Systemic Immune Responses Research Articles

Immunological and Biochemistry Comparative Studies of COVID-19, Vaccinated, and Healthy Individuals

Insufficient information on the immune response to the Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2), an essential component in developing effective vaccines and therapies, is a critical issue. Consequently, establishing clinical methods for evaluating immune responses to the SARS-CoV-2 virus and validating the direct participation of the parameters in the development of adaptive immune responses are necessary. Furthermore, a comprehensive guide to the diseases caused by the novel SARS-CoV-2 coronavirus is critical. Employing universal and non-specific early cytokines, specifically, interferon-gamma (IFN-γ) in immune clinics during immune response assessments, presents potential in several respects. IFN-gamma promotes the production of other antiviral molecules and stimulates immune system responses against the virus. Nonetheless, reports indicated that some individuals with severe COVID-19 exhibited impaired IFN-gamma production, which might contribute to the severity of the illness. Enhancing IFN-gamma synthesis or exogenous IFN-gamma therapy has demonstrated potential as a COVID-19 treatment approach. Significant IL-6 levels are associated with cytokine storm progression, which denotes excessive and uncontrolled immune responses that could lead to tissue damage. Targeting IL-6 with specific inhibitors, such as monoclonal antibodies, could reduce COVID-19 severity in certain patients. The results obtained in this study indicated that blood electrolytes and immune variable levels (interleukin 6 and IFN-gamma) were significantly different among the infected, vaccinated, and control groups.

Comprehensive pan-cancer analysis of FUTs family as prognostic and immunity markers based on multi-omics data

BackgroundThe dysregulation of fucosyltransferases (FUTs) contributes to alterations in fucosylated epitope expression, which serve as distinctive features of cancer cells. Nonetheless, a comprehensive elucidation of the prognostic biological marker and therapeutic target of the FUTs family in pan-cancer remains elusive.MethodsOver 10,000 individuals' profiling information was examined, including information on 750 small molecule drugs, 33 types of cancer, and 24 types of immune cells. We focused on POFUT2's function and applied GSVA (Gene Set Variation Analysis) to calculate the FUT score. Survival and cancer pathways were found to be correlated with this score. After deriving a signature via univariate Cox and LASSO regression, we generated and analyzed the ROC curve and developed a nomogram.ResultsOur comprehensive analysis revealed epigenetic, genomic, and immunogenomic changes in FUTs, particularly POFUT2, resulting in aberrant expression. Elevated frequencies of CNV (Copy number variation), SNV (Single Nucleotide Variant), and hypermethylation were observed in FUTs. Additionally, the survival of patients with various types of cancers may be predicted by FUT expression. Immune response and prognosis in numerous types of cancer were found to be strongly linked to aberrant POFUT2 expression. Pathway analysis unveiled the role of FUTs in apoptosis, epithelial-to-mesenchymal transition (EMT), cell cycle, DNA damage response, RAS/MAPK, TSC/mTOR, PI3K/AKT, AR, ER, and RTK. A prognostic index for patients diagnosed with adrenocortical carcinoma (ACC) was established by applying a risk model incorporating nine FUTs and based on the findings of the GSVA.ConclusionsFUTs, particularly POFUT2, emerge as candidate targets for improving the outcomes of immune therapy. The significance of aberrant MUC12 expression, cancer immune therapy, and patient survival in the context of diverse malignancies is enhanced by the strong correlation observed among these factors. Our five-gene risk signature provides patients with ACC with an independent prognostic indicator, emphasizing the critical function of these genes in inhibiting the immune system's response in ACC.

Animal Models in COVID-19 Research: Insights and Outcomes

Animal models have been critical in understanding the pathogenesis, transmission, and therapeutic interventions for COVID-19, caused by SARS-CoV-2. The primary challenges include species-specific differences in viral receptor expression, particularly the ACE2 receptor, and immune system responses, which can affect how closely these models mimic human COVID-19 pathology. Additionally, ethical concerns around the use of animals, especially non-human primates, and logistical issues such as high costs, housing requirements, and limited availability of certain models, further complicate research efforts. Transgenic mice expressing human ACE2 (hACE2) are widely used because of their ease of handling and cost-effectiveness. Other animal models include non-human primates, hamsters, cats, and ferrets, which were used to study viral transmission and host-pathogen interactions. The rapid dynamics of the SARSCoV-2 evolution is one of the challenges and the complementary use of multiple models provides a more comprehensive understanding of the disease. Nonetheless, these models have been essential for rapid advancements in COVID19 vaccine and therapeutic development, offering insights that continue to guide public health strategies. The review discusses the various animal models used in SARS-CoV-2 research, the outcomes, and the challenges and questions to be addressed Keywords: Animal models, SARS-CoV-2, COVID-19

A novel outer membrane vesicle adjuvant improves vaccine protection against Bordetella pertussis

Pertussis is a vaccine-preventable respiratory disease caused by the Gram negative coccobacillus Bordetella pertussis. The licensed acellular pertussis (aP) vaccines protect against disease but do not prevent bacterial colonization and transmission. Here, we developed and tested an intranasal vaccine composed of aP antigens combined with T-vant, a novel adjuvant derived from bacterial outer membrane vesicles, that elicits both mucosal and systemic immune responses. We hypothesized that immunization of mice with aP-T-vant would enhance mucosal immunity and eliminate B. pertussis in the respiratory tract. In contrast to mice immunized intramuscularly with the licensed aP vaccine, intranasal immunization with aP-T-vant eliminated bacteria in both the lung and nasopharynx. Protection was associated with IFN-gamma and IL-17-producing, non-circulating CD4 + T cells in the lung and nasopharynx, and sterilizing immunity in the nasopharynx was dependent on IL-17. Novel mucosal adjuvants, such as T-vant, warrant further investigation to enhance the efficacy of next generation pertussis vaccines.

Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica

BackgroundCutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures.MethodsHere we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022.ResultsOur results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test.ConclusionsThe results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL.Graphical abstract

The Prognostication of Surgically Resected Head and Neck Squamous Cell Carcinoma Using Pre-Therapy Neutrophil and Lymphocyte Counts.

Hematological markers, such as neutrophils (ANC), lymphocyte (ALC), and neutrophil-lymphocyte ratio (NLR), may serve as indicators of systemic inflammation and immune response in head and neck squamous cell carcinoma (HNSCC). However, their prognostic significance across HNSCC subtypes remains to be fully elucidated. We conducted a secondary analysis of a randomized clinical trial involving patients with surgically resected HNSCC with either positive margins or extranodal extension. These patients received either adjuvant chemoradiation with or without lapatinib. We explored the correlation between pre-therapy ANC, ALC, and NLR levels and overall survival (OS) as well as disease-free survival (DFS). A sub-group analysis examined potential links between these markers, primary tumor location, and HPV status. Of the 688 patients in the trial, we included 681 patients with documented pre-therapy ANC and ALC values. High pre-therapy ANC and ALC were significantly associated with reduced OS (HR, 1.56; 95% CI: 1.19-2.05) and (HR, 1.34; 95% CI: 1.01-1.79), respectively. High NLR did not significantly affect OS (HR, 1.09; 95% CI: 0.81-1.47). Subgroup analysis indicated significantly reduced OS in patients with high ANC across oropharyngeal, non-oropharyngeal, and HPV-negative subtypes. High ANC, ALC, and NLR did not impact DFS notably. Elevated pre-therapy ANC is strongly associated with decreased survival across all patients and subgroups, ALC was only significant in the general patient analysis. NLR's association with reduced OS was not statistically significant. These biomarkers may provide greater prognostic value in patients with oropharyngeal cancer and seemed to be more strongly associated with OS than DFS. Clinicaltrials.gov identifier: NCT00424255; URL: https://clinicaltrials.gov/ct2/show/study/NCT00424255.

The Association between Gut Microbiota and Serum Biomarkers in Children with Atopic Dermatitis.

Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives. We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3-12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman's correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions. It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system's response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families (Pasteurellaceae, Barnesiellaceae, Eubacteriaceae) was observed.

Experimental and Numerical Integrated Strategy for the Optimization of Microfluidic Parameters for Eudragit L100 Nanoparticles and Microparticles.

Oral immunization offers a minimally invasive administration, inducing local and systemic immune responses and facilitating mass immunization without needle-related risks. However, the gastrointestinal environment poses challenges, compromising vaccine effectiveness through enzymatic degradation and poor absorption by Peyer's patches. Advances in nanoparticle and microparticle (NP/MP) technology protect vaccines from degradation and enhance targeted release. The aim of this study was to develop pH-controlled polymeric carriers for the oral delivery of protein vaccines in order to target the antigen-presenting cells and M cells in the region of Peyer's patches. Here, myoglobin was chosen as a model protein vaccine. This study focuses on Eudragit L100, a pH-responsive polymer stable in acidic conditions and dissolving at higher pH, to develop carriers for controlled myoglobin release in the intestinal tract. A microfluidic-based manufacturing process for Eudragit L100 NPs and MPs is optimized using a comprehensive experimental and computational approach to obtain NPs and MPs through the same setup. Integrating in silico and experimental methods highlights the potential of numerical simulations to streamline final product development. This approach improves the efficiency and cost-effectiveness of NP/MP production, demonstrating how the combination of design of experiment and numerical simulations can optimize production parameters and refine manufacturing processes for advanced drug delivery systems.

Preparing the Laboratory for Neoadjuvant Cancer Immunotherapy: Insights from a Pathology Learning Collaborative

Abstract Introduction/Objective Neoadjuvant immunotherapy (NIT) is an emerging strategy to treat multiple types of early- stage resectable cancers by inducing a systemic anti-tumor immune response and increasing the likelihood of complete pathological response (pCR). The evaluation of pathological response following NIT is challenging and requires specific expertise. Traditional response criteria may be difficult to apply since immunotherapy may lead to unique changes in the tumor bed. Moreover, many laboratories may not feel prepared to evaluate pathologic response following immunotherapy given their lack of experience and the time required to accurately assess specimens and report findings. Methods/Case Report To explore ways to help laboratories prepare for these challenges, the American Society for Clinical Pathology (ASCP) formed an immuno-oncology learning collaborative to engage pathologists from different institutions and subspecialties. The group met over six months to review and discuss the implications of relevant literature, guideline recommendations, and emerging trends such as tumor-specific recommendations (eg, IASLC Neoadjuvant Therapy Pathologic Response Initiative) to pan-tumor immune-related pathologic response criteria (irPRC). ASCP then developed a series of educational resources based on recommendations made by the group. Results (if a Case Study enter NA) Members of the ASCP learning collaborative identified and prioritized several topics to help laboratories prepare and equip their teams to perform pathologic assessment after neoadjuvant immunotherapy in routine clinical practice. These included: definition and classification of pathological response criteria, assessing unique changes in the tumor bed (ie, regression bed), interpreting data from clinical trials, reporting results in routine clinical practice, organizing educational resources, and staffing workload. The group also emphasized the importance of collaborating with oncologists and surgeons and promoting communication about these topics within each institution. Conclusion Based on promising results from neoadjuvant immunotherapy clinical trials, we can expect more FDA approvals for neoadjuvant indications and a growing number of patients receiving this treatment. Pathologists and laboratory professionals need to prepare their institutions for a future where the assessment of pathological response in routine clinical practice will impact treatment decisions following surgical resection.

MXene-based nanozymes remodel tumor microenvironment for heterojunction-enhanced sonodynamic and chemodynamic therapy to boost robust cancer immunotherapy

Reactive oxygen species (ROS)-mediated sonodynamic therapy (SDT) holds increasing potential in treating deep-seated tumor owing to the high tissue-penetration depth, but hardly controls remote metastasis. To trigger robust cancer immunotherapy against malignant metastatic cancers, we report the rational construction of Z-scheme heterojunctions through decorating biocompatible Co3O4 nanoparticles with multiple enzyme-like catalytic activities onto Ti3C2Tx nanosheets to realize the augmented SDT and chemodynamic therapy (CDT). The deposition of Co3O4 nanoparticles not only sensitizes the sonodynamic activity of Ti3C2Tx nanosheets owing to the regulation of separation dynamics of electron-hole pairs, but also achieves the cascade amplification of ROS generation through Co2+-mediated Fenton-like reaction, Co3+-facilitated GSH depletion, and catalytic decomposition of endogenous H2O2 to relieve hypoxia. More importantly, the immunosuppressive TME could be reversed by the greatly enhanced ROS levels, ultimately inducing immunogenic cell death that promotes robust systemic immune responses. The heterojunction-enhanced SDT and CDT via Co3O4@Ti3C2Tx could trigger robust cancer immunotherapy, which achieves the eradication of primary tumors and suppression of distant tumors. This work highlights the potential of heterojunction engineering-enhanced SDT and CDT to trigger robust cancer immunotherapy.

Reshaping Immunosuppressive Tumor Microenvironment Using Ferroptosis/Cuproptosis Nanosensitizers for Enhanced Radioimmunotherapy

AbstractRadiotherapy, a traditional cancer treatment, not only controls local tumor growth but also potentially induces immunogenic cell death, initiating systemic immune responses. However, radiotherapy resistance and immunosuppressive tumor microenvironments often limit the potency of radiation‐induced anti‐tumor immune responses, rendering them insufficient for clinical applications. Consequently, trimetallic nanoparticles are constructed with dual enzymatic activity, AuBiCu‐distearoyl phosphoethanolamine‐PEG nanoparticles (AuBiCu‐PEG NPs), to synergistically improve radiotherapy resistance through X‐ray deposition, hypoxia alleviation, and ferroptosis and cuproptosis induction. This approach promotes radiotherapy‐induced immunogenic cell death and boosts anti‐tumor immune responses. Furthermore, AuBiCu‐PEG NPs effectively reversed radiation‐induced upregulation of programmed cell death 1 ligand 1 (PD‐L1), inhibit tumor immune evasion, and reshaped the immune microenvironment. Non‐invasive and real‐time longitudinal monitoring of nanoparticle accumulation in tumors can be achieved using spectral computed tomography (CT) and photoacoustic (PA) imaging. In summary, the designed AuBiCu‐PEG NPs serve as promising nanoplatforms for immune microenvironment remodeling and can be used in multimodal molecular imaging‐guided ferroptosis‐cuproptosis‐enhanced radiotherapy.

Effects of monoglyceride blend on systemic and intestinal immune responses, and gut health of weaned pigs experimentally infected with a pathogenic Escherichia coli

BackgroundMonoglycerides have emerged as a promising alternative to conventional practices due to their biological activities, including antimicrobial properties. However, few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance, immune response, and gut health using a disease challenge model. Therefore, this study aimed to investigate the effects of dietary monoglycerides of short- and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18.ResultsPigs supplemented with high-dose zinc oxide (ZNO) had greater (P < 0.05) growth performance than other treatments, but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period. Pigs in ZNO and antibiotic groups had lower (P < 0.05) severity of diarrhea than control, but the severity of diarrhea was not different between antibiotic and monoglycerides groups. Pigs fed with monoglycerides or ZNO had lower (P < 0.05) serum haptoglobin on d 2 or 5 post-inoculation than control. Pigs in ZNO had greater (P < 0.05) goblet cell numbers per villus, villus area and height, and villus height:crypt depth ratio (VH:CD) in duodenum on d 5 post-inoculation than pigs in other treatments. Pigs supplemented with monoglycerides, ZNO, or antibiotics had reduced (P < 0.05) ileal crypt depth compared with control on d 5 post-inoculation, contributing to the increase (P = 0.06) in VH:CD. Consistently, pigs in ZNO expressed the lowest (P < 0.05) TNFa, IL6, IL10, IL12, IL1A, IL1B, and PTGS2 in ileal mucosa on d 5 post-inoculation, and no difference was observed in the expression of those genes between ZNO and monoglycerides. Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control, particularly on carbohydrate and amino acid metabolism, while limited impacts on serum metabolites were observed in monoglycerides group when compared with control.ConclusionsThe results suggest that supplementation of monoglyceride blend may enhance disease resistance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation, although the effectiveness may not be comparable to high-dose zinc oxide.

Thermostatted Kinetic Theory Structures in Biophysics: Generalizations and Perspectives

The mathematical modeling of multicellular systems is an important branch of biophysics, which focuses on how the system properties emerge from the elementary interaction between the constituent elements. Recently, mathematical structures have been proposed within the thermostatted kinetic theory for the modeling of complex living systems and have been profitably employed for the modeling of various complex biological systems at the cellular scale. This paper deals with a class of generalized thermostatted kinetic theory frameworks that can stand in as background paradigms for the derivation of specific models in biophysics. Specifically, the fundamental homogeneous thermostatted kinetic theory structures of the recent literature are recovered and generalized in order to take into consideration further phenomena in biology. The generalizations concern the conservative, the nonconservative, and the mutative interactions between the inner system and the outer environment. In order to sustain the strength of the new structures, some specific models of the literature are reset into the style of the new frameworks of the thermostatted kinetic theory. The selected models deal with breast cancer, genetic mutations, immune system response, and skin fibrosis. Future research directions from the theoretical and modeling viewpoints are discussed in the whole paper and are mainly devoted to the well-posedness in the Hadamard sense of the related initial boundary value problems, to the spatial–velocity dynamics and to the derivation of macroscopic-scale dynamics.

A besyian regularisation neural network approach for hepatitis B virus spread prediction and immune system therapy model

The primary aim of the article is to analyze the response of the human immune system when it encounters the hepatitis B virus. This is done using a mathematical system of differential equations. The differential equation system has six components, likely representing various aspects of the immune response or virus dynamics. A Bayesian regularization neural network has been presented in the process of training. These networks are employed to find solutions for different categories or scenarios related to hepatitis B infection. The Adams method is used to generate reference data sets. The back-propagated artificial neural network, based on Bayesian regularization, is trained and validated using the generated data. The data is divided into three sets: 90% for training and 5% each for testing and validation. The correctness and effectiveness of the proposed neural network model have been assessed using various evaluation metrics. The metrics have been used in this study are Mean Square Error (MSE), histogram errors, and regression plots. These measures provide support to the neural network to approximate the immune response to the hepatitis B virus.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

We describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated positive correlation with interferon-related protein expression and negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insight into the lower airway and systemic proteome of severe pediatric vLRTI.

A New Frontier in Tumor Eradication: Harnessing In Vivo Cellular Reprogramming for Durable Cancer Immunotherapy.

Tumors evade immune detection by downregulating antigen presentation and hindering immune responses. Type 1 conventional dendritic cells (cDC1s) are vital in stimulating cytotoxic T cells against tumors. Ascic et al. are now demonstrating the in situ ability of PU.1, IRF8, and BATF3 (PIB) transcription factors to directly reprogram a plethora of tumors bypassing the suppressive effects of the tumor microenvironment, and leading to overall tumor regression while eliciting a systemic immune response that can protect from secondary tumor induction.

A broad appraisal of decompression-induced physiological stress in different simulated dive profiles

Background: The present study was designed to observe if different decompression profiles, calculated as a function of tissue supersaturation during ascent, would result in significantly different outcomes, measured through different physiological stress indicators, even in the absence of symptoms of decompression sickness. Aim: The aim of this study was to evaluate if simulated decompression profiles would affect the immune system, oxidative stress indicators, and heart rate variability. Methods: A total of 23 volunteers participated in two different experimental protocols in a dry hyperbaric chamber. These simulated dives comprised two different compression–decompression arrangements with the same maximum pressure and duration but different decompression profiles. Results: The shallow decompression profile with shorter deeper stops and longer shallow stops presented an increase in the standard deviation of the normal-to-normal R-R interval (a wide indicator of overall variability); the deep decompression profile with longer deeper stops and shorter shallow stops did not exhibit such increase. The shallow decompression profile resulted in an increase in neutrophil count and its microparticles (MPs), but no changes were observed for platelet count and its MPs, as well as for endothelial-derived MPs. In contrast, the deep decompression profile resulted in no changes in neutrophil count and its MPs, but a decrease in platelet count along with an increase in MPs from both platelets and endothelial cells. The observed difference might be related to different levels of decompression-related activation of immune system responses and oxidative processes triggered by different levels of inert gas supersaturation upon surfacing. Conclusion: From previous results and literature data, we present a tentative schematic of how the velocity of ascent would trigger (or not) pro-inflammatory and immune system responses that could ultimately lead to the development of decompression sickness. Relevance for patients: Increasing safety in exposure to hyperbaric environments and subsequent decompression by evaluating individual physiological responses to the process.

Exploring miRNA therapies and gut microbiome-enhanced CAR-T cells: advancing frontiers in glioblastoma stem cell targeting.

Glioblastoma multiforme (GBM) presents a formidable challenge in oncology due to its aggressive nature and resistance to conventional treatments. Recent advancements propose a novel therapeutic strategy combining microRNA-based therapies, chimeric antigen receptor-T (CAR-T) cells, and gut microbiome modulation to target GBM stem cells and transform cancer treatment. MicroRNA therapies show promise in regulating key signalling pathways implicated in GBM progression, offering the potential to disrupt GBM stem cell renewal. CAR-T cell therapy, initially successful in blood cancers, is being adapted to target GBM by genetically engineering T cells to recognise and eliminate GBM stem cell-specific antigens. Despite early successes, challenges like the immunosuppressive tumour microenvironment persist. Additionally, recent research has uncovered a link between the gut microbiome and GBM, suggesting that gut dysbiosis can influence systemic inflammation and immune responses. Novel strategies to modulate the gut microbiome are emerging, enhancing the efficacy of microRNA therapies and CAR-T cell treatments. This combined approach highlights the synergistic potential of these innovative therapies in GBM treatment, aiming to eradicate primary tumours and prevent recurrence, thereby improving patient prognosis and quality of life. Ongoing research and clinical trials are crucial to fully exploit this promising frontier in GBM therapy, offering hope to patients grappling with this devastating disease.

Evaluating the Therapeutic Efficacy of Lactobacillus Strains in the Management of Ulcerative Colitis: An Overview of Recent Advances.

Ulcerative Colitis (UC) known as a sub-category of Inflammatory Bowel Diseases (IBD) is a longterm condition that causes inflammation, irritation, and ulcers in the colon and rectum. Though the precise pathogenesis of UC is not fully understood yet, impaired immune responses and imbalanced intestinal microbiome composition have been regarded as two main key players in colitis pathobiology. As conventional treatments are challenged with limitations and side effects, finding a new therapeutic approach has gained increasing attention. Probiotic bacteria with multifunctional health-promoting properties have been considered novel therapeutic options. There is strong evidence indicating that probiotics exert their therapeutic effects mostly by regulating immune system responses and restoring gut microbiome homeostasis. These results validate the rationale behind the clinical application of probiotics in UC management whether prescribed alone or in combination with conventional therapy. This article explores the pathogenesis of UC, concentrating on the influence of immune dysregulation and intestinal microbiome imbalances. Also, it reviews recent in vitro, in vivo, and clinical studies that have demonstrated the efficacy of Lactobacillus species in decreasing UC symptoms by modifying immune responses, restoring gut microbiota balance, and promoting intestinal barrier function.

Breaking a dogma: orthodontic tooth movement alters systemic immunity

BackgroundThe prevailing paradigm posits orthodontic tooth movement (OTM) as primarily a localized inflammatory process. In this study, we endeavor to elucidate the potential ramifications of mechanical force on systemic immunity, employing a time-dependent approach.Materials and methodsA previously described mouse orthodontic model was used. Ni-Ti. springs were set to move the upper 1st-molar in C57BL/6 mice and the amount of OTM was. measured by µCT. Mice were allocated randomly into four experimental groups, each. corresponding to clinical phases of OTM, relative to force application. Terminal blood. samples were collected and a comprehensive blood count test for 7 cell types as well as. proteome profiling of 111 pivotal cytokines and chemokines were conducted. Two controls. groups were included: one comprised non-treated mice and the other mice with inactivated springs.ResultsSerum immuno-profiling unveiled alterations in cellular immunity, manifesting as. changes in percentages of leukocytes, monocytes, macrophages, neutrophils, and. lymphocytes, alongside key signaling factors in comparison to both control groups. The systemic cellular and molecular alterations triggered by OTM mirrored the dynamics previously described in the local immune response.ConclusionsAlthough the exact interplay between local and systemic immune responses to orthodontic forces require further elucidation, our findings demonstrate a tangible link between the two. Future investigations should aim to correlate these results with human subjects, and strive to delve deeper into the specific mechanisms by which mechanical force modulates the systemic immune response.