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TANK-binding kinase 1 (TBK1) is a member of the IKK family and plays a crucial role in the activation of non-canonical NF-kB signaling and type I interferon responses. The aberrant activation of TBK1 contributes to the proliferation and survival of various types of tumor cells, particularly in specific mutational or tumorous contexts. Inhibitors targeting TBK1 are under development and application in both in vivo and in vitro settings, yet their clinical efficacy remains limited. Numerous literatures have shown that TBK1 can exhibit both tumor promoting and tumor inhibiting effects. TBK1 acts as a pivotal node within the innate immune pathway, mediating anti-tumor immunity through the activation of innate immune responses. Facilitating interferon-I (IFN-I) production represents a critical mechanism through which TBK1 bridges these processes. IFN has been shown to exert both beneficial and detrimental effects on tumor progression. Hence, the paradoxical role of TBK1 in tumor development may necessitate acknowledgment in light of its downstream IFNI signaling cascade. In this paper, we review the signaling pathways mediated by TBK1 in various tumor contexts and summarize the dual roles of TBK1 and the TBK1-IFN pathways in both promoting and inhibiting tumor progression. Additionally, we highlight the significance of the TBK1-IFN pathway in clinical therapy, particularly in the context of immune response. We anticipate further advancements in the development of TBK1 inhibitors as part of novel cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host's immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host's innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials. [ABSTRACT FROM AUTHOR]

Innate lymphoid cells type 3 (ILC3s) are the first line sentinels at the mucous tissues, where they contribute to the homeostatic immune response in a major way. Also, they have been increasingly appreciated as important modulators of chronic inflammatory and autoimmune responses, both locally and systemically. The proper identification of ILC3 is of utmost importance for meaningful studies on their role in immunity. Flow cytometry is the method of choice for the detection and characterization of ILC3. However, the analysis of ILC3-related papers shows inconsistency in ILC3 phenotypic definition, as different inclusion and exclusion markers are used for their identification. Here, we present these discrepancies in the phenotypic characterization of human and mouse ILC3s. We discuss the pros and cons of using various markers for ILC3 identification. Furthermore, we consider the possibilities for the efficient isolation and propagation of ILC3 from different organs and tissues for in-vitro and in-vivo studies. This paper calls upon uniformity in ILC3 definition, isolation, and propagation for the increased possibility of confluent interpretation of ILC3's role in immunity. [ABSTRACT FROM AUTHOR]

Despite innovations in cancer therapeutics, cancer remains associated with high mortality and is one of biggest health challenges worldwide. Therefore, developing precise cancer imaging and effective treatments is an unmet clinical need. A relatively novel type of therapeutics are heavy chain variable domain antibody fragments (VHHs) derived from llamas. Here, we explored the suitability of VHHs for cancer imaging and therapy through reviewing the existing literature. We searched the MEDLINE, EMBASE and Cochrane databases and identified 32 papers on molecular imaging and 41 papers on therapy that were suitable for comprehensive reviewing. We found that VHHs harbor a higher specificity and affinity compared to mAbs, which contributes to high-quality imaging and less side-effects on healthy cells. The employment of VHHs in cancer imaging showed remarkably shorter times between administration and imaging. Studies showed that 18F and 99mTc are two optimal radionuclides for imaging with VHHs and that site-specific labelling is the optimal conjugation modality for VHHs with radionuclide or fluorescent molecules. We found different solutions for reducing kidney retention and immunogenicity of VHHs. VHHs as anticancer therapeutics have been tested in photodynamic therapy, targeted radionuclide therapy, immunotherapy and molecular targeted therapy. These studies showed that VHHs target unique antigen epitopes, which are distinct from the ones recognized by mAbs. This advantage means that VHHs may be more effective for targeted anticancer therapy and can be combined with mAbs. We found that high cellular internalization and specificity of VHHs contributes to the effectiveness and safety of VHHs as anticancer therapeutics. Two clinical trials have confirmed that VHHs are effective and safe for cancer imaging and therapy. Together, VHHs seem to harbor several advantages compared to mAbs and show potential for application in personalized treatment for cancer patients. VHH-based imaging and therapy are promising options for improving outcomes of cancer patients. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, a key target for regulating the tumor immune microenvironment, is important in cancer treatment and progression. TREM2 is an immune signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor immune responses by inhibiting T cell-mediated immune responses, but it also influences tumorigenesis by affecting NK cell-mediated antitumor immunity. Noticeably, TREM2 expression levels also vary significantly among different tumor cells, and it can regulate tumor progression by modulating various signaling pathways. Above all, by summarizing the role of TREM2 in cancer immunotherapy and the mechanism by which TREM2 regulates tumor progression, this paper clarifies TREM2's role in both tumor progression and cancer therapy, identifying a new therapeutic target for oncology diseases. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is characterized by a rapid decline in renal function and is associated with a high morbidity and mortality rate. At present, the underlying mechanisms of AKI remain incompletely understood. Immune disorder is a prominent feature of AKI, and dendritic cells (DCs) play a pivotal role in orchestrating both innate and adaptive immune responses, including the induction of protective proinflammatory and tolerogenic immune reactions. Emerging evidence suggests that DCs play a critical role in the initiation and development of AKI. This paper aimed to conduct a comprehensive review and analysis of the role of DCs in the progression of AKI and elucidate the underlying molecular mechanism. The ultimate objective was to offer valuable insights and guidance for the treatment of AKI. [ABSTRACT FROM AUTHOR]

As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a widespread but still underdiagnosed parasitic disease that affects both humans and animals. There are at least 20 pathogenic species of Leishmania, most of them being zoonotic. The diagnosis of leishmaniasis remains a major challenge, with an important role being played by the species of parasites involved, the genetic background, the immunocompetence of the host. This paper brings to the fore the sensitivity of the balance in canine and human leishmaniasis and addresses the importance of the host's immune response in establishing a correct diagnosis, especially in certain cases of asymptomatic leishmaniasis, or in the situation the host is immunosuppressed or acquired leishmaniasis through vertical transmission. The methods considered as a reference in the diagnosis of leishmaniasis no longer present certainty, the diagnosis being influenced mostly by the immune response of the host, which differs according to the presence of other associated diseases or even according to the breed in dogs. Consequently, the diagnosis and surveillance of leishmaniasis cases remains an open topic, requiring new diagnostic methods adapted to the immunological state of the host. [ABSTRACT FROM AUTHOR]

Immunotherapy is a therapeutic approach that employs immunological principles and techniques to enhance and amplify the body's immune response, thereby eradicating tumor cells. Immunotherapy has demonstrated effective antitumor effects on a variety of malignant tumors. However, when applied to humans, many immunotherapy drugs fail to target lesions with precision, leading to an array of adverse immune-related reactions that profoundly limit the clinical application of immunotherapy. Nanodrug delivery systems enable the precise delivery of immunotherapeutic drugs to targeted tissues or specific immune cells, enhancing the immune antitumor effect while reducing the number of adverse reactions. A nanodrug delivery system provides a feasible strategy for activating the antitumor immune response by the following mechanisms: 1) increased targeting and uptake of vaccines by DCs, which enhances the efficacy of the immune response; 2) increased tumor cell immunogenicity; 3) regulation of TAMs and other cells by, for example, regulating the polarization of TAMs and interfering with TAN formation, and ECM remodeling by CAFs; and 4) interference with tumor immune escape signaling pathways, namely, the PD-1/PD-L1, FGL1/LAG-3 and IDO signaling pathways. This paper reviews the progress of nanodrug delivery system research with respect to tumor immunotherapy based on tumor immunomodulation over the last few years, discussing the promising future of these delivery systems under this domain. [ABSTRACT FROM AUTHOR]

A high tumor mutation burden (TMB) is known to drive the response to immune checkpoint inhibitors (ICI) and is associated with favorable prognoses. However, because it is a one-dimensional numerical representation of non-synonymous genetic alterations, TMB suffers from clinical challenges due to its equal quantification. Since not all mutations elicit the same antitumor rejection, the effect on immunity of neoantigens encoded by different types or locations of somatic mutations may vary. In addition, other typical genomic features, including complex structural variants, are not captured by the conventional TMB metric. Given the diversity of cancer subtypes and the complexity of treatment regimens, this paper proposes that tumor mutations capable of causing various degrees of immunogenicity should be calculated separately. TMB should therefore, be segmented into more exact, higher dimensional feature vectors to exhaustively measure the foreignness of tumors. We systematically reviewed patients’ multifaceted efficacy based on a refined TMB metric, investigated the association between multidimensional mutations and integrative immunotherapy outcomes, and developed a convergent categorical decision-making framework, TMBserval (Statistical Explainable machine learning with Regression-based VALidation). TMBserval integrates a multiple-instance learning concept with statistics to create a statistically interpretable model that addresses the broad interdependencies between multidimensional mutation burdens and decision endpoints. TMBserval is a pan-cancer-oriented many-to-many nonlinear regression model with discrimination and calibration power. Simulations and experimental analyses using data from 137 actual patients both demonstrated that our method could discriminate between patient groups in a high-dimensional feature space, thereby rationally expanding the beneficiary population of immunotherapy. [ABSTRACT FROM AUTHOR]

Cell-based mathematical models have previously been developed to simulate the immune system in response to pathogens. Mathematical modeling papers which study the human immune response to pathogens have predicted concentrations of a variety of cells, including activated and resting macrophages, plasma cells, and antibodies. This study aims to create a comprehensive mathematical model that can predict cytokine levels in response to a gram-positive bacterium, S. aureus by coupling previous models. To accomplish this, the cytokines Tumor Necrosis Factor Alpha (TNF- α), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and Interleukin 10 (IL-10) are included to quantify the relationship between cytokine release from macrophages and the concentration of the pathogen, S. aureus, ex vivo. Partial differential equations (PDEs) are used to model cellular response and ordinary differential equations (ODEs) are used to model cytokine response, and interactions between both components produce a more robust and more complete systems-level understanding of immune activation. In the coupled cellular and cytokine model outlined in this paper, a low concentration of S. aureus is used to stimulate the measured cellular response and cytokine expression. Results show that our cellular activation and cytokine expression model characterizing septic conditions can predict ex vivo mechanisms in response to gram-negative and gram-positive bacteria. Our simulations provide new insights into how the human immune system responds to infections from different pathogens. Novel applications of these insights help in the development of more powerful tools and protocols in infection biology. [ABSTRACT FROM AUTHOR]

Ferroptosis is a non-apoptotic regulatory form of cell death that has sparked significant interest and research in cancer treatment and certain small chemical inducers have been used in the clinic. These inducers’s weak water solubility, poor targeting, rapid metabolism; and other undesirable characteristics; however, for therapeutic approaches that combine immunotherapy and ferroptosis, challenges such as medication delivery, the complexity of the tumor microenvironment, and immunosuppression remain. The targeted, low toxicity, and efficient distribution benefits of nanotechnology have considerably enhanced the therapeutic efficacy of combining immunotherapy with ferroptosis. This paper describes the distinct mechanism of ferroptosis in tumor therapy and immunotherapy, as well as the application and benefits of nanotechnology in the combination of tumor immunotherapy and ferroptosis. [ABSTRACT FROM AUTHOR]

Primary liver cancer is one of the most common malignant tumors in China. The vast majority of primary liver cancer are hepatocellular carcinoma. Due to its high incidence and mortality from HCC, HCC has always been a feared type of cancer. Liver transplantation, as one of the important means to treat advanced liver cancer, has brought new hope to patients. However, as patients have been in a state of immunosuppression after liver transplantation, these patients face new problems of HCC recurrence and metastasis. A increasing number of studies have proved that blocking the PD-1/PD-L1 signaling pathway and restoring the immune killing inhibition of T cells can produce better therapeutic effects on tumors and chronic infectious diseases. As a promising treatment in the field of tumor immunotherapy, PD-1/PD-L1 inhibitors have achieved important results in liver cancer patients, but their application in liver transplantation patients is still highly controversial. This paper will introduce the mechanism of action of PD-1/ PD-L1 signaling pathway and the current basic and clinical studies of PD-1/PD-L1 signaling pathway associated with immune response in HCC transplantation. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), a disease caused by bacteria Mycobacterium tuberculosis (Mtb), remains one of the major infectious diseases of humans with 10 million TB cases and 1.5 million deaths due to TB worldwide yearly. Upon exposure of a new host to Mtb, bacteria typically infect one local site in the lung, but over time, Mtb disseminates in the lung and in some cases to extrapulmonary sites. The contribution of various host components such as immune cells to Mtb dynamics in the lung, its dissemination in the lung and outside of the lung, remains incompletely understood. Here we overview different types of mathematical models used to gain insights in within-host dynamics of Mtb; these include models based on ordinary or partial differential equations (ODEs and PDEs), stochastic simulation models based on ODEs, agent-based models (ABMs), and hybrid models (ODE-based models linked to ABMs). We illustrate results from several of such models and identify areas for future resesarch. [ABSTRACT FROM AUTHOR]

ADAM17 is a member of the a disintegrin and metalloproteinase (ADAM) family of transmembrane proteases involved in the shedding of some cell membrane proteins and regulating various signaling pathways. More than 90 substrates are regulated by ADAM17, some of which are closely relevant to tumor formation and development. Besides, ADAM17 is also responsible for immune regulation and its substrate-mediated signal transduction. Recently, ADAM17 has been considered as a major target for the treatment of tumors and yet its immunomodulatory roles and mechanisms remain unclear. In this paper, we summarized the recent understanding of structure and several regulatory roles of ADAM17. Importantly, we highlighted the immunomodulatory roles of ADAM17 in tumor development, as well as small molecule inhibitors and monoclonal antibodies targeting ADAM17. [ABSTRACT FROM AUTHOR]

Cuproptosis is a newly discovered new mechanism of programmed cell death, and its unique pathway to regulate cell death is thought to have a unique role in understanding cancer progression and guiding cancer therapy. However, this regulation has not been studied in low grade glioma (LGG) at present. In this study, data on low grade glioma patients were downloaded from the TCGA database. We screened the genes related to cuproptosis from the published papers and confirmed the lncRNAs related to them. We applied univariate/ multivariate, and LASSO regression algorithms, finally identified 11 lncRNAs for constructing prognosis prediction models, and constructed a risk scoring model. The reliability and validity test of the model indicated that the model could well distinguish the prognosis and survival of LGG patients. Furthermore, the analyses of immunotherapy, immune microenvironment, as well as functional enrichment were also performed. Finally, we verified the expression of these six prognostic key lncRNAs using real-time polymerase chain reaction (RT-PCR). In conclusion, this study is the first analysis based on cuproptosis-related lncRNAs in LGG and aims to open up new directions for LGG therapy [ABSTRACT FROM AUTHOR]

Vitamin D exerts important extra-skeletal effects, exhibiting an exquisite immune regulatory ability, affecting both innate and adaptive immune responses through the modulation of immunocyte function and signaling. Remarkably, the immune function of working skeletal muscle, which is fully recognized to behave as a secretory organ with immune capacity, is under the tight control of vitamin D as well. Vitamin D status, meaning hormone sufficiency or insufficiency, can push toward strengthening/stabilization or decline of immune surveillance, with important consequences for health. This aspect is particularly relevant when considering the athletic population: while exercising is, nowadays, the recommended approach to maintain health and counteract inflammatory processes, "too much" exercise, often experienced by athletes, can increase inflammation, decrease immune surveillance, and expose them to a higher risk of diseases. When overexercise intersects with hypovitaminosis D, the overall effects on the immune system might converge into immune depression and higher vulnerability to diseases. This paper aims to provide an overview of how vitamin D shapes human immune responses, acting on the immune system and skeletal muscle cells; some aspects of exercise-related immune modifications are addressed, focusing on athletes. The crossroad where vitamin D and exercise meet can profile whole-body immune response and health. [ABSTRACT FROM AUTHOR]

The adaptive immune response induced by SARS-CoV-2 plays a key role in the antiviral process and can protect the body from the threat of infection for a certain period of time. However, owing to the limitations of clinical studies, the antiviral mechanisms, protective thresholds, and persistence of the immune memory of adaptive immune responses remain unclear. This review summarizes existing research models for SARS-CoV-2 and elaborates on the advantages of animal models in simulating the clinical symptoms of COVID-19 in humans. In addition, we systematically summarize the research progress on the SARS-CoV-2 adaptive immune response and the remaining key issues, as well as the application and prospects of animal models in this field. This paper provides direction for in-depth analysis of the anti-SARS-CoV-2 mechanism of the adaptive immune response and lays the foundation for the development and application of vaccines and drugs. [ABSTRACT FROM AUTHOR]

Innate immunity is the first line of defense against invading external pathogens, and pattern recognition receptors (PRRs) are the key receptors that mediate the innate immune response. Nowadays, there are various PRRs in cells that can activate the innate immune response by recognizing pathogen-related molecular patterns (PAMPs). The DNA sensor cGAS, which belongs to the PRRs, plays a crucial role in innate immunity. cGAS detects both foreign and host DNA and generates a second-messenger cGAMP to mediate stimulator of interferon gene (STING)-dependent antiviral responses, thereby exerting an antiviral immune response. However, the process of cGAS/STING signaling is regulated by a wide range of factors. Multiple studies have shown that viruses directly target signal transduction proteins in the cGAS/STING signaling through viral surface proteins to impede innate immunity. It is noteworthy that the virus utilizes these cGAS/STING signaling regulators to evade immune surveillance. Thus, this paper mainly summarized the regulatory mechanism of the cGAS/STING signaling pathway and the immune escape mechanism of the corresponding virus, intending to provide targeted immunotherapy ideas for dealing with specific viral infections in the future. [ABSTRACT FROM AUTHOR]

Currently, conventional neoadjuvant therapy or postoperative adjuvant therapy, such as chemotherapy and radiation therapy, can only bring limited survival benefits to gastric cancer (GC). Median survival after palliative chemotherapy is also low, at about 8-10 months. Immunotargeting is a new option for the treatment of GC, but has not been widely replicated. The highly immunosuppressed tumor microenvironment (TME) discounts the efficacy of immunotherapy for GC. Therefore, new strategies are needed to enhance the immune response of the TME. This paper reviewed the relationship between microorganisms and GC, potential links between microorganisms and immunotherapy and research of microorganisms combined immunotherapy. [ABSTRACT FROM AUTHOR]

Immune responses can severely perturb endoplasmic reticulum (ER) function. As a protein-folding factory and dynamic calcium storage compartment, the ER plays a pivotal role in resisting pathogens and in the development of autoimmune diseases and various other diseases, including cancer, cardiovascular, neurological, orthopedic, and liver-related diseases, metabolic disorders, etc. In recent years, an increasing number of studies have shown that extracellular vesicles (EVs) play important roles in these conditions, suggesting that cells carry out some physiological functions through EVs. The formation of EVs is dependent on the ER. ER stress, as a state of protein imbalance, is both a cause and consequence of disease. ER stress promotes the transmission of pathological messages to EVs, which are delivered to target cells and lead to disease development. Moreover, EVs can transmit pathological messages to healthy cells, causing ER stress. This paper reviews the biological functions of EVs in disease, as well as the mechanisms underlying interactions between ER stress and EVs in multiple diseases. In addition, the prospects of these interactions for disease treatment are described. [ABSTRACT FROM AUTHOR]

The field of immunology is undergoing rapid and dramatic changes. Immunometabolism, a change in metabolic pathways within immune cells, is a key determinant in the activation of immune cells, and intermediates of immunometabolic processes which can influence inflammatory gene expression and play a role in inflammation. Itaconate is one of the most representative metabolites, produced in the tricarboxylic acid cycle (TCA cycle), which links macrophage metabolism, oxidative stress response and immune response to regulate macrophage activity, playing an important role in the function of macrophages. In this paper, we review the mechanisms of the metabolite itaconate and its derivatives in the regulation of macrophage immune metabolism, intending to gain further insight into the role and mechanisms of this metabolite in macrophages and provide new ideas for the mechanisms and treatment of clinical diseases. [ABSTRACT FROM AUTHOR]

Novel coronavirus pneumonia (COVID-19) is spreading worldwide, causing great harm and stress to humans. Since patients with novel coronavirus (SARS-CoV-2) have a high probability of developing acute respiratory distress syndrome (ARDS) in severe cases, the pathways through which SARS-CoV-2 causes lung injury have become a major concern in the scientific field. In this paper, we investigate the relationship between SARS-CoV-2 and lung injury and explore the possible mechanisms of COVID-19 in ARDS from the perspectives of angiotensin-converting enzyme 2 protein, cytokine storm, activation of the immune response, triggering of Fas/FasL signaling pathway to promote apoptosis, JAK/STAT pathway, NF-κB pathway, type I interferon, vitamin D, and explore the possibility of prevention and treatment of COVID-19. To explore the possibility of SARS-CoV-2, and to provide new ideas to stop the development of ARDS in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Cancer is a major threat to human health because of its high mortality, easy recurrence, strong invasion, and metastasis. Photodynamic therapy (PDT) is a promising minimally invasive treatment for tumor. Compared with traditional treatment methods, PDT is less invasive and does not easily damage normal tissues. Most of the effects of this treatment are due to the direct effects of singlet oxygen together with reactive oxygen species. PDT can provide the source of active oxygen for the Fenton reaction, which enhances ferroptosis and also improves the efficacy of PDT in antitumor therapy. Additionally, in contrast to chemotherapy and radiotherapy, PDT has the effect of stimulating the immune response, which can effectively induce immunogenic cell death (ICD) and stimulate immunity. PDT is an ideal minimally invasive treatment method for tumors. In this paper, according to the characteristics of anti-tumor immunity of PDT, some tumor treatment strategies of PDT combined with anti-tumor immunotherapy are reviewed. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, which initially emerged in November of 2019, wreaked havoc across the globe by leading to clinical acute respiratory distress syndrome and continues to evade current therapies today due to mutating strains. Diabetes mellitus is considered an important risk factor for progression to severe COVID disease and death, therefore additional research is warranted in this group. Individuals with diabetes at baseline have an underlying inflammatory state with elevated levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, both of which cause these individuals to have higher susceptibility to SARS- CoV2 infection. The detrimental effects of SARS-CoV-2 has been attributed to its ability to induce a vast cell mediated immune response leading to a surge in the levels of pro-inflammatory cytokines. This paper will be exploring the underlying mechanisms and pathophysiology in individuals with diabetes and insulin resistance making them more prone to have worse outcomes after SARS- CoV2 infection, and to propose an adjunctive therapy to help combat the cytokine surge seen in COVID-19. It will also look at the immunomodulatory effects of glutathione, an antioxidant shown to reduce immune dysregulation in other diseases; Vitamin D, which has been shown to prevent COVID-19 patients from requiring more intensive care time possibly due to its ability to decrease the expression of certain pro-inflammatory cytokines; and steroids, which have been used as immune modulators despite their ability to exacerbate hyperglycemia. [ABSTRACT FROM AUTHOR]

Inflammation is an essential immune response of the host against infections but is often over-activated, leading to a variety of disorders. Autophagy, a conserved degradation pathway, also protects cells by capturing intracellular pathogens that enter the cell and transporting them to the lysosome for clearance. Dysfunctional autophagy is often associated with uncontrolled inflammatory responses during infection. In recent years, more and more research has focused on the crosstalk between autophagy and inflammation. In this paper, we review the latest research advances in this field, hoping to gain insight into the mechanisms by which the body balances autophagy and inflammation in infections and how this mechanism can be used to fight infections better. [ABSTRACT FROM AUTHOR]

Stroke is a multiphasic process, and the initial ischemic phase of neuronal damage is followed by secondary innate and adaptive responses that unfold over days after stroke, offer a longer time frame of intervention, and represent a novel therapeutic target. Therefore, revealing the distinct functions of immune cells in both brain and periphery is important for identification of immunotherapeutic targets for stroke to extend the treatment time window. In this paper an examination of the cellular dynamics of the immune response in the central nervous system (CNS) and periphery provoked by cerebral ischemia is provided. New data is presented for the number of immune cells in brain and spleen of mice during the 7 days following middle cerebral artery occlusion (MCAO). A novel analysis of the correlation among various cell types in the brain and spleen following stroke is presented. It is found that the infiltrated macrophages in the ischemic hemisphere positively correlate with neutrophils which implies their synergic effect in migrating into the brain after stroke onset. It is noted that during infiltration of adaptive immune cells, the number of neutrophils correlate positively with T cells, which suggests neutrophils contribute to T cell infiltration in the stroked brain. Furthermore, the correlation among neurological deficit and various immune cells suggests that microglia and splenic adaptive immune cells (T and B cells) are protective while infiltrating peripheral myeloid cells (macrophage and neutrophils) worsen stroke outcome. Comprehension of such immune responses post cerebral ischemia is crucial for differentiating the drivers of outcomes and also predicting the stroke outcome. [ABSTRACT FROM AUTHOR]

Granzyme B is a renowned effector molecule primarily utilized by CTLs and NK cells against ill-defined and/or transformed cells during immunosurveillance. The overall expression of granzyme B within tumor microenvironment has been well-established as a prognostic marker indicative of priming immunity for a long time. Until recent years, increasing immunosuppressive effects of granzyme B are unveiled in the setting of different immunological context. The accumulative evidence confounded the roles of granzyme B in immune responses, thereby arousing great interests in characterizing detailed feature of granzyme B-positive niche. In this paper, the granzyme B-related regulatory effects of major suppressor cells as well as the tumor microenvironment that defines such functionalities were longitudinally summarized and discussed. Multiplex networks were built upon the interactions among different transcriptional factors, cytokines, and chemokines that regarded to the initiation and regulation of granzyme B-mediated immunosuppression. The conclusions and prospect may facilitate better interpretations of the clinical significance of granzyme B, guiding the rational development of therapeutic regimen and diagnostic probes for anti-tumor purposes. [ABSTRACT FROM AUTHOR]

Immersion vaccination relies on the response of fish mucosa-associated lymphoid tissues, the Crucian carp (Carassius auratus) and Grouper (Epinephelus coioides) were researched in this paper to examine local mucosal immune responses and associated humoral system responses following immersion vaccination. We administered 1.5 × 107 CFU/ml formalin-inactivated Vibrio harveyi cells and measured mucus and serum antibody titers as well as IgM, MHC II mRNA levels in immune organs. The mucosal antibody response preceded the serum response indicating a role for local mucosal immunity in immersion vaccination. IgM and MHC II mRNA levels were relatively greater for the spleen and head kidney indicating the importance and central position of systemic immunity. Expression levels were also high for the gills while skin levels were the lowest. IgM and MHC II mRNA levels were altered over time following vaccination and the hindgut, liver and spleen were similar indicating a close relationship, so the absolute value of r is used to analyze the correlation among different organs immunized. It can be inferred the existence of an internal immune molecular mechanism for Immune synergy hindgut-liver-spleen, from the peak time (14th day), the relative ratio of genes expression in the same tissues between the immunized grouper and the control group (26 times), and Pearson correlation coefficient (0.8<| r |<1). Injection challenges with live V. harveyi indicated that the relative protection rates for the crucian carp and Grouper was basically the same at 44.4% and 47.4%, respectively. It is believe that crucian carp may be used as a substitute for the valuable grouper in immunity experiment, just from aspect of the relative percent survival (RPS) and how it changes with time. But they were not consistent about the IgM mRNA expression between that of crucian carp and grouper after immersion the Vibrio vaccine. [ABSTRACT FROM AUTHOR]

Soluble CD30 (sCD30) is considered to be a marker for the activated immune system in which T cells can damage the allograft. Some studies reported that post-transplant sCD30 can predict early acute rejection and can thereby be used as a biomarker to detect acute rejection. However, several other studies found no relation between post-transplant sCD30 and acute rejection. This meta-analysis study aims to answer this main question of whether sCD30 can help clinicians to monitor transplant recipients. The electronic databases, including PubMed, Web of Science, ProQuest, Embase, Scopus, Google Scholar, the gray literature, and the key journals, were searched for observational studies from 1 January 1990 up to 30 April 2018. Eighteen studies, with a total of 1,453 patients, were included in this paper. With regard to the different measurement times, post-transplant sCD30 was separately analyzed and divided into five groups (i.e., 1, 2, 3, 4 week, and 1 month post-transplant sCD30). All groups indicated a strong association between sCD30 and the acute rejection. The standardized mean difference (SMD) is 1.22 in 1 week, 0.77 in 2 week, 1.11 in 3 week, 1.27 in 4 week, and 0.71 in 1 month groups. The association between sCD30 and acute rejection was consistent across all the subgroup analyses. We found that post-transplant sCD30 had a strong association with acute kidney rejection. We also found that the deceased donors had more association with the high amount of sCD30 than living donors in patients with acute rejection. Finally, we realized that donor type was an important factor leading to the heterogeneous results in the primary studies. [ABSTRACT FROM AUTHOR]

Obesity and its metabolic syndrome, including liver disorders and type 2 diabetes, are a worldwide epidemic and are intimately linked to diet. The gut microbiota interaction has been pointed to as a hot topic of research in the treatment of obesity and related metabolic diseases by influencing energy metabolism and the immune system. In terms of the novel beneficial microbes identified, Akkermansia muciniphila (A. muciniphila) colonizes the mucosa layer of the gut and modulates basal metabolism. A. muciniphila is consistently correlated with obesity. The causal beneficial impact of A. muciniphila treatment on obesity is coming to light, having been proved by a variety of animal models and human studies. A. muciniphila has been characterized as a beneficial player in body metabolism and has great prospects for treatments of the metabolic disorders associated with obesity, as well as being considered for next-generation therapeutic agents. This paper aimed to investigate the basic mechanism underlying the relation of A. muciniphila to obesity and its host interactions, as identified in recent discoveries, facilitating the establishment of the causal relationship in A. muciniphila -associated therapeutic supplement in humans. [ABSTRACT FROM AUTHOR]

Winning the game "Rock, Scissors, Paper" depends on what others do. There is no guarantee that one choice will always win. Does the adaptive immune system use the same intransitive logic to select winners? Here I propose that specialized receptor-ligand pairs, called clicks, initiate contextual cell death to select the best adaptive immune response to a particular challenge. The outcome depends heavily on the phenotypic plasticity of the immune system and upon cell assemblies built from different lineages. These assemblies are self-organizing and use clicks to determine the combination of cells best equipped to defeat a threat. The arrangement is highly adaptive and capable of rapid evolution. Opportunities exist to re-engineer click-based assemblies to produce novel therapeutics. [ABSTRACT FROM AUTHOR]

In the context of allogeneic transplant platforms, human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents one of the latest and most promising curative strategies for patients affected by high-risk hematologic malignancies. Indeed, this platform ensures a suitable stem cell source immediately available for virtually any patents in need. Moreover, the establishment in recipients of a state of immunologic tolerance toward grafted hematopoietic stem cells (HSCs) remarkably improves the clinical outcome of this transplant procedure in terms of overall and disease free survival. However, the HLA-mismatch between donors and recipients has not been yet fully exploited in order to optimize the Graft vs. Leukemia effect. Furthermore, the efficacy of haplo-HSCT is currently hampered by several life-threatening side effects including the onset of Graft vs. Host Disease (GvHD) and the occurrence of opportunistic viral infections. In this context, the quality and the kinetic of the immune cell reconstitution (IR) certainly play a major role and several experimental efforts have been greatly endorsed to better understand and accelerate the post-transplant recovery of a fully competent immune system in haplo-HSCT. In particular, the IR of innate immune system is receiving a growing interest, as it recovers much earlier than T and B cells and it is able to rapidly exert protective effects against both tumor relapses, GvHD and the onset of life-threatening opportunistic infections. Herein, we review our current knowledge in regard to the kinetic and clinical impact of Natural Killer (NK), γδ and Innate lymphoid cells (ILCs) IRs in both allogeneic and haplo-HSCT. The present paper also provides an overview of those new therapeutic strategies currently being implemented to boost the alloreactivity of the above-mentioned innate immune effectors in order to ameliorate the prognosis of patients affected by hematologic malignancies and undergone transplant procedures. [ABSTRACT FROM AUTHOR]

Trained immunity is the enhanced response of the innate immune system to a secondary infection after an initial encounter with a microorganism. This non-specific response to reinfection is a primitive form of adaptation that has been shown to be conserved from plants to mammals. Insects lack an acquired immune component and rely solely on an innate one, and they have expanded it upon traits of plasticity and adaptation against pathogens in the form of immune priming. The recent discoveries of the role of Saccharomyces cerevisiae in the insect's ecology and the ability of this yeast to induce trained immunity in different organisms suggest that insects could have developed mechanisms of adaptation and immune enhancing. Here, we report that two yeast strains of S. cerevisiae , previously shown to induce trained immunity in mammals, enhance resistance to Escherichia coli infection in the paper wasp Polistes dominula. The reduction of injected E. coli load by S. cerevisiae strains was statistically significant in future foundresses but not in workers, and this occurs before and after hibernation. We thus investigated if the effect on E. coli was mirrored by variation in the gut microbiota composition. Foundresses, showing immune enhancing, had statistically significant changes in composition and diversity of gut bacterial communities but not in the fungal communities. Our results demonstrate that S. cerevisiae can prime insect responses against bacterial infections, providing an advantage to future foundress wasps to carry these microorganisms. Understanding the mechanisms involved in the generation of specific and long-lasting immune response against pathogenic infections in insects and the influence of the induction of trained immunity on the commensal gut microbiota could have a major impact on modern immunology. [ABSTRACT FROM AUTHOR]

Phytophthora cinnamomi Rands devastates forest species worldwide, causing significant ecological and economic impacts. The European chestnut (Castanea sativa) is susceptible to this hemibiotrophic oomycete, whereas the Asian chestnuts (Castanea crenata and Castanea mollissima) are resistant and have been successfully used as resistance donors in breeding programs. The molecular mechanisms underlying the different disease outcomes among chestnut species are a key foundation for developing science-based control strategies. However, these are still poorly understood. Dual RNA sequencing was performed in C. sativa and C. crenata roots inoculated with P. cinnamomi. The studied time points represent the pathogen's hemibiotrophic lifestyle previously described at the cellular level. Phytophthora cinnamomi expressed several genes related to pathogenicity in both chestnut species, such as cell wall-degrading enzymes, host nutrient uptake transporters, and effectors. However, the expression of effectors related to the modulation of host programmed cell death (elicitins and NLPs) and sporulation-related genes was higher in the susceptible chestnut. After pathogen inoculation, 1,556 and 488 genes were differentially expressed by C. crenata and C. sativa, respectively. The most significant transcriptional changes occur at 2 h after inoculation (hai) in C. sativa and 48 hai in C. crenata. Nevertheless, C. crenata induced more defense-related genes, indicating that the resistant response to P. cinnamomi is controlled by multiple loci, including several pattern recognition receptors, genes involved in the phenylpropanoid, salicylic acid and ethylene/jasmonic acid pathways, and antifungal genes. Importantly, these results validate previously observed cellular responses for C. crenata. Collectively, this study provides a comprehensive time-resolved description of the chestnut-P. cinnamomi dynamic, revealing new insights into susceptible and resistant host responses and important pathogen strategies involved in disease development. [ABSTRACT FROM AUTHOR]

Immunotherapy has revolutionized cancer treatment by leveraging the immune system's innate capabilities to combatmalignancies. Despite the promise of tumor antigens in stimulating anti-tumor immune responses, their clinical utility is hampered by limitations in eliciting robust and durable immune reactions, exacerbated by tumor heterogeneity and immune evasion mechanisms. Recent insights into the immunogenic properties of host homologous microbial antigens have sparked interest in their potential for augmenting anti-tumor immunity while minimizing off-target effects. This review explores the therapeutic potential of microbial antigen peptides in tumor immunotherapy, beginning with an overview of tumor antigens and their challenges in clinical translation. We further explore the intricate relationship between microorganisms and tumor development, elucidating the concept of molecular mimicry and its implications for immune recognition of tumor-associated antigens. Finally, we discuss methodologies for identifying and characterizing microbial antigen peptides, highlighting their immunogenicity and prospects for therapeutic application. [ABSTRACT FROM AUTHOR]

Background: Nanovaccine treatment is an exciting area of research in immunology and personalized medicine, holding great promise for enhancing immune responses and targeting specific diseases. Their small size allows efficient uptake by immune cells, leading to robust immune activation. They can incorporate immune-stimulating molecules to boost vaccine efficacy. Therefore, nanovaccine can be personalized to target tumor-specific antigens, activating the immune system against cancer cells. Currently, there have been ample evidence showing the effectiveness and potential of nanovaccine as a treatment for cancer. However, there was rare bibliometric analysis of nanovaccine for cancer. Here we performed a bibliometric and visual analysis of published studies related to nanovaccine treatment for cancer, providing the trend of future development of nanovaccine. Methods: We collected the literatures based on the Web of Science Core Collection SCI-Expanded database. The bibliometric analysis was performed via utilizing visualization analysis tools VOSviewer, Co-Occurrence (COOC), Citespace, Bibliometrix (R-Tool of R-Studio), and HitCite. Results: A total of 517 literatures were included in this study. China is the country with the most publications and the highest total local citation score (TLCS). The Chinese Academy of Sciences holds the largest research count in this field and the most prolific author is Deling Kong from Nankai University. The most prominent journal for publishing in this area is Biomaterials. The researches mainly focus on the therapeutic process of tumor nanovaccines, the particle composition and the application of nanovaccines, suggesting the potential hotspots and trends of nanovaccine. Conclusion: In this study, we summarized the characteristics and variation trends of publications involved in nanovaccine, and categorized the most influential countries, institutions, authors, journals, hotspots and trends regarding the nanovaccine for cancer. With the continuous development of nanomaterials and tumor immunotherapy, nanovaccine for cancer provides a research field of significant clinical value and potential application. [ABSTRACT FROM AUTHOR]

With the rapid global spread of COVID-19 and the continuous emergence of variants, there is an urgent need to develop safe and effective vaccines. Here, we developed a novel mRNA vaccine, HC009, based on new formulation by the QTsome delivery platform. Immunogenicity results showed that the prime-boost immunization strategy with HC009 was able to induce robust and durable humoral immunity, as well as Th1-biased cellular responses in rodents or nonhuman primates (NHPs). After further challenge with live SARS-CoV-2 virus, HC009 provided adequate protection against virus infection in hACE2 transgenic mice. Therefore, HC009 could provide significant immune protection against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review. [ABSTRACT FROM AUTHOR]

Immunometabolism has been an emerging hotspot in the fields of tumors, obesity, and atherosclerosis in recent decades, yet few studies have investigated its connection with rheumatoid arthritis (RA). In principle, intracellular metabolic pathways upstream regulated by nutrients and growth factors control the effector functions of immune cells. Dynamic communication and hypermetabolic lesions of immune cells within the inflammatory synovial microenvironment contributes to the development and progression of RA. Hence, targeting metabolic pathways within immune subpopulations and pathological cells may represent novel therapeutic strategies for RA. Natural products constitute a great potential treasury for the research and development of novel drugs targeting RA. Here, we aimed to delineate an atlas of glycolysis, lipid metabolism, amino acid biosynthesis, and nucleotide metabolism in the synovial microenvironment of RA that affect the pathological processes of synovial cells. Meanwhile, therapeutic potentials and pharmacological mechanisms of natural products that are demonstrated to inhibit related key enzymes in the metabolic pathways or reverse the metabolic microenvironment and communication signals were discussed and highlighted. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial damage contributes to apoptosis, oxidative stress, and inflammation, which collectively impact the immune system's function and the tumor microenvironment (TME). These processes, in turn, influence tumor cell growth, migration, and response to treatment. Objective: We conducted a bibliometric analysis to elucidate the complex interactions between mitochondrial damage, the immune system, and the TME. Methods: Data were sourced from the Science Citation Index Core Collection (WoSCC) and analyzed using advanced tools like VOSviewer and Citespace. Our focus was on literature published between 1999 and 2023 concerning the interactions between mitochondrial damage and the TME, as well as immune responses to tumors. The analysis included regional contributions, journal influence, institutional collaborations, authorship, co-cited authors, and keyword citation bursts. Results: Our research encompassed 2,039 publications, revealing an increasing trend in annual output exploring the relationship between mitochondrial damage, TME dynamics, and immune responses. China, the United States, and South Korea emerged as the leading contributors. Prominent institutions included Institut National de la Sante' et de la Recherche Me'dicale, University of Texas System, China Medical University, and Sun Yat-sen University. Key journals in this field are the International Journal of Molecular Sciences, Mitochondrion, and the European Journal of Pharmacology. Liang H and Wallace DC were identified as the most productive and co-cited authors, respectively. Keyword analysis highlighted the critical roles of inflammatory responses, oxidative stress, and the immune system in recent research. Conclusion: This bibliometric analysis provides a comprehensive overview of historical and current research trends, underscoring the pivotal role of mitochondrial damage in the TME and immune system. [ABSTRACT FROM AUTHOR]

Background: Control of buffalo flies (Haematobia irritans exigua, BFs) relies mainly on chemical methods; however, resistance to insecticides is widespread in BF populations. Breeding for resistance to BFs represents a possible alternative, but direct phenotyping of animals is laborious and often inaccurate. The availability of reliable diagnostic biomarker(s) to identify low BF carrier cattle would facilitate rapid and accurate selection for genetic improvement. However, limited information is available regarding differences amongst cattle in host responses to BF infestation. Methods: This study investigated the variation in Brangus cattle serum proteomic profiles before (naïve) and after peak BF exposure, in low (LF) and high BF burden (HF) cattle. Cattle were phenotyped for susceptibility based on BF counts on multiple dates using visual and photographic techniques. The relative abundance of serum proteins in cattle before and after exposure to BFs was analysed using sequential window acquisition of all theoretical fragment ion mass spectrometry (SWATH-MS). Results: Exposure to BFs elicited similar responses in HF and LF cattle, with 79 and 70 proteins, respectively, showing significantly different abundances post exposure as compared to their relevant naïve groups. The comparison of serum samples from naïve HF and LF cattle identified 44 significantly differentially abundant (DA) proteins, while 37 significantly DA proteins were identified from the comparison between HF and LF cattle post-exposure to BFs. Proteins with higher abundance in naïve LF cattle were enriched in blood coagulation mechanisms that were sustained after exposure to BFs. Strong immune response mechanisms were also identified in naïve LF cattle, whereas these responses developed in HF cattle only after exposure to BF. High BF cattle also showed active anticoagulation mechanisms in response to BF exposure, including downregulation of coagulation factor IX and upregulation of antithrombin-III, which might facilitate BF feeding. Conclusion: Underlying differences in the abundance of proteins related to blood coagulation and immune response pathways could potentially provide indirect indicators of susceptibility to BF infestation and biomarkers for selecting more BF-resistant cattle. [ABSTRACT FROM AUTHOR]

Since the discovery of specific immune memory in invertebrates, researchers have investigated its immune response to diverse microbial and environmental stimuli. Nevertheless, the extent of the immune system’s interaction with metabolism, remains relatively enigmatic. In this mini review, we propose a comprehensive investigation into the intricate interplay between metabolism and specific immune memory. Our hypothesis is that cellular endocycles and epigenetic modifications play pivotal roles in shaping this relationship. Furthermore, we underscore the importance of the crosstalk between metabolism and specific immune memory for understanding the evolutionary costs. By evaluating these costs, we can gain deeper insights into the adaptive strategies employed by invertebrates in response to pathogenic challenges. Lastly, we outline future research directions aimed at unraveling the crosstalk between metabolism and specific immune memory. These avenues of inquiry promise to illuminate fundamental principles governing host-pathogen interactions and evolutionary trade-offs, thus advancing our understanding of invertebrate immunology. [ABSTRACT FROM AUTHOR]

Thymic epithelial tumors are rare malignancies with an incidence of 1.7 cases per million people per year. They pose significant management challenges due to their association with autoimmune disorders. In this case report, we present the 21-year history of a patient diagnosed with advanced B2/B3 thymoma and Good's syndrome. The patient achieved a complete and durable response after receiving only two cycles of the immune checkpoint inhibitor Nivolumab. However, this positive outcome was accompanied by the development of severe immune-related myocarditis complicated by reactivation of cytomegalovirus. Moreover, the patient developed a highly uncommon subdiaphragmatic pararectal dissemination of the thymic tumor, which is a condition rarely described in the literature. Despite the success in achieving complete and durable response with immune checkpoint inhibitors, the emergence of immune-related adverse events highlights the potential challenges associated with these treatments, emphasizing the need for careful monitoring and a comprehensive understanding of the intricate interplay between cancer, immune system dysregulations and immunotherapy. [ABSTRACT FROM AUTHOR]

Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as amolecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and αUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the DgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and αUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and αUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the αUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the αUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection. [ABSTRACT FROM AUTHOR]

Background: Left ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs. Materials and methods: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored. Results: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immunerelated genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH. Conclusion: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions. [ABSTRACT FROM AUTHOR]

Background: Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications. Methods: A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases. Results: A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies. Conclusion: Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response. [ABSTRACT FROM AUTHOR]