Immunological Classification of Pancreatic Carcinomas to Identify Immune Index and Provide a Strategy for Patient Stratification

BackgroundCancer immunotherapy has produced significant positive clinical effects in a variety of tumor types. However, pancreatic ductal adenocarcinoma (PDAC) is widely considered to be a “cold” cancer with poor immunogenicity. Our aim is to determine the detailed immune features of PDAC to seek new treatment strategies.MethodsThe immune cell abundance of PDAC patients was evaluated with the single-sample gene set enrichment analysis (ssGSEA) using 119 immune gene signatures. Based on these data, patients were classified into different immune subtypes (ISs) according to immune gene signatures. We analyzed their response patterns to immunotherapy in the datasets, then established an immune index to reflect the different degrees of immune infiltration through linear discriminant analysis (LDA). Finally, potential prognostic markers associated with the immune index were identified based on weighted correlation network analysis (WGCNA) that was functionally validated in vitro.ResultsThree ISs were identified in PDAC, of which IS3 had the best prognosis across all three cohorts. The different expressions of immune profiles among the three ISs indicated a distinct responsiveness to immunotherapies in PDAC subtypes. By calculating the immune index, we found that the IS3 represented higher immune infiltration, while IS1 represented lower immune infiltration. Among the investigated signatures, we identified ZNF185, FANCG, and CSTF2 as risk factors associated with immune index that could potentially facilitate diagnosis and could be therapeutic target markers in PDAC patients.ConclusionsOur findings identified immunologic subtypes of PDAC with distinct prognostic implications, which allowed us to establish an immune index to represent the immune infiltration in each subtype. These results show the importance of continuing investigation of immunotherapy and will allow clinical workers to personalized treatment more effectively in PDAC patients.

Harnessing Intranasal Delivery Systems of Sumatriptan for the Treatment of Migraine

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.

Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review

Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.

Investigating Toxin Diversity and Abundance in Snake Venom Proteomes

Understanding snake venom proteomes is becoming increasingly important to understand snake venom biology, evolution and especially clinical effects of venoms and approaches to antivenom development. To explore the current state of snake venom proteomics and transcriptomics we investigated venom proteomic methods, associations between methodological and biological variability and the diversity and abundance of protein families. We reviewed available studies on snake venom proteomes from September 2017 to April 2021. This included 81 studies characterising venom proteomes of 79 snake species, providing data on relative toxin abundance for 70 species and toxin diversity (number of different toxins) for 37 species. Methodologies utilised in these studies were summarised and compared. Several comparative studies showed that preliminary decomplexation of crude venom by chromatography leads to increased protein identification, as does the use of transcriptomics. Combining different methodological strategies in venomic approaches appears to maximize proteome coverage. 48% of studies used the RP-HPLC →1D SDS-PAGE →in-gel trypsin digestion → ESI -LC-MS/MS pathway. Protein quantification by MS1-based spectral intensity was used twice as commonly as MS2-based spectral counting (33–15 studies). Total toxin diversity was 25–225 toxins/species, with a median of 48. The relative mean abundance of the four dominant protein families was for elapids; 3FTx–52%, PLA2–27%, SVMP–2.8%, and SVSP–0.1%, and for vipers: 3FTx–0.5%, PLA2–24%, SVMP–27%, and SVSP–12%. Viper venoms were compositionally more complex than elapid venoms in terms of number of protein families making up most of the venom, in contrast, elapid venoms were made up of fewer, but more toxin diverse, protein families. No relationship was observed between relative toxin diversity and abundance. For equivalent comparisons to be made between studies, there is a need to clarify the differences between methodological approaches and for acceptance of a standardised protein classification, nomenclature and reporting procedure. Correctly measuring and comparing toxin diversity and abundance is essential for understanding biological, clinical and evolutionary implications of snake venom composition.

SARS-CoV-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and mortality rates, particularly in the first world. In late 2021, the Omicron (B.1.1.529) virus variant emerged, with significant genetic differences and clinical effects from other variants of concern (VOC). This variant a demonstrated higher number of polymorphisms in the gene encoding the Spike (S) protein, and there has been displacement of the dominant Delta variant. We assessed the impact of Omicron infection on the ability of: serum from vaccinated and/or previously infected individuals; concentrated human IgG from plasma donors, and licensed monoclonal antibody therapies to neutralise the virus in vitro. There was a 17 to 27-fold reduction in neutralisation titres across all donors who had a detectable neutralising antibody titre to the Omicron variant. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 16-fold. Of all therapeutic antibodies tested, significant neutralisation of the Omicron variant was only observed for Sotrovimab, with other monoclonal antibodies unable to neutralise Omicron in vitro. These results have implications for ongoing therapy of individuals infected with the Omicron variant.

Measurement of the Clinical Effects of a Marine Fish Extract on Periodontal Healing—A Preliminary Clinical Interventional Study

The aim of the study was to assess the clinical effects of periodontal healing using a Romanian pharmaceutical compound of marine fish extract (Alflutop®). Adults with periodontal disease were included in the study group. Gingival inflammation, the degree of tooth mobility, and probing depth (PD) were recorded for each patient before and after therapy. Patients were divided into two groups: group I—after scaling and root planing (SRP), patients followed therapy with marine fish extract, Alflutop®, group II—SRP therapy alone. Statistically significant differences between groups in terms of gingival inflammation reduction (p = 0.045) were found. Tooth mobility reduction, as well as PD improvement, were also noticed after the therapy (p = 0.001), but no statistically significant differences among PD reduction rates were found (p = 0.356). Alflutop® has proven a certain therapeutic efficiency in the treatment of periodontitis in terms of reduction in the clinical signs of inflammation and tooth mobility.

Posterior Laminectomy and Lateral Mass Screw Fixation for the Treatment of Severe Cervical Spondylotic Myelopathy

Background Severe and complex cervical spondylotic myelopathy(CSM) requires surgical treatment. The common methods of posterior cervical spine surgery are laminoplasty and laminectomy with lateral mass screw internal fixation. However, the operative effect of this surgical approach is unclear owing to the complexity and severity of CSM in patients who undergo this surgical treatment.Therefore, we aimed to evaluate the clinical effects of posterior cervical laminectomy and lateral mass screw internal fixation in patients with severe and complex CSM. Methods We retrospectively analysed 60patients (48men,12women; mean age59.7 years) with severe and complex CSM who underwent posterior cervical laminectomy and lateral mass screw internal fixation from May 2013 to June 2020. Forty-eight patients underwent laminectomy and lateral mass screw internal fixation;12 patients underwent laminectomy and lateral mass screw internal fixation with 1–2 segmental laminoplasty. C-spine radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) were used to detect any curvature and fusion of the cervical spine, restenosis, and loose/broken internal fixation screws.Clinical efficacy was evaluated using Japanese Orthopaedic Association (JOA)scores, neck disability index(NDI), Odom’s classification, and the visual analogue scale(VAS) for pain. Results Overall effect was satisfactory at the last follow-up (average, 3.6 years [range, 6 months–6 years]), with no restenosis or loosened, slipped, or broken internal fixations. The anterior curvature angle of lordosis (n=46)was not significantly different from baseline at the last follow-up(P>0.05). The cervical kyphosis angle (n=14)was significantly improved at the last follow-up compared with the baseline value (P<0.05), as were the JOA, NDI, and VAS scores(all P<0.05). Odom’s classifications at the last follow-up were excellent, good, and fair in 45, 12, and three patients, respectively. Conclusions Posterior cervical laminectomy and lateral mass screw internal fixation achieved satisfactory clinical results in severe and complex CSM cases.Combining this surgical method with laminoplasty of 1–2 spinal segments stabilised the cervical spine and provided spinal decompression while preventing excessive backward drift of the cervical spinal cord, resulting in fewer complications.