjuvant therapies are being developed including food supplements like vitamins, prebiotics, and probiotics. Despite the easy, cheap, safe, and feasible approach to protect patients against acute radiation-induced toxicity, clinical trials have yielded contradictory results. In this review, a detailed overview is given of the various clinical, intestinal manifestations after pelvic irradiation as well as the role of the gut microbiome herein. Furthermore, whilst discussing possible strategies to prevent these symptoms, food supplements are presented as auspicious, prophylactic, and therapeutic options to mitigate acute pelvic radiation-induced GI injury by exploring their molecular mechanisms of action. Full article

Introduction: Se measurement and supplementation in radiation oncology is a controversial issue. The German Working Group Trace Elements and Electrolytes in Oncology (AKTE) has conducted a number of studies on this issue, which are summarized in this review. Strategies have been tested and developed, aiming to stratify the patients with a potential need for supplemental Se and how best to monitor Se supplementation with respect to health effects and risks. Methods: We analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two randomized phase III clinical studies were conducted for testing a potential radioprotective effect of supplemental Se during radiation therapy in patients with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results: A relative Se deficit in whole blood or serum was detected in the majority of tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate cancer). In prostate cancer, tissue Se concentrations were relatively elevated in the carcinoma centre as compared to the surrounding compartment or as compared to tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se supplementation successfully corrected Se-deficiency in the patients analyzed and decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy patients with carcinomas of the uterus. Survival data imply that Se supplementation did not interfere with radiation success. Some positive effects of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy were noted in a second randomized trial in patients with head and neck cancer. We have not observed any adverse effects of supplemental Se in our studies. Conclusions: Se supplementation yielded promising results concerning radioprotection in tumor patients and should be considered as a promising adjuvant treatment option in subjects with a relative Se deficit. Full article

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more and more the attention of both laypersons and expert groups. The interest of oncologists mainly focuses in the following clinical aspects: radioprotection of normal tissues, radiosensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that Se has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas, as well as in the head and neck region, including endolaryngeal edema. Another randomized phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. The aim was to evaluate whether sodium selenite is able to compensate a preexisting selenium deficiency and to prevent radiation induced diarrhea in adjuvant radiotherapy for pelvic gynecologic malignancies. Through this study, the significant benefits of sodium selenite supplementation with regards to selenium deficiency and radiotherapy induced diarrhea in patients with cervical and uterine cancer has been shown for the first time in a prospective randomized trial. Survival data imply that supplementation with selenium does not interfere with the positive biological effects of radiation treatment and might constitute a valuable adjuvant therapy option especially in marginally supplied individuals. More recently there were emerging concerns coming up from two large clinical prevention trials (NPC, SELECT), that selenium increases the possible risk of developing diabetes type II. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantage and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, even if further research is needed. Full article

Curative radiation therapy of pelvic malignancies, frequently results in doselimitingtoxicities such as serous, mucoid, or more rarely, bloody diarrhea. Several studieshave evaluated the cytoprotective effects of amifostine in preventing rectal mucositisassociated with radiation treatment. We searched Medline for published comparativestudies that evaluated the use of amifostine to reduce radiation-induced toxicity associatedwith pelvic irradiation. In ten studies there was an evidence-based cytoprotection (P less than 0.05)by amifostine. Although results are variable, current evidence suggests that amifostine mayhave a radioprotective effect in the rectal mucosa, particularly when administeredintrarectally. Significant improvements were seen in both symptomatic and objective(rectosigmoidoscopy) end points. There is a need to conduct well-designed clinical trialswith sufficient numbers of participants to confirm these findings together with a costbenefitstudy. Objective measurements using rectosigmoidoscopy are superior tosubjective measures such as WHO or RTOG/EORTC toxicity grading scales. Full article