Search Results (95)

Background: Previous studies have shown Radix Hedysari (RH)’s gastroprotective potential, but its active components and mechanisms remain uncharacterized. This study aimed to identify RH’s bioactive fractions, elucidate protection mechanisms, establish flavonoid dose-effect relationships, and determine the pharmacodynamic basis. Methods: Chemical profiling quantified eight flavonoids via HPLC. Network pharmacology screened targets/pathways using TCMSP, GeneCards databases. In vivo validation employed cisplatin–induced injury models in Wistar rats (n = 10/group). Assessments included: behavioral monitoring; organ indices; ELISA (MTL, VIP, IFN–γ, IgG, IL–6, TNF–α etc.); H&E; and Western blot:(SCF, c–Kit, p65). Dose–effect correlations were analyzed by PLS–DA. Results: Content determination indicated that Calycosin–7–glucoside and Ononin were notably enriched on both the n–BuOH part and the EtOAc part. Network pharmacology identified 5 core flavonoids and 8 targets enriched in IL–17/TNF signaling pathways. n–BuOH treatment minimized weight loss vs. MCG, increased spleen/thymus indices. n–BuOH and HPS normalized gastrointestinal, immune, inflammatory biomarkers (p < 0.01 vs. MCG). Histopathology confirmed superior mucosal protection in n–BuOH group vs. MCG. Western blot revealed n–BuOH significantly downregulated SCF, c–kit, and p65 expressions in both gastric and intestinal tissues (p < 0.001 vs. MCG). PLS–DA demonstrated Calycosin–7–glucoside had the strongest dose–effect correlation (VIP > 1) with protective outcomes. Conclusions: The n–BuOH fraction of RH is the primary bioactive component against chemotherapy–induced gastrointestinal injury, with Calycosin–7–glucoside as its key effector. Protection is mediated through SCF/c–Kit/NF–κB pathway inhibition, demonstrating significant dose–dependent efficacy. These findings support RH’s potential as a complementary therapy during chemotherapy. Full article

Background: Cachexia worsens prognosis, quality of life and chemotherapy treatment compliance of patients with lung cancer. Chemotherapy-induced cachexia has also been implicated in lowered mortality. This study aimed to evaluate the frequency of cachexia-related measures and symptoms as outcomes in lung cancer chemotherapy trial protocols and to examine how key trial characteristics influence them. Method: We conducted a cross-sectional data analysis of randomised controlled chemotherapy trials of lung cancer registered in four public trial registries between 2012 and 2023. Trial outcome measures included overall survival, treatment toxicity/side effects and cachexia-related indicators such as physical activity, weight/body mass index (BMI), dietary limitations, caloric intake and lean muscle mass. Symptom-related outcomes, including appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, dysphagia, dyspnoea and oral mucositis, were also extracted. Additionally, the number and type of performance status and assessment tool were recorded. Data were summarised descriptively. Chi-square tests were used to examine associations between trial outcomes and characteristics including cancer type, trial location, lead investigator/funding source, assessment tools and trial commencement year. A p < 0.05 was considered statistically significance. Results: Of the 335 trial protocols (non-small cell (87.2%) and small cell (12.8%)), most were from Europe (50.4%). The trial lead investigator was from industry (56.7%) followed by academia (25.1%). Allied health professional involvement was minimal (0.6%). Trial protocols mostly recorded overall survival (96.4%) and toxicity (83.9%). However, physical activity, weight/BMI, dysphagia, dyspnoea and oral mucositis were recorded in <30%, with dietary limitations, caloric intake and lean muscle mass recorded in <3% of the trials. Measures and symptoms were not associated with cancer type. Trial location was associated with the measures toxicity, physical activity and caloric intake and all symptoms. Lead investigator was associated with the measures toxicity and weight/BMI and all symptoms except for dyspnoea. Performance status and assessment tools were mentioned in 93.4% and 41.8% of the trials, respectively, with significant associations between assessment tools and outcomes, except for weight/BMI, dietary limitations, lean muscle mass, dysphagia and oral mucositis. There was a significant trend with trial commencement year for the measures physical activity (p = 0.002) and weight/BMI (p = 0.000) and all symptoms, except for appetite loss (p = 0.115) and pain (p = 0.433). Conclusions: While the reporting of measures and outcomes was generally higher compared to gastrointestinal chemotherapy cancer trials, it still faced significant under-reporting. Assessment tools should include cachexia-specific symptoms to accurately assess the quality of life in patients with lung cancer undergoing chemotherapy clinical trials. Full article

Cisplatin (CDDP) is an anticancer drug that is frequently used to treat head and neck cancers; however, it may cause oral mucositis. The discontinuation of CDDP may be required for some patients with a severe status, and the control of oral mucositis is extremely important. β-Cryptoxanthin (β-cry), a carotenoid, exerts anti-inflammatory effects. Its inhibition of 5-FU-induced inflammatory responses was recently demonstrated. However, the effects of β-cry on CDDP-induced oral mucositis remain unclear. In the present study, we stimulated human oral mucosa-derived keratinocytes (hOMK) and fibroblasts (hOMF) with CDDP, added β-cry, and examined its effects, with a focus on the production of inflammatory cytokines, matrix metalloproteinase (MMPs), and reactive oxygen species (ROS). CDDP increased the mRNA expression and production of inflammatory cytokines and MMPs both in hOMK and hOMF. However, increases in IL-6 and MMP-9 mRNA expression levels and IL-6 production in CDDP-treated hOMK and hOMF were inhibited by β-cry. Furthermore, the production of ROS and the rate of SA-β-gal-positive cells were increased by CDDP, but were not affected by β-cry. CDDP may induce oral mucositis by increasing the levels of inflammatory cytokines, MMPs, and ROS. β-cry partially inhibited CDDP-induced increases in inflammatory cytokines and MMPs, suggesting its potential to attenuate the symptoms of chemotherapy-related oral mucositis. Full article

The human papillomavirus type 16 (HPV 16) is a high-risk human papillomavirus strain commonly associated with oropharyngeal cancers, including lymph node involvement. The treatment for HPV 16-related tonsil cancer, commonly involving surgery, radiation, and chemotherapy, presents significant challenges. Complications such as oral mucositis, xerostomia, dysphagia, dysgeusia, hypogeusia, impaired gustatory function, and significant weight loss frequently arise, leading to reduced nutritional intake, impaired healing, and recovery progression. These challenges underscore the need for supportive interventions to enhance rehabilitation and the post-recovery period, improve treatment tolerance, and maintain quality of life. Objective: This single-subject study examines a 67-year-old male patient diagnosed with a T1N3b (small primary tumor with advanced lump node involvement) associated with HPV 16 positivity, indicating a virus-associated oncogenesis. Methods: The patient underwent radiation therapy and chemotherapy, leading to treatment-associated side effects. After having dietary drinks for daily nourishment, the patient routinely incorporated oral bio extra virgin olive oil (BEVOO) to cope with indicated challenges. Results: Body composition and metabolic parameters showed treatment-induced declines, followed by substantial but not complete recovery during follow-up examination. Visual Analog Scale (VAS) scores reflected gradual improvements in dysphagia, xerostomia, mucositis, and subtle but ongoing enhancement of the dysgeusia, gustatory perception, and oral palatability. The BEVOO supplementation and mindfulness were associated with positive recovery trends. Additional variables could have impacted the outcomes, preceding and throughout treatment, including the patient’s cognitive and somatic health, environmental conditions, dietary habits, individual attitudes toward recovery, physical activity, and patient way of life. Conclusions: These results emphasize the need for additional research employing a comprehensive, multi-factorial framework that accounts for the complex interplay of physiological, psycho-social, and environmental contributors. More extensive, more diverse studies are essential to confirm these observations and substantiate the role of BEVOO as a supportive intervention in cancer recovery. Full article

Sanghuang (Sanghuangporus sanghuang, SS) is a medicinal fungus with multiple pharmacological effects, including antioxidant, anti-inflammatory, immune-boosting, and anti-cancer activities. 5-fluorouracil (5-FU) is a commonly used chemotherapeutic agent for the treatment of colorectal cancer. It primarily exerts its antitumor effect by inhibiting DNA and RNA synthesis, leading to cell apoptosis. However, it frequently induces adverse effects These issues limit the clinical application of 5-FU. This research aims to determine the potential of SS as a therapeutic agent in reducing 5-FU-induced intestinal mucositis in a mouse model. The results indicated that 5-FU administration significantly increased diarrhea severity, reduced colon length, caused small intestinal villus atrophy, disrupted intestinal architecture, led to insufficient crypt cell proliferation, and resulted in weight loss. It also significantly upregulated inflammatory responses, apoptosis, oxidative stress, and epithelial–mesenchymal transition (EMT) pathways, and disrupted the integrity of intestinal mucosal tight junction, while elevating pro-inflammatory cytokines and reducing antioxidant capacity. However, SS significantly ameliorating alleviating the adverse impacts of the chemotherapeutic agent on the intestinal mucosa. In conclusion, this investigation provides the first evidence of the protective effects of SS on 5-FU-induced mucositis. These findings suggest SS as a potential therapeutic application, offering a promising strategy for reducing the adverse effects of 5-FU chemotherapy and improving the treatment and quality of life for colorectal cancer patients. Full article

Objectives: Mucositis is a debilitating side effect of cancer therapy that adversely affects quality of life, cost of care, and the outcome of cancer therapy. Oral mucositis-related pain may be treated with numerous modalities but often includes opioids. The effects of opiate treatment on painful UM and its overall influence on the burden of illness (BOI) in cancer patients remain unknown. Methods: This study utilized the 2017 United States (US) National Inpatient Sample (NIS) database. The exposure was opioid treatment for chemo-induced ulcerative mucositis (UM), oral mucositis-induced pain, and the main outcomes included in-hospital mortality and BOI, length of hospital stays (LOS), and total hospital charges. Multivariable regression analysis was used to examine the relationship between outcomes and the key independent variable, opioid use, adjusting for propensity scores. Results: In the propensity score-adjusted analysis, UM patients with opioid treatment had 0.51 times lower total charges (95% CI: 0.42–0.76) and 0.67 times shorter LOS (95% CI: 0.51–0.87) than the UM patients without opioid treatment. However, there was no association between opioid treatment and in-hospital mortality. In the sensitivity analysis, the effect estimates were comparable in the propensity score-adjusted analysis, the decile-adjusted model, and the full model with the non-propensity score estimated method. Conclusions: Cancer patients with chemotherapy-induced UM-prescribed opioid analgesics for treating pain are associated with a lower BOI. Opioid pain medications are commonly provided to cancer survivors; estimating the BOI among them is crucial in supportive care research. Full article

Background/Objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5–fluorouracil (5–FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. Camellia tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5–FU-induced ferroptosis and inflammation in human keratinocytes. Methods: HaCaT cells were induced by 5–FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX–4) activity, as well as IL–6, IL–1β, and TNF–α levels, and their wound healing properties were assessed. Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5–FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX–4 activity. Additionally, it suppressed the cytokine production of 5–FU-induced cells in a concentration–dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5–FU damage significantly and dose dependently. Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5–FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis. Full article

Chemotherapy using anticancer agents and radiotherapy of cancers frequently induce the development of stomatitis as a side effect. In the present study, hydrogels for effective stomatitis healing under anticancer drug administration were developed using three components, namely proline, carboxyvinyl polymer, and water (denoted proline gels). Characterization including tilting, Fourier transform infrared spectra, and viscoelasticity measurements indicated that proline gels with proline concentrations over 300 μmol/g could retain water on the tongue of mice. The degradation and release behavior of proline gels in serological environments were evaluated, revealing that proline gels were degraded by serological salt concentrations, and the cumulative amount of proline released from proline gels depended on the concentration of proline in the gel. Proline gels were applied to the stomatitis area on the tongue of mice under anticancer drug administration, with subsequent reduction in the stomatitis area and regeneration of the mucosal epithelium layer, demonstrating effective stomatitis healing by proline gels with proline concentrations over 500 μmol/g. Other control samples including the carboxyvinyl polymer or proline alone did not reduce the stomatitis area in model mice. These results suggested that the proline gel is promising for the mucosa regeneration of anticancer drug-induced stomatitis. Full article

Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice. Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5× was compared to the commercial product Dentoxol^®. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol^® reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol^®, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol^® group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol^®. Full article

Background/Objectives: Oral mucositis (OM) is the most common acute complication among cancer patients. It initially manifests as an inflammatory process, beginning with erythema and edema of the oral mucosa, progressing to erosive lesions, and ultimately leading to highly painful ulcers. This systematic review seeks to evaluate the efficacy of preventive PBM protocols in mitigating chemotherapy-induced OM. Methods: The PRISMA guidelines were followed. The search was conducted in August 2024 in the following databases: Pubmed/Medline, Scopus, WoS, Cochrane, SciELO, BDTD, and BVS/IBECS. Only randomized clinical trials that utilized preventive photobiomodulation protocols in chemotherapy patients were included. All studies involving patients previously treated with radiation therapy were excluded. The Joanna Briggs Institute tool was employed for risk of bias analysis. Results: The total sample size consisted of 828 patients aged between 1 and 84 years. There was no predisposition based on gender or age. When the patients were evaluated under preventive protocols, some cases of mucositis manifested in a total of 339 cases. Of the total number of patients in the 13 selected studies (n = 828), 40.94% developed oral mucositis over the course of chemotherapy cycles. Comparing the experimental and control groups, 211 patients who did not receive preventive laser treatment developed oral mucositis; in contrast, only 128 in the experimental group did. Eighty-five percent of the studies exhibited a low risk of bias. Conclusions: Preventively applied photobiomodulation proves effective in minimizing or even preventing the manifestation of oral mucositis and reducing the severity of lesions that arise during oncological treatment. Registration PROSPERO (CRD42023465329). Full article

Leukemias and lymphomas, encompassing a spectrum of hematologic malignancies, often exhibit manifestations in various tissues and organs, including the ears, nose, and throat (ENT) region, extending beyond the typical sites of bone marrow and lymph nodes. This manuscript explores these interactions, considering disease-related symptoms and treatment effects. ENT symptoms, such as otalgia, hearing loss, and nasal obstruction, may arise from direct infiltration or treatment complications, with chemotherapy-induced ototoxicity being particularly characteristic. Furthermore, immunotherapy complications, including cytokine release syndrome and mucosal irritation, can also contribute to ENT symptoms. Additionally, targeted therapy and radiotherapy can lead to mucosal dryness, dysphonia, and radiation-induced otitis media. Patients with hematologic malignancies are especially vulnerable to various ENT infections, including bacterial, viral, and fungal infections, due to compromised immunity resulting from both the disease and its treatments. Conditions such as rhinosinusitis, otitis media, and pharyngitis pose significant management challenges. Moreover, patients undergoing hematopoietic stem cell transplantation (HSCT) face unique ENT considerations, including mucositis, opportunistic infections, and graft-versus-host disease in cases of allogeneic HSCT. These patients require specialized pre-transplant evaluations, meticulous post-transplant surveillance, and tailored assistance to mitigate complications. This manuscript underscores the importance of a multidisciplinary approach that integrates diagnostics, pharmacological interventions, and supportive care to address both disease-related and treatment-induced ENT manifestations. Further research is needed to refine management strategies and improve outcomes in this complex clinical population. Full article

5-Fluorouracil (5-FU) is an antimetabolite widely prescribed in cancer treatments, but its use in highly proliferative tissues can cause significant problems such as mucositis. Bacillus clausii is a probiotic commonly used for protection against acute diarrhea, gastrointestinal dysbiosis and inflammatory bowel diseases. We investigated the effect of B. clausii on 5-FU intestinal mucositis in mice. B. clausii was administered concomitantly with 5-FU on the first day and alone for the other two days. After the third day of 5-FU (450 mg/kg, ip), the animals were euthanized. Ileum samples were removed for evaluation for histopathological and biochemical analyses (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). In addition, we investigated gastric emptying and intestinal transit, intestinal permeability, intestinal smooth muscle contractility, transepithelial electrical resistance and intestinal transport of water and electrolytes. B. clausii reduced histopathological scores and increased the villus/crypt ratio in all intestinal segments after mucositis. B. clausii attenuated 5-FU-induced weight loss. The probiotic treatment increased GSH levels, reduced MPO and CAT activity, and also reduced MDA, IL-1β and TNF-α levels. B. clausii attenuated the delay in gastric emptying, water and electrolyte secretion and intestinal hypercontractility, and increased 5-FU-induced intestinal permeability. Thus, our data suggest that B. clausii may be a potential candidate for the treatment of chemotherapy-induced intestinal mucositis. Full article

5-Fluorouracil (5-Fu) is a chemotherapeutic agent widely used to treat various cancers, which causes intestinal mucositis as a common side effect. Ginsenoside Rc, an active compound with anti-inflammatory, antioxidant, immunomodulatory, and antitumor properties, has protective effects against chemotherapy-induced mucositis caused by 5-Fu. This study aims to evaluate the protective effects of Rc on 5-Fu-induced chemotherapy-related mucositis and to elucidate its underlying mechanisms. In vivo experiments were conducted to measure intestinal permeability and assess the effects of Rc on body weight loss, diarrhea, and intestinal pathology induced by 5-Fu. Network pharmacology was also employed to explore potential mechanisms. In vitro, IEC-6 cell models were used to validate the cytoprotective effects of Rc, including assessments of cell viability, apoptosis, lactate dehydrogenase (LDH) release, and changes in inflammatory cytokine levels. The results indicate that Rc significantly ameliorated body weight reduction, diarrhea, and intestinal damage in mice treated by 5-Fu. Rc significantly mitigated 5-Fu-induced cellular damage by reducing levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α and decreasing apoptosis and cell permeability. Western blot analysis revealed that Rc upregulated the expression of Bcl-2 and tight junction proteins and downregulated the expression of Bax. Furthermore, Rc exerts anti-inflammatory and anti-apoptotic effects through PI3K-AKT and NF-κB signaling pathways. In conclusion, ginsenoside Rc demonstrated significant protective effects against 5-Fu-induced intestinal mucositis via the PI3K-AKT/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for chemotherapy-related mucositis. Full article

Sodium–glucose co-transporter 1 (SGLT1) is primarily expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines, where it mediates the unidirectional absorption of glucose and galactose. Beyond its well-established role in nutrient absorption, SGLT1 also plays a protective role in maintaining the integrity of the intestinal barrier. Specifically, the natural ligand of SGLT1 (d-glucose) and a synthetic C-glucoside developed by our group can induce a protective anti-inflammatory effect on the intestinal epithelium. In this paper, we report the creation of a small library of C-glycoside, putative ligands for SGLT1, to gain further insights into its unclear mechanism of action. Preliminary biological experiments performed on an in vitro model of doxorubicin-induced mucositis, a severe intestinal inflammatory condition, indicate that the aromatic moiety present in all the compounds of the library is crucial for biological activity, while the sugar component appears to have less influence. These findings will be exploited to develop new, more potent anti-inflammatory compounds and to better understand and rationalize the protective mechanism of action. Full article

Oral mucositis associated with candidiasis can causes systemic candidemia, posing a risk to cancer patients administered antineoplastic therapy. Cold atmospheric pressure plasma jets (CAPPJs) have antifungal and anti-inflammatory properties. This study evaluated the effects CAPPJs in preventing systemic fungal dissemination in a murine model of oral mucositis associated with candidiasis. Forty Wistar rats were divided into groups: CAPPJs (treated) and non-treated controls (for comparison), with subgroups subject to 24 and 72 h of treatment (n = 10 each). Four cycles of chemotherapy (cisplatin and 5-fluorouracil (5-FU)) were administered, followed by oral inoculation of Candida albicans for 3 days. Mucosal damage was induced on the lateral side of tongue with 50% acetic acid. CAPPJ treatment was performed on the lesion for 5 min (2 days). Body weight was assessed daily. Fungal dissemination was conducted using organ macerates and plated on Sabouraud Agar with chloramphenicol. Blood samples were obtained for blood count tests. Chemotherapy affected the general health of the animals, as evidenced by body weight loss. Treatment with CAPPJs showed an inhibitory effect on C. albicans, with a significant reduction in fungal recovery from the tongue after 24 h (p < 0.05). Interestingly, systemic fungal dissemination was significantly reduced after 24 and 72 h of treatment when compared to control (p < 0.05). Taken together, these results suggest that CAPPJs have potential for clinical application in patients with oral mucositis at risk of candidemia. Full article