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Vesicular stomatitis virus (VSV) is an oncolytic rhabdovirus and its glycoprotein G is widely used to pseudotype other viruses for gene therapy. Low-density lipoprotein receptor (LDL-R) serves as a major entry receptor for VSV. Here we report two crystal structures of VSV G in complex with two distinct cysteine-rich domains (CR2 and CR3) of LDL-R, showing that their binding sites on G are identical. We identify two basic residues on G, which are essential for its interaction with CR2 and CR3. Mutating these residues abolishes VSV infectivity even though VSV can use alternative receptors, indicating that all VSV receptors are members of the LDL-R family. Collectively, our data suggest that VSV G has specifically evolved to interact with receptor CR domains. These structural insights into the interaction between VSV G and host cell receptors provide a basis for the design of recombinant viruses with an altered tropism. Glycoprotein G of vesicular stomatitis virus (VSV) enables viral entry by binding to the major VSV receptor LDL-R. Here the authors present crystal structures of G in complex with two distinct CR domains of LDL-R, identifying structural determinants for VSV infectivity in mammalian and insect cells.

Vesicular stomatitis virus (VSV), comprising vesicular stomatitis New Jersey virus (VSNJV) and vesicular stomatitis Indiana virus (VSIV), emerges from its focus of endemic transmission in Southern Mexico to cause sporadic livestock epizootics in the Western United States. A dearth of information on the role of potential arthropod vectors in the endemic region hampers efforts to identify factors that enable endemicity and predict outbreaks. In a two-year, longitudinal study at five cattle ranches in Chiapas, Mexico, insect taxa implicated as VSV vectors (blackflies, sandflies, biting midges, and mosquitoes) were collected and screened for VSV RNA, livestock vesicular stomatitis (VS) cases were monitored, and serum samples were screened for neutralizing antibodies. VS cases were reported during the rainy (n = 20) and post-rainy (n = 2) seasons. Seroprevalence against VSNJV in adult cattle was very high (75–100% per ranch) compared with VSIV (0.6%, all ranches). All four potential vector taxa were sampled, and VSNJV RNA was detected in each of them (11% VSNJV-positive of 874 total pools), while VSIV RNA was only detected in four pools of mosquitoes. Our findings indicate that VSNJV is the dominant serotype across our sampling sites with a variety of potential insect vectors involved in its transmission throughout the year. Although no livestock cases were reported in Chiapas during the dry season, VSNJV was detected in insects during this period, suggesting that mechanisms other than transmission from livestock support VSV endemicity.

Interferons induce cell-intrinsic responses associated with resistance to viral infection. To overcome the suppressive action of interferons and their effectors, viruses have evolved diverse mechanisms. Using vesicular stomatitis virus (VSV), we report that the host cell N6-adenosine messenger RNA (mRNA) cap methylase, phosphorylated C-terminal domain interacting factor 1 (PCIF1), attenuates the antiviral response. We employed cell-based and in vitro biochemical assays to demonstrate that PCIF1 efficiently modifies VSV mRNA cap structures to m⁷Gpppm⁶Am and define the substrate requirements for this modification. Functional assays revealed that the PCIF1-dependent modification of VSV mRNA cap structures is inert with regard to mRNA stability, translation, and viral infectivity but attenuates the antiviral effects of the treatment of cells with interferon-β. Cells lacking PCIF1 or expressing a catalytically inactive PCIF1 exhibit an augmented inhibition of viral replication and gene expression following interferon-β treatment. We further demonstrate that the mRNA cap structures of rabies and measles viruses are also modified by PCIF1 to m⁷Gpppm⁶Am. This work identifies a function of PCIF1 and cap-proximal m⁶Am in attenuation of the host response to VSV infection that likely extends to other viruses.

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.

Omega-3 (ω-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received ω-3–rich enteral nutrition (EN; n = 31) or ω-3–poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of ω-3 fatty acids was 900 mg in the ω-3–rich group and 250 mg in the ω-3–poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers. The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the ω-3–rich group, than in the ω-3–poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the ω-3–rich group than in the ω-3–poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the ω-3–rich group than in the ω-3–poor group (P = 0.012 and P = 0.015, respectively). ω-3–rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the ω-3–poor EN support. •Little is known about the effect of ω-3 fatty acids on reducing chemotherapy-related toxicities.•A randomized study was conducted to compare ω-3–rich enteral nutrition (EN) with ω-3–poor EN in patients undergoing cisplatin-based chemotherapy.•ω-3–rich EN reduced the incidence of chemotherapy-related mucosal toxicities and had a hepatoprotective effect during chemotherapy.

Recurrent aphthous stomatitis (RAS), a major type of stomatitis, can significantly impair quality of life. The therapeutic and preventive effects of glycyrrhizin (GL), a compound known for its anti-inflammatory properties, remain unclear due to the lack of appropriate animal models, especially for prevention studies. Therefore, this study aimed to evaluate the therapeutic and preventive effects of GL and determine the optimal concentrations using two hamster models (stomatitis-initiation model and stomatitis-healing model) representing the initiation and healing phases of RAS. The effects were evaluated through macroscopic and histological analyses, gene expression profiling in hamster buccal tissues, and prostaglandin E 2 (PGE 2 ) assays in lipopolysaccharide-stimulated human oral keratinocytes. In the stomatitis-healing model, a low concentration of GL (0.0065%) significantly increased the cure rate and histologically reduced the numbers of vessels and lymphocytes. In the stomatitis-initiation model, low concentrations of GL (0.0065% and 0.033%) significantly decreased the edema score and histologically reduced the numbers of vessels and neutrophils, as well as the mRNA expression levels of interleukin-6 and cyclooxygenase-2 . In contrast, a high concentration of GL (0.33%) showed inferior efficacy compared with low concentrations in both models. Similarly, in LPS-stimulated human oral keratinocytes, low GL concentrations suppressed PGE₂ protein expression, while the highest concentration increased it. These findings show that GL promotes healing and prevents the onset of stomatitis at specific concentrations, underscoring the importance of optimal dosing and supporting the potential clinical application of GL in the management of RAS.

Background Accurate diagnosis of oral mucositis (OM) is essential for effective management and plays a critical role in ensuring reliable outcomes in clinical trials evaluating OM-prevention and treatment strategies. Currently, no evidence-based guidelines specify which clinical profession should be primarily responsible for OM assessments in patients undergoing high-dose chemotherapy. In most Scandinavian countries, nurses perform daily OM assessments, while dentists specialized in orofacial medicine (considered the gold standard) conduct supplementary evaluations several times per week. However, the concordance between nurses’ assessments and those conducted by dentists specialized in orofacial medicine remains unclear. Therefore, this study aimed to evaluate the interrater reliability in of OM assessments between these two professions. Methods This study utilized data from a randomized, blinded, multicenter, parallel-group, phase 3 trial conducted at five university hospitals in Sweden and Norway. A total of 127 patients aged 18 years or older, diagnosed with multiple myeloma or lymphoma, and scheduled to receive high-dose conditioning chemotherapy in preparation for hematopoietic stem cell transplantation, were included. The primary objective was to evaluate the interrater reliability of OM assessments across all severity grades using the World Health Organization (WHO) oral toxicity scale (grades 0–4). The secondary objective was to evaluate the interrater reliability of OM assessments across all severity grades at each individual study site. Results Overall interrater reliability between nurses and dentists specialized in orofacial was found to be fair for OM of any grade (κ = 0.211, p  < 0.001). However, agreement levels at individual study sites ranged from no agreement to fair agreement. Conclusion The interrater reliability in the assessment of oral mucositis between dentists specialized in orofacial medicine and nurses ranged from no-, to fair agreement. This highlights the need for targeted interventions to improve nurses' assessment skills or to integrate a specialized dentist as a permanent member of the multidisciplinary team in oncology and hematology settings. Trial registration This study is based on data from a previously registered clinical trial (ClinicalTrials.gov; Identifier: NCT03203733, Registered on November 20, 2020).

Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target. A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment. There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm. Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study.

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus-based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus-based vaccines will each require extensive analysis to optimize stabilizing formulations.

Purpose Considering the complex pathobiology of oral mucositis, especially in oral cancer patients, the prevention and treatment of oral mucositis in patients undergoing radiotherapy remains an essential and clinically crucial unmet need. The present study aims to investigate and compare the effects of synbiotic mouthwash with normal saline mouthwash on the prevention and control of radiotherapy-induced oral mucositis in oral cancer patients. Methods Double-blind, randomized clinical trial (RCT) performed on 64 oral cancer patients who underwent radiotherapy (IRCT20201106049288N1, registration date: 2020–12-23). Patients were divided randomly into the case (32 subjects) and control (32 subjects) groups. All patients underwent intensity-modulated radiotherapy and received 6000 cGY of radiotherapy in 34 fractions. All patients received the usual treatment for mucositis, but in the case group, synbiotic mouthwash was prescribed and in the control group, normal saline mouthwash was prescribed from a day before the start to the end of radiotherapy treatment. Patients were monitored every session for 6 weeks to check the progression, oral involvement severity, and mucositis grade. Results The case group showed a significant reduction in the oral mucositis severity. The mucositis grade in the case group from the 7th session of oral examination was significantly lower than the control ( p  < 0.05), and this significant difference persisted until the last session of oral examination. Incidence rates of severe oral mucositis (grade 3) during the treatment period were 11.59% in the case and 36.45% in control ( p  < 0.001). Conclusion Synbiotic mouthwash significantly reduces and prevents oral mucositis intensity in oral cancer patients undergoing radiotherapy.