Immunological Pathways Research Articles

Immune biomarkers and secondary hemophagocytic lymphohistiocytosis: a scoping review protocol.

To identify immunological pathways and markers of severity of illness associated with clinical outcomes that may represent potential therapeutic targets in the management of secondary hemophagocytic lymphohistiocytosis. A broad range of immunomodulatory therapies is used to manage hemophagocytic lymphohistiocytosis, however the supporting evidence for these therapies is scarce. Identifying patients likely to experience more severe disease, or die, is currently extremely difficult, if not impossible. The identification of implicated cytokines in secondary disease can provide further support for the identification of high-risk patients and the development of targeted therapies. Studies reporting immune biomarker and cytokine measurement in adult patients (age >18 years) with secondary hemophagocytic lymphohistiocytosis. The proposed review will be conducted in line with the JBI methodology for scoping reviews. The MEDLINE (Ovid) and Embase (Ovid) databases will be searched, without date limitations. Data will be extracted using a data extraction tool developed by the reviewers. Relevant sources will be retrieved, and their citation details imported into the JBI System for the Unified Management, Assessment and Review of Information.

Potential Plasma Proteins (LGALS9, LAMP3, PRSS8 and AGRN) as Predictors of Hospitalisation Risk in COVID-19 Patients.

Background: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has posed unprecedented challenges to healthcare systems worldwide. Here, we have identified proteomic and genetic signatures for improved prognosis which is vital for COVID-19 research. Methods: We investigated the proteomic and genomic profile of COVID-19-positive patients (n = 400 for proteomics, n = 483 for genomics), focusing on differential regulation between hospitalised and non-hospitalised COVID-19 patients. Signatures had their predictive capabilities tested using independent machine learning models such as Support Vector Machine (SVM), Random Forest (RF) and Logistic Regression (LR). Results: This study has identified 224 differentially expressed proteins involved in various inflammatory and immunological pathways in hospitalised COVID-19 patients compared to non-hospitalised COVID-19 patients. LGALS9 (p-value < 0.001), LAMP3 (p-value < 0.001), PRSS8 (p-value < 0.001) and AGRN (p-value < 0.001) were identified as the most statistically significant proteins. Several hundred rsIDs were queried across the top 10 significant signatures, identifying three significant SNPs on the FSTL3 gene showing a correlation with hospitalisation status. Conclusions: Our study has not only identified key signatures of COVID-19 patients with worsened health but has also demonstrated their predictive capabilities as potential biomarkers, which suggests a staple role in the worsened health effects caused by COVID-19.

The gut microbiome and the brain.

The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions. The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function. Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions.

Topic modeling of neuropsychiatric diseases related to gut microbiota and gut brain axis using artificial intelligence based BERTopic model on PubMed abstracts

Gut microbiota play a crucial role in complex interactions of the gut brain axis between the gastrointestinal system and the central nervous system. The intricate network of bidirectional communication between the gut and brain, mediated through neural, hormonal, and immunological pathways, known as the gut-brain axis, has been implicated in the pathophysiology of several mental, neurological and behavioral disorders. Alterations in the gut microbiota composition, or dysbiosis, have been associated with disorders like Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Autism Spectrum Disorder, Ischemic Stroke, Eating Disorders, depression, anxiety, stress and addiction. In this study, a Python package BERTopic, based on Artificial Intelligence based Natural Language Processing using Transformer model BERT, specializing in topic modeling, was applied to abstracts of 3,482 PubMed articles published from year 2014 until May 2024, to explore the mental, neurological, and behavioral diseases influenced by the gut microbiota. There were some variations in individual runs of BERTopic due to stochastic nature of one of its components, but overall the discovered topics corresponded to major neuropsychiatric diseases. To understand the impact of the variability in outcomes ten repeated runs of BERTopic were performed with keeping identical parameters. The major topics that were found consistently in all the ten repeated runs of BERTopic were Depression, Alzheimer Disease, Autism Spectrum Disorder, Parkinson's Disease, Multiple Sclerosis, Ischemic Stroke, Anorexia Nervosa and Schizophrenia.

To Elucidate the Effective Role of Small Molecule Regulated lncRNAs in the Tumour Microenvironment in Immunotherapy.

The tumour microenvironment is a complex ecosystem comprising tumour cells, and cancer stem cells, and support cells that facilitate cancer growth and escape from treatment. Cancer immunotherapy focuses on immunological pathways such as PD-1/PD-L1 and CTLA-4 to target cancer stem cells via immune cells. Small molecules, immune checkpoint inhibitors, are employed to impede tumour growth by targeting cellular mediators in the cell cycle and tumour microenvironment. Long non-coding RNAs (lncRNAs) affect the growth, development, motility, and differentiation of cancer cells by regulating gene expression and are therefore considered important biomarkers. Small molecules demonstrate their effects on gene expression and behaviour of cancer cells by inducing lncRNAs. This relationship between lncRNAs and small molecules is of great importance in terms of their impact on cancer and the tumour microenvironment. The evaluation of this communication in clinical trials is of critical importance for the development of therapeutic strategies. This review provides a detailed description of the role of lncRNAs and small molecules in the tumour microenvironment and their relationship with cancer stem cells. Thus, the potential of controlling lncRNAs and using anti-cancer small molecules in TME to improve the efficacy of cancer therapy was evaluated.

Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches and Promising Horizons-A Comprehensive Review.

The research in neuroimmunomodulation aims to shed light on the complex relationships that exist between the immune and neurological systems and how they affect the human body. This multidisciplinary field focuses on the way immune responses are influenced by brain activity and how neural function is impacted by immunological signaling. This provides important insights into a range of medical disorders. Targeting both brain and immunological pathways, neuroimmunomodulatory approaches are used in clinical pain management to address chronic pain. Pharmacological therapies aim to modulate neuroimmune interactions and reduce inflammation. Furthermore, bioelectronic techniques like vagus nerve stimulation offer non-invasive control of these systems, while neuromodulation techniques like transcranial magnetic stimulation modify immunological and neuronal responses to reduce pain. Within the context of aging, neuroimmunomodulation analyzes the ways in which immunological and neurological alterations brought on by aging contribute to cognitive decline and neurodegenerative illnesses. Restoring neuroimmune homeostasis through strategies shows promise in reducing age-related cognitive decline. Research into mood disorders focuses on how immunological dysregulation relates to illnesses including anxiety and depression. Immune system fluctuations are increasingly recognized for their impact on brain function, leading to novel treatments that target these interactions. This review emphasizes how interdisciplinary cooperation and continuous research are necessary to better understand the complex relationship between the neurological and immune systems.

The implications of atorvastatin administration and the potential protective role of omega-3 on the submandibular salivary gland of albino rats (Histological, Histochemical, Ultrastructure, and Biochemical Study)

BackgroundHyperlipidemia is a risky condition that can lead to atherosclerosis and other cardiovascular problems. Statins are used to treat hyperlipidemia. The most recommended medicine to treat hyperlipidemia is atorvastatin. On the contrary, clinical trials validated statins' negative effects. Omega-3 fatty acids have antioxidant properties and have been shown to improve a variety of disease processes in the general population, including inflammatory and immunological pathways, various cardiovascular diseases, and lipid regulation. The present research aimed to determine how atorvastatin affected the submandibular salivary gland (SMG) and whether omega-3 may have a protective impact. MethodsThirty adult male albino rats were divided into three equal groups and received drugs orally as a single daily dose for one week. Control group (I): received normal saline. Atorvastatin group (II): received a dose of 80 mg Kg-1 of Atorvastatin. Group III: received Omega-3 before Atorvastatin. All rats were sacrificed 2 h following the last dose, and blood samples were gathered for the biochemical study of fasting blood glucose level (FBGL). Specimens were obtained and processed for histological and histochemical studies. ResultsAtorvastatin-treated rats showed degeneration of SMG acini. The acinar cells showed cytoplasmic vacuoles with dilated RER. Histochemical results revealed a marked decrease in total proteins. The biochemical study revealed an elevation in FBGL. The administration of Omega-3 with Atorvastatin minimizes these changes. ConclusionAtorvastatin has been proven to induce histological changes in SMG, and these changes can be attenuated by Omega-3. However, Omega-3 has no effect on FBGL.

Bugs and Brains: The Microbiome &amp; Dementia

Interest in the microbiome and its correlation with different neurological diseases has grown significantly over the past decade. The gut microbiome contains a vast array of diverse organisms living in the gastrointestinal (GI) tract. Predominantly composed of bacteria, the gut microbiome helps regulate homeostasis and metabolism in the host, aiding in immune system development as well as vitamin and nutrient absorption. Studies suggest that, in addition to providing humans with these physiological benefits, the gut microbiome is also linked to and communicates with the brain via the gut-brain axis (GBA). Long-standing research on the GBA has demonstrated that the GI tract and the central nervous system are interconnected through both neurological and immunological signaling pathways. Recent research is expanding our understanding of the microbiome and the GBA, revealing correlations between the microbiome impact on the GBA and neurological conditions such as Alzheimer’s dementia and Lewy body dementia, going as far as to identify and highlight specific microbial species that may serve as risk or protective factors for various forms of dementia. This letter aims to highlight the current findings and recommend the use of tools such as microbial cell-free DNA testing to gain a better understanding of the role of gut dysbiosis in dementia patients.

Analyzing Porcine Corneal Xenograft Compatibility: In Silico Insights on Graft Outcomes

Background: Corneal transplantation faces significant challenges due to the shortage in donor corneas. Porcine corneas have emerged as a potential solution due to their similarities in biomechanical properties with pigs, yet xenoimmune rejection poses an obstacle to their efficacy. Methods: In this study, in silico methods were employed to analyze the compatibility of porcine corneal xenografts, focusing on two key aspects: the comparison of corneal matrix proteins and investigation of the immunological mediators and pathways involved in corneal graft rejection. The amino acid sequences of the fourteen (14) most abundant proteins in the corneal matrix were compared to determine their structural and functional differences. The primary amino acid structures and compositions, theoretical pI, and grand average of hydropathicity were determined and compared between the two species. Results: In graft performance, similarities and differences between the donor and recipient tissues influence the success of transplantation. When the proteins closely resemble each other, in terms of structural characteristics and biochemical properties, the host’s immune system is less likely to recognize the tissue as foreign. The immunological mediators and pathways involved in corneal graft rejection were investigated, elucidating the mechanisms underlying xenograft incompatibility. Based on the results generated from STRING, the specific groups of molecules that are involved in the immune-mediated rejection process are costimulatory molecules, cytokines, immune checkpoint molecules, apoptosis regulators, cell adhesion molecules, growth factors, neuropeptides and hormones, certain receptors, the cytotoxic molecule GZMA, and the chemokine CCL5. Conclusions: The results of this study establish that the porcine cornea has a high suitability for corneal xenotransplantation into humans but requires immune-based therapeutic interventions to increase graft acceptance.

Comprehensive insight into 3D bioprinting technology for brain tumor modeling

Glioblastoma is one of the most common primary malignant brain tumors with a poor prognosis and high mortality rate. Because only small lipophilic molecules can penetrate the blood-brain barrier, chemotherapy and immunotherapy are limited in their ability to effectively treat brain tumor. Three-dimensional (3D) bioprinting has the potential to model the 3D environment of human pathology and diseases directly. In many cancers, 3D bioprinting technology closely mimics the tumor microenvironment, making it a promising tool for drug screening and uncovering the mechanisms of cancer initiation and progression. Recent 3D bioprinting technologies have been developed to recreate the dynamic interactions between the tumor and endothelial cells. Brain tumor models using 3D bioprinting technology can reconstruct the biophysical heterogeneity and immune interactions in the brain. These advanced models regulate the organization of tumor structures for preclinical drug testing and reveal the immunological pathways involved in brain tumor. Here, we highlight 3D bioprinting technologies that can replace conventional in vitro models for brain tumor treatment.

Assessment of Corneal Graft Outcomes in a Murine Model of Endothelial Keratoplasty.

Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) as donors and BALB/c mice as recipients. Slit-lamp examination and optical coherence tomography were performed for clinical evaluations for 16 weeks post-procedure. Criteria for the assessment of corneal opacity were established and the animals were graded weekly. Additionally, we assessed corneal endothelial cell density by harvesting the corneas and staining with zonula occludens-1 (ZO-1). Lastly, lymph nodes were collected, and CD4+ T cells were MACS-sorted and co-cultured with syngeneic or allogeneic antigen-presenting cells (APCs) to assess the IFN-γ expression levels by alloreactive Th1 cells (ELISPOT) in response to the direct (donor) or indirect (host) pathways of sensitization. Results: We observed graft failure in four animals, including irreversible corneal opacity, graft detachment, and anterior synechiae in the first four weeks. The remaining animals were graded between 0 and 5 as per the established criteria. The total and graft corneal thickness and endothelial cell density progressively worsened with a higher grade of corneal opacity. The direct allosensitization of Th1 cells was significantly higher in mice with a higher grade of corneal opacity. At 16 weeks follow-up, the grafts remained stable with low opacity scores in syngeneic EK recipients; however, the opacity scores were higher and variable in allogeneic EK recipients. Conclusions: These findings establish a standardized protocol to assess the graft outcomes in a murine model of EK. Furthermore, we delineate the underlying immunological pathway that contributes to the immune-mediated rejection of grafts in this model.

Establishment and characterization of a gill cell line from Takifugu obscurus and transcriptome analysis of its gene expression profiles upon low temperature

Takifugu obscurus is a farmed fish of great economic importance in China. The rapid development of T. obscurus aquaculture industry has been accompanied by disease and low-temperature stress, resulting in huge economic losses. Cell lines are used extensively in teleost physiology and pathology as the most cost-effective platform for in vitro research. A novel gill cell line of T. obscurus (named TOG) was first successfully established, and passed through 52 generations. The optimal conditions for TOG growth were 20 % FBS concentration and 24 °C, TOG could be grown in both hypotonic (150 mOsmol-kg-1) and hypertonic (600 mOsmol-kg-1) environments. TOG was determined to be derived from T. obscurus by sequencing the mitochondrial COI gene. Karyotype analysis revealed that the chromosome number of TOG was 44 (2n = 44). Transfection experiment showed that TOG was able to express foreign genes. Furthermore, several immune-related genes were significantly up-regulated in TOG after LPS and poly (I:C) stimulation, including tlr3, isg15, il1β and il10. Additionally, transcriptome analysis of TOG under low-temperature stress (24 °C, 18 °C, 12 °C, 10 °C and 8 °C) found that differentially expressed genes (DEGs) were significantly clustered in several immunological and energy metabolic pathways, and cold stress could disrupt the immune barrier and reduce immunity by downregulating the immune-related pathways. Additionally, weighted gene co-expression network analysis (WGCNA) revealed that bule module and turquoise module, which were closely correlated with low temperature and the degree of fish damage, were both predominantly found in PPAR, NOD-like receptor and Toll-like receptor signaling pathway. Hub genes were identified in these two modules, including mre11, clpb, dhx15, ddx18 and utp15. TOG cell line will become an effective experimental platform for genetic and immunological research, and our results would help us gain a deeper insight into the molecular mechanism of cold tolerance in teleost.

Investigation of the anti-skin aging effects of taurine through mendelian randomization analysis of its relationship with immune cells.

Aging skin, exacerbated by external factors like UV radiation and pollutants, is a major cosmetic concern. Taurine, renowned for its antioxidant and anti-inflammatory properties, may combat skin aging. We performed mendelian randomization (MR) analysis to investigate the causal link between taurine and immune cells linked to skin aging. To investigate the association between taurine and immune cells using mendelian randomization, to thereby explore the mechanism through which taurine exerts anti-aging effects on the skin via immune modulation. A MR approach was employed using taurine-level data from the Ieu Open GWAS Project and immunocyte traits from a large European cohort. MR-Egger regression, weighted median estimation, and inverse variance weighting all provided statistical insights into causality. Sensitivity analyses assessed the heterogeneity and pleiotropy among the genetic instruments used. MR analysis identified a causal relationship between taurine levels and 10 immunocyte phenotypes, with taurine found to be negatively and positively associated with three and seven phenotypes, respectively. Sensitivity analysis revealed no significant heterogeneity or pleiotropy, suggesting reliable MR findings. This study provides insights into the immunological pathways by which taurine contributes to skin anti-aging effects, suggesting that increasing taurine levels could offer a novel strategy for anti-aging skincare.

Biomarkers in cardiorenal syndrome, a potential use in precision medicine.

Cardiorenal syndrome refers to the interrelated dysfunction of the heart or kidney resulting in a cascade of feedback mechanisms, hemodynamic, neurohormonal, and immunological and/or biochemical feedback pathways causing damage in the other organ. Cardiorenal syndrome is categorized into five clinical subtypes depending on the perceived primary precipitant of organ injury and is associated with high morbidity and mortality. Therefore, the development of tools for the earliest identification of cardiorenal syndrome in hospitalized patients is of extremely high significance to ameliorate the prognosis and outcome of these patients. There is increasing interest in identifying molecules serving as biomarkers, reflecting hemodynamic changes, heart and kidney damage and/or dysfunction and oxidative stress-induced cell damage or changes in the extracellular matrix of both the heart and kidneys. Biomarkers provide important insights into the pathophysiology of cardiorenal syndrome and are invaluable tools to predict the decrease in renal function during cardiac dysfunction and vice versa. Based on the pathophysiological mechanisms of cardiorenal syndrome, we reviewed and evaluated the available literature on serum and urinary biomarkers as predictors of kidney and/or heart injury. In addition, heart- and kidney-specific biomarkers were also evaluated based ontheir reference to kidney and cardiac (dys)function respectively, and whether they would provide any prediction and prognostication of cardiorenal syndrome. In this article, we discuss the current knowledge on the pathophysiology of different types ofcardiorenal syndrome, examine the clinical utility of candidate biomarkers in the early diagnosis of cardiorenalsyndrome, and guide treatment by evaluating the respective roles of the involved pathophysiological pathways.

Immune-based Machine learning Prediction of Diagnosis and Illness State in Schizophrenia and Bipolar Disorder

BackgroundSchizophrenia and bipolar disorder frequently face significant delay in diagnosis, leading to being missed or misdiagnosed in early stages. Both disorders have also been associated with trait and state immune abnormalities. Recent machine learning-based studies have shown encouraging results using diagnostic biomarkers in predictive models, but few have focused on immune-based markers. Our main objective was to develop supervised machine learning models to predict diagnosis and illness state in schizophrenia and bipolar disorder using only a panel of peripheral kynurenine metabolites and cytokines. MethodsThe cross-sectional I-GIVE cohort included hospitalized acute bipolar patients (n = 205), stable bipolar outpatients (n = 116), hospitalized acute schizophrenia patients (n = 111), stable schizophrenia outpatients (n = 75) and healthy controls (n = 185). Serum kynurenine metabolites, namely tryptophan (TRP), kynurenine (KYN), kynurenic acid (KA), quinaldic acid (QUINA), xanthurenic acid (XA), quinolinic acid (QUINO) and picolinic acid (PICO) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), while V-plex Human Cytokine Assays were used to measure cytokines (interleukin-6 (IL-6), IL-8, IL-17, IL-12/IL23-P40, tumor necrosis factor-alpha (TNF-ɑ), interferon-gamma (IFN-γ)). Supervised machine learning models were performed using JMP Pro 17.0.0. We compared a primary analysis using nested cross-validation to a split set as sensitivity analysis. Post-hoc, we re-ran the models using only the significant features to obtain the key markers. ResultsThe models yielded a good Area Under the Curve (AUC) (0.804, Positive Prediction Value (PPV) = 86.95; Negative Prediction Value (NPV) = 54.61) for distinguishing all patients from controls. This implies that a positive test is highly accurate in identifying the patients, but a negative test is inconclusive. Both schizophrenia patients and bipolar patients could each be separated from controls with a good accuracy (SCZ AUC 0.824; BD AUC 0.802). Overall, increased levels of IL-6, TNF-ɑ and PICO and decreased levels of IFN-γ and QUINO were predictive for an individual being classified as a patient. Classification of acute versus stable patients reached a fair AUC of 0.713. The differentiation between schizophrenia and bipolar disorder yielded a poor AUC of 0.627. ConclusionsThis study highlights the potential of using immune-based measures to build predictive classification models in schizophrenia and bipolar disorder, with IL-6, TNF-ɑ, IFN-γ, QUINO and PICO as key candidates. While machine learning models successfully distinguished schizophrenia and bipolar disorder from controls, the challenges in differentiating schizophrenic from bipolar patients likely reflect shared immunological pathways by the both disorders and confounding by a larger state-specific effect. Larger multi-centric studies and multi-domain models are needed to enhance reliability and translation into clinic.

Types of cell death and their relations to host immunological pathways.

Various immune pathways have been identified in the host, including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. While TH2 and TH9 responses primarily target multicellular parasites, host immune pathways directed against viruses, intracellular microorganisms (such as bacteria, protozoa, and fungi), and extracellular microorganisms can employ programmed cell death mechanisms to initiate immune responses or execute effective strategies for pathogen elimination. The types of programmed cell death involved include apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, and NETosis. Specifically, apoptosis is associated with host anti-virus eradicable THαβ immunity, autophagy with host anti-virus tolerable TH3 immunity, pyroptosis with host anti-intracellular microorganism eradicable TH1 immunity, ferroptosis with host anti-intracellular microorganism tolerable TH1-like immunity, necroptosis with host anti-extracellular microorganism eradicable TH22 immunity, and NETosis with host anti-extracellular microorganism tolerable TH17 immunity.

Serum biomarkers at disease onset for personalized therapy in multiple sclerosis.

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

Tuberculosis-related Mood Disorders: Probiotics as a Next-Generation Strategy

Introduction: Tuberculosis-related mood disorders are well-known but least researched. As frequent comorbidity of tuberculosis (TB), depression is linked to poor adherence to treatment for a number of illnesses. The exact causal mechanism and pathways behind TB disease and associated mental illnesses are unclear. The disease's severity and duration impact the occurrence of depression, and MDR-TB enhances this risk. To summarise the information on the association between depression and unfavourable outcomes of TB treatment, we carried out a narrative review. Objective: The objective of this study is to provide an overview of probiotics as a cutting-edge treatment for mood disorders linked to tuberculosis. Methods: A systematic stepwise online database research was done for systematic reviews, original studies, and review papers published on probiotics and mental disorders associated with tuberculosis in PubMed/MEDLINE, Google Scholar, and Web of Science. The reference lists for these articles were also used as sources for the bibliography Results: The gut microbiota and the brain are connected by neuroendocrine-immune pathways. The diversity and abundance of microbiota Proteobacteria, Actinobacteria Bacteroides, and Firmicutes are reduced in tuberculosis patients. Through the stimulation of different immunological responses or visceral sensory pathways, these changes in the gut microbiome may be a contributing factor in emotional instability and mood disorders. Probiotics also lessen the stress response caused by cortisol, in addition to releasing neurotransmitters, including GABA, serotonin, noradrenaline, acetylcholine, and dopamine, in various brain regions. Probiotics are the most prevalent in the sensory brain network of the brain, which controls the brain's core processing of emotions and sensations. In addition, they produce short-chain fatty acids (SCAFs) from the bacterial fermentation of fibre in the colon, such as butyrate, which inhibits histone deacetylase, binds to G protein-coupled receptors, and serves as an energy metabolite. Butyrate plays a significant role in maintaining brain health by having antimanic and antidepressant effects. Several clinical research on patients with MDD has revealed that probiotics have favourable effects on depressive symptoms. Conclusion: The central dopamine system, inflammation, the BDNF system, and the gut-brain axis are all recognised to play crucial roles in the pathogenesis of MDD. Commercial probiotics that generate butyrate-producing SCFAs and those resistant to metabolic disorders (such as Bacteroidetes) may be beneficial for tuberculosis-related MDD during and after treatment. In this situation, using bacteria that produce SCFA could be a cutting-edge method of treating clinical MDD.

Ferritin Heavy-like subunit is involved in the innate immune defense of the red swamp crayfish Procambarus clarkii.

Iron-binding proteins, known as ferritins, play pivotal roles in immunological response, detoxification, and iron storage. Despite their significance to organisms, little is known about how they affect the immunological system of the red swamp crayfish (Procambarus clarkii). In our previous research, one ferritin subunit was completely discovered as an H-like subunit (PcFeH) from P. clarkii. The full-length cDNA of PcFerH is 1779 bp, including a 5'-UTR (untranslated region, UTR) of 89 bp, 3'-UTR (untranslated region, UTR) of 1180 bp and an ORF (open reading frame, ORF) of 510 bp encoding a polypeptide of 169 amino acids that contains a signal peptide and a Ferritin domain. The deduced PcFerH protein sequence has highly identity with other crayfish. PcFerH protein's estimated tertiary structure is quite comparable to animal structure. The PcFerH is close to Cherax quadricarinatus, according to phylogenetic analysis. All the organs examined showed widespread expression of PcFerH mRNA, with the ovary exhibiting the highest levels of expression. Additionally, in crayfish muscles, intestines, and gills, the mRNA transcript of PcFerH was noticeably up-regulated, after LPS and Poly I:C challenge. The expression of downstream genes in the immunological signaling system was suppressed when the PcFerH gene was knocked down. All of these findings suggested that PcFerH played a vital role in regulating the expression of downstream effectors in the immunological signaling pathway of crayfish.

Early human migration determines the risk of being attacked by wolves: ethnic gene diversity on the development of systemic lupus erythematosus.

The prevalence of systemic lupus erythematosus (SLE) varies significantly based on ethnicity rather than geographic distribution; thus, the prevalence is higher in Asian, Hispanic, and Black African populations than in European populations. The risk of developing lupus nephritis (LN) is the highest among Asian populations. Therefore, we hypothesize that human genetic diversity between races has occurred through the early human migration and human genetic adaptation to various environments, with a particular focus on pathogens. Additionally, we compile the currently available evidence on the ethnic gene diversity of SLE and how it relates to disease severity. The human leukocyte antigen (HLA) locus is well established as associated with susceptibility to SLE; specific allele distributions have been observed across diverse populations. Notably, specific amino acid residues within these HLA loci demonstrate significant associations with SLE risk. The non-HLA genetic loci associated with SLE risk also varies across diverse ancestries, implicating distinct immunological pathways, such as the type-I interferon and janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways in Asians, the type-II interferon signaling pathway in Europeans, and B cell activation pathway in Africans. Furthermore, assessing individual genetic susceptibility using genetic risk scores (GRS) for SLE helps to reveal the diverse prevalence, age of onset, and clinical phenotypes across different ethnicities. A higher GRS increases the risk of LN and the severity of SLE. Therefore, understanding ethnic gene diversity is crucial for elucidating disease mechanisms and SLE severity, which could enable the development of novel drugs specific to each race.