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This article introduces distance-based paper analytical devices (dPADs) integrated with molecularly imprinted polymers (MIPs) and carbon dots (CDs) for simultaneous quantification of cytokine biomarkers, namely C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6) in human biological samples for diagnosis of cytokine syndrome. Using fluorescent CDs and MIP technology, the dPAD exhibits high selectivity and sensitivity. Detection is based on fluorescence quenching of CDs achieved through the interaction of the target analytes with the MIP layer on the paper substrate. Quantitative analysis is easily accomplished by measuring the distance length of quenched fluorescence with a traditional ruler and naked eye readout enabling rapid diagnosis of cytokine syndrome and the underlying infection. Our sensor demonstrated linear ranges of 2.50-24.0 pg mL-1 (R2 = 0.9974), 0.25-3.20 pg mL-1 (R2 = 0.9985), and 1.50-16.0 pg mL-1 (R2 = 0.9966) with detection limits (LODs) of 2.50, 0.25, and 1.50 pg mL-1 for CRP, TNF-a, and IL-6, respectively. This sensor also demonstrated remarkable selectivity compared to a sensor employing a non-imprinted polymer (NIP), and precision with the highest relative standard deviation (RSD) of 5.14%. The sensor is more accessible compared to prior methods relying on expensive reagents and instruments and complex fabrication methods. Furthermore, the assay provided notable accuracy for monitoring these biomarkers in various human samples with recovery percentages ranging between 99.22% and 103.58%. By integrating microfluidic systems, nanosensing, and MIPs technology, our developed dPADs hold significant potential as a cost-effective and user-friendly analytical method for point-of-care diagnostics (POC) of cytokine-related disorders. This concept can be further extended to developing diagnostic devices for other biomarkers. [ABSTRACT FROM AUTHOR]

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance. [ABSTRACT FROM AUTHOR]

• Cytokine concentration in finger-prick blood VAMS was more variable than in venous. • Room temperature had the most significant changes in concentration over time. • The optimal storage temperature differed for each analyte. • Incomplete extraction of 6 spiked cytokines may indicate cytokine-VAMS interaction. Dried blood spots (DBS) collected on filter paper such as Guthrie cards are stored for years at room temperature. The assumption is that once dried, the samples remain stable and quantifiable indefinitely since the metabolites these were initially designed to measure, are known for their extended stability. The concentration of other blood proteins such as cytokines, however, are known to vary with storage even in liquid samples stored at −80 °C for extended periods of time. We sought to determine if cytokines are stable for up to 5 months when stored as a dried blood sample using volumetric absorptive microsampling (VAMS) devices. To test this, blood was collected from 4 healthy participants, spiked with recombinant cytokines, and collected into 30 µL VAMS devices. These prepared VAMS devices were stored at room temperature, 4 °C, or −20 °C for up to 5 months and matching VAMS liquid extracts were stored at −80 °C for the same period of time. At each timepoint, the samples were extracted from the VAMS devices and the extracts were analysed by Luminex® for quantification of up to 31 cytokines. These methods were also tested in a remote clinical study over a period of up to 8 months. Cytokine analysis revealed that room temperature, the current standard for DBS and VAMS storage, performed the poorest out of all storage temperatures with significant losses in 13/21 analytes compared to 4 °C at 5 months. Storage at 4 °C or colder performed well for the majority of analytes tested, however out of those, the optimal storage temperature differed for each analyte. There were a small number of analytes that performed poorly regardless of storage conditions and for fractalkine, this was found to be caused by inefficient recovery during extraction. Cytokine concentrations from finger-prick samples were also found to be much more variable that those in venous blood samples. Our results highlight the need to understand the stability of analytes of interest before committing to longitudinal collection and storage of samples in VAMS devices. These data give confidence that storage at 4 °C or colder was beneficial for cytokine stability. Wherein 25/31 cytokines were quantifiably stable at −20 °C when stored for 3 months and 17/21 were quantifiably stable after 5 months when stored at 4 °C. [ABSTRACT FROM AUTHOR]

The diverse physicochemical properties of polymers make them perfect candidates for developing biosensor elements when combined with porous substrates. For example, microfluidic channels, valves, reservoirs and biorecognition elements have been proposed that rely on filling the cavities of porous cellulose with different polymers. Yet, highly concentrated polymers are often too viscous to dispense them with precision using conventional printing methods. This increases the manufacturing variability, which degrades the performance of the biosensors. Here this issue is solved with a new method for infusing porous materials (filter paper) with concentrated polymers (PSS) that circumvents the dropwise addition of highly viscous reagents. The resulting films contain homogenously distributed polymers, which reduces the intra- and inter-batch variabilities of biosensors based on dispensing nanoparticles from the reservoirs. The proposed method was utilized to develop immunosensors for detecting the cytokines IL-6 and IL-5 in aerosols, which were trapped by the polypropylene layer of a surgical face mask (limit of detection 10−2 pg·mL−1). Using this approach, we were able to detect elevated levels of airways cytokines when exacerbated COPD patients and eosinophilic asthma patients wore the face mask for 30 min. The results shown here pave the way for upscaling the manufacturing of paper-based nanoparticle biosensors, which is a crucial step towards their future commercialization. [Display omitted] • Nanoparticle reservoirs are fabricated by infusing filter paper with polystyrene sulfonate • The proposed method reduces the intra- and inter-batch fabrication variability • Biosensors against IL-6 and IL-5 in aerosols are developed • Non-invasive detection of airways cytokines in patient samples is demonstrated [ABSTRACT FROM AUTHOR]

Abstract In this study, levels of inflammatory protein biomarkers in venous plasma, plasma derived from capillary blood from the earlobe, and capillary plasma stored as dried plasma spots (DPS) were compared. Samples from 12 male individuals were assessed with a panel of 92 inflammation-related proteins using multiplex proximity extension assay. Correlations between sample types varied greatly between analytes. A high correlation of ρ > 0.8 was observed between capillary plasma and DPS for 32 analytes. At this level of correlation, 13 analytes correlated between venous and capillary plasma and 5 analytes in the comparison of venous blood with DPS. Highlights • Measurement of an inflammation protein panel in three sample sources. • Earlobe plasma as a less invasive alternative sample source than venous plasma. • Protein measurement in capillary plasma stored as dried plasma spots (DPS). • Correlation value of ρ > 0.8 between capillary earlobe plasma and DPS for 32 analytes. • Correlation value of ρ > 0.8 between venous and capillary earlobe plasma for 13 analytes. [ABSTRACT FROM AUTHOR]

Simple Summary: This research studied how three types of proteins, called interleukins (namely 8, 17A and 33), are present in the blood of healthy people and people with colon cancer. Colon cancer is a disease that affects the large intestine. The paper looked at 82 people, 42 of whom had colon cancer and 40 of whom did not. The researchers divided the cancer patients into four groups based on how severe their cancer was. The study measured the amount of interleukins in the blood of each person using a special test. The paper analyzed the results of the test, considering the age, gender, and cancer stage of each person. The results showed that younger people, and those with less severe cancer had more interleukins in their blood. The paper also found that two of the interleukins (8 and 17A) were higher in the cancer group, while one of them (33) was higher in the healthy group. The study also found that the interleukins were related to each other in both groups. This research concluded that the interleukins might help detect colon cancer and predict how it will progress. This paper could help improve the diagnosis and treatment of colon cancer. This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome. [ABSTRACT FROM AUTHOR]

The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin® and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin® similarly secreted IL-6, TNF-α, IL-1β, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals. [ABSTRACT FROM AUTHOR]

Simple Summary: The microenvironment of hepatocellular carcinoma is a really complex milieu, containing a wide variety of cells with specific tasks, belonging to both the mesenchimal and immunitary systems, the extracellular matrix, growth factors, proinflammatory cytokines, and translocated bacterial products. This intricate environment represents a source of potential targets in order to establish a wide and multitask therapeutic strategy for hepatocellular carcinoma. Hepatocellular carcinoma is a malignant tumor that originates from hepatocytes in an inflammatory substrate due to different degrees of liver fibrosis up to cirrhosis. In recent years, there has been growing interest in the role played by the complex interrelationship between hepatocellular carcinoma and its microenvironment, capable of influencing tumourigenesis, neoplastic growth, and its progression or even inhibition. The microenvironment is made up of an intricate network of mesenchymal cells, immune system cells, extracellular matrix, and growth factors, as well as proinflammatory cytokines and translocated bacterial products coming from the intestinal microenvironment via the enterohepatic circulation. The aim of this paper is to review the role of the HCC microenvironment and describe the possible implications in the choice of the most appropriate therapeutic scheme in the prediction of tumor response or resistance to currently applied treatments and in the possible development of future therapeutic perspectives, in order to circumvent resistance and break down the tumor's defensive fort. [ABSTRACT FROM AUTHOR]

Interleukin‐41 (IL‐41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin‐like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti‐inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL‐41, the relationship between IL‐41 and diseases, the effects of IL‐41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL‐41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL‐41 related preparations for lung protection and smoking cessation are interesting research fields. [ABSTRACT FROM AUTHOR]

Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico‐amygdala circuit, lowers sensitivity to rewards in the cortico‐striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self‐medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress‐related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapeutic options for GEP-NETs are very limited, and at the same time, the incidence of these cancers is increasing. The evidence has shown that multiple neoplasms can be successfully treated with immune checkpoint inhibitors such as PD-1/PD-L1 inhibitors. Crucial to determining a patient's response to immunotherapy is access to the tumor microenvironment. Currently, there is no consistency regarding the future role of TME and immunotherapy in GEP-NETs. Thus, this review points to the solution in selecting a concrete patient group that, based on tumor features can benefit from immunotherapy. Neuroendocrine neoplasms (NENs) are a heterogenous and recurrent group of malignancies originating from neuroendocrine secretory cells diffused on all parts of the human body. Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) account for most NENs. Considering the abundance of possible origins, locations, and tumor specifications, there is still no consensus about optimal treatment options for these neoplasms. In light of the escalating immunotherapeutic approaches, it is crucial to define indications for such therapy in GEP-NETs. Bearing in mind the significance of pathophysiological mechanisms and tumor microenvironment (TME) impact on carcinogenesis, defining TME structure and correlation with the immune system in GEP-NETs appears essential. This paper aimed to assess the characterization of the tumor immune microenvironment for a better understanding of the possible therapeutic options in GEP-NETS. The authors performed a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 3800 articles identified through database searching, 292 were assessed for eligibility. Ultimately, 28 articles were included in the qualitative synthesis. This paper sums up the research on the immune cell infiltrates, immune checkpoint expression, cytokine profile, neoangiogenesis, and microbiome in the TME of GEP-NETs. [ABSTRACT FROM AUTHOR]

Analysis of cytokines levels in human serum is critical as it can be a "symptom diagnostic biomarker" in COVID-19, giving real-time information about human health status. Here, we present the construction and performance of a low-price immunosensor (∼US$0.428 per test) based on microfluidic paper-based system to detect cytokine for predicting the health status of COVID-19 patients. Interleukin-6 (IL-6) was selected as the detection model for the close relationship between IL-6 and COVID-19. The assay, which we integrated into foldable paper system, leverages the magnetic immunoassay, the streptavidin-horseradish peroxidase (HRP) associated with tetramethyl benzidine/hydrogen peroxide (TMB/H 2 O 2) to amplify the signal for electrochemical readout. To improve the sensitivity of cytokine detection, a hybrid of gold nanoparticles (AuNPs) and polypyrrole (PPy) hydrogel was modified on the working electrode to increase the conductivity and improve the electron transfer rate. With our prototypic origami paper-based immunosensor operated in differential pulse voltammetry (DPV) mode, we achieved excellent results with a dynamic range from 5 to 1000 pg/mL and a lower detection limit (LOD) of 0.654 pg/mL. Furthermore, we evaluated the capability of the clinical application of the proposed immunosensor using human serum samples from a hospital. The results indicate that our proposed immunosensor has great potential in early diagnosing high-risk COVID-19 patients. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is a disturbance of neurodevelopment with a complicated pathogenesis and unidentified etiology. Many children with ASD have a history of "allergic symptoms", often in the absence of mast cell (MC)-positive tests. Activation of MCs by various stimuli may release molecules related to inflammation and neurotoxicity, contributing to the development of ASD. The aim of the present paper is to enrich the current knowledge on the relationship between MCs and ASD by discussing key molecules and immune pathways associated with MCs in the pathogenesis of autism. Cytokines, essential marker molecules for MC degranulation and therapeutic targets, are also highlighted. Understanding the relationship between ASD and the activation of MCs, as well as the involved molecules and interactions, are the main points contributing to solving the enigma. Key molecules, associated with MCs, may provide new insights to the discovery of drug targets for modeling inflammation in ASD. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is one of common pulmonary complications of connective tissue disease (CTD), which seriously affects quality of life and significantly increases risk of death of patients with CTD. However, related immune mechanism of CTD-ILD is not clear yet. This paper systematically reviews involvement of various cytokines in pathogenesis of CTD-ILD. Pathogenesis of CTD-ILD and correlation between cytokines and clinical indicators were discussed from cell level, animal model and clinical trials, to investigate whether cytokines can be targeted for treatment of CTD-ILD to help guide future research and clinical practice. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune-mediated chronic inflammatory skin disease that affects 2% to 3% of the world's population. It is widely assumed that immune cells and cytokines acting together play a crucial part in the pathophysiology of psoriasis by promoting the excessive proliferation of skin keratinocytes and inflammatory infiltration. Interleukins (ILs), as a critical component of cytokines, have been closely associated with the pathogenesis and progression of psoriasis. This review summarizes the current contribution of ILs to psoriasis and describes the role each IL performs in psoriasis. Furthermore, the paper presents the therapeutic effects and application prospects of biologics developed for ILs in clinical treatment and experiments. The study aims to further the research on ILs in the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

In mammals, chemokines are a superfamily of cytokines that regulate cell migration or exert direct antimicrobial activity. The presence and organization of four invariant cysteine residues within the mature protein sequence can classify chemokines into four major subfamilies: CXC, CC, CX3C, and XC. In teleost, a novel subfamily of chemokines named CX has been identified. Since the first report of a CC chemokine (CK1) in rainbow trout in 1998, the number of identified chemokine genes in different fish species has expanded dramatically. In this paper, we reviewed the chemokine genes that have been identified so far in teleost fish and their tissue expressions and responses post-stimulation. We also discussed the functions of fish chemokines based on currently available information and compared them to human chemokines. Additionally, we predicted the structures of trout chemokines for the first time, and we found that the structures of trout chemokines share significant similarities. Finally, the adjuvant effects of fish chemokines in aquaculture were also reviewed. Overall, this review will give us a better understanding of the chemokines of teleost fish. [ABSTRACT FROM AUTHOR]

Depression represents a mood disorder and is considered to be one of the most common mental disorders in general. World Health Organization estimates that depression will be the leading cause of disability-adjusted life years, until 2030. Depression is a complex heterogeneous disorder where immune system and its regulation play an important role. Innate and adaptive immunity mechanisms are included, along with processes of immune activation and suppression. The expression of humoral factors of innate immunity, especially pro-inflammatory cytokines, is increased, whereas the intensity of cellular immune mechanisms, primarily T cells and NK cells, are impaired. The influence of pro- inflammatory cytokines on depression is reflected in their effect on certain enzymes and ensuing reduction of neurotransmitters serotonin and dopamine. They also affect the neuroendocrine function in central nervous system, resulting in increase of cortisol levels and inactivation of glucocorticoid receptors in the periphery, which leads to neurodegeneration and decrease in neurotransmitter production. Certain cytokines affect neuroplasticity through the decreasing of concentration of neurotrophic brain factor and induction of brain cell apoptosis. The results are often contradictory talking about mechanisms of adaptive immunity. On one hand, an increased activity of Tlymphocytes is observed, while on the other, there are evidence of spontaneous apoptosis and impaired function of these cellsin depression. In addition, neuroprotective role of autoreactive and regulatory T cells in prevention of depression has also been demonstrated. The aim of this paper is to analyze the current knowledge on the role of immune mechanisms in the pathogenesis of depression. [ABSTRACT FROM AUTHOR]

Simple Summary: Photodynamic therapy (PDT) is a cancer treatment that uses photogenerated reactive oxygen species (ROS) to damage target cells. The unique mechanism of action of PDT involves the systemic or local administration of a photosensitizing compound (photosensitizer), which is then activated by light of a specific energy. PDT induces a very strong local inflammatory response. A number of adaptive mechanisms are induced within the tumor, related to increased amino acid metabolism and damage to lymphatic vessels. In this review, we are describing the adaptive immune response induced by ROS and generated by PDT. Cancer is one of the most significant causes of death worldwide. Despite the rapid development of modern forms of therapy, results are still unsatisfactory. The prognosis is further worsened by the ability of cancer cells to metastasize. Thus, more effective forms of therapy, such as photodynamic therapy, are constantly being developed. The photodynamic therapeutic regimen involves administering a photosensitizer that selectively accumulates in tumor cells or is present in tumor vasculature prior to irradiation with light at a wavelength corresponding to the photosensitizer absorbance, leading to the generation of reactive oxygen species. Reactive oxygen species are responsible for the direct and indirect destruction of cancer cells. Photodynamically induced local inflammation has been shown to have the ability to activate an adaptive immune system response resulting in the destruction of tumor lesions and the creation of an immune memory. This paper focuses on presenting the latest scientific reports on the specific immune response activated by photodynamic therapy. We present newly discovered mechanisms for the induction of the adaptive response by analyzing its various stages, and the possible difficulties in generating it. We also present the results of research over the past 10 years that have focused on improving the immunological efficacy of photodynamic therapy for improved cancer therapy. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysiological injury of the body, and increased mortality in populations with DM upon infections. Starting with the change of natural immune system in patients with DM, this paper focused on the enhanced severity of infections in DM and the underlying innate immune alterations in preclinical and clinical studies, aiming to better understand the influence of DM on the susceptibility, pathophysiology, and clinical outcomes in infections. [ABSTRACT FROM AUTHOR]

It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1β. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted. In vitro assessment of microglia-released cytokines upon viral infection has been more frequent since 2015 and has focused more on pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Background: In vitro stimulation of whole blood or isolated blood cells with specific antigens is used for several purposes. Immediately following incubation with antigens, samples have to be centrifuged to stop the reactions by remaining cells and the supernatant refrigerated or analysed directly to preserve the analytes of interest, which makes samples difficult to prepare outside laboratories. We have tested whether spotting whole blood on filter paper after activation can be used in one of the tests for Mycobacterium tuberculosis infection (MTI), the QuantiFERON®-TB Gold In Tube test (QFT), where the spotting technique can make it suitable for use in locations without facilities like a centrifuge and a refrigerator. Materials and methods: Samples from 22 individuals undergoing screening for MTI and 10 healthy controls were incubated, centrifuged and IFN-γ measured by Enzyme-linked immunosorbent assay (ELISA), as described in the kit insert. In parallel, activated blood was spotted on filter paper (Schleicher & Schuell) and dried. The dried blood spot samples were analysed for 21 inflammatory markers with an in-house assay based on Luminex technology. Results: Our multiplex measurements of inflammatory markers in samples from suspected MTI patients confirmed the IFN-γ findings in the QFT. IL-2, GM-CSF, IL-5, and IL-1β were also found as useful markers for MTI. We were not able to distinguish between active tuberculosis and latent MTI. Conclusion: Applying blood on filter paper after incubation makes in vitro stimulation tests feasible in locations where heat and electricity is unavailable. [ABSTRACT FROM AUTHOR]

Abstract: Total hip-joint arthroplasty is performed in increasing numbers where it translates to about 0.16–0.2% of population per year in industrial countries. In most cases, an implant is a metallic component articulating with a metal, ceramic or poly-ethylene liner as seen in the case of hip, knee and spine. The metal implants release ions in vivo. Therefore, there is a need to study metallic implants and ions released as a result. Toxic concentrations of ions can lead to many adverse physiological effects, including cytotoxicity, genotoxicity, carcinogenicity, and metal sensitivity. There is a need to map ion concentrations establishing boundaries between normal and toxic levels; which however, does not exist. Reference levels of ion concentrations in body fluids and tissues determined by many studies are compiled, reviewed, and presented in this paper. The concentrations of ions released from different alloys, including cobalt, chromium, nickel, molybdenum titanium, aluminum, and vanadium, are presented in this paper. This paper reviews the literature pertaining to clinical data on metal ion concentrations in patients with metal joint prostheses, and laboratory data on the physiological effects of the metals. [Copyright &y& Elsevier]

We examined the utility of dried blood on filter paper for the source of cytokine messenger RNA (mRNA). Total RNA was isolated from the dried blood of mice infected with Plasmodium yoelii, and cDNA was amplified by reverse transcription-polymerase chain reaction (RT-PCR). As a reference, we extracted total RNA from peripheral blood collected at the same time as the preparation for dried blood. There was no difference in cytokine mRNA expression between the two sources; the dried blood on filter paper and the peripheral blood. Th1 cells, Th2 cells, and monocytes/macrophages derived cytokine mRNAs in the dried blood from infected mice were detected, and the increase of some of the cytokines mRNAs after infection was also observed. These results suggested that the dried blood on filter paper is satisfactory RNA source for immunological examination in field-based studies. [Copyright &y& Elsevier]

The article discusses the use of diagnostic biomarkers for prediction of adverse early pregnancy outcomes. Topics mentioned include the use of a biomarker for reduction of clinical burden of pregnancy of unknown location cases, the controversies surrounding the use of biomarkers, such as human chorionic gonadotrophin and progesterone, and the categorization of biomarkers in early pregnancy based on their biological origin.

Ischaemic postconditioning (brief periods of ischaemia alternating with brief periods of reflow applied at the onset of reperfusion following sustained ischaemia) effectively reduces myocardial infarct size in all species tested so far, including humans. Ischaemic postconditioning is a simple and safe manoeuvre, but because reperfusion injury is initiated within minutes of reflow, postconditioning must be applied at the onset of reperfusion. The mechanisms of protection by postconditioning include: formation and release of several autacoids and cytokines; maintained acidosis during early reperfusion; activation of protein kinases; preservation of mitochondrial function, most strikingly the attenuation of opening of the mitochondrial permeability transition pore (MPTP). Exogenous recruitment of some of the identified signalling steps can induce cardioprotection when applied at the time of reperfusion in animal experiments, but more recently cardioprotection was also observed in a proof-of-concept clinical trial. Indeed, studies in patients with an acute myocardial infarction showed a reduction of infarct size and improved left ventricular function when they underwent ischaemic postconditioning or pharmacological inhibition of MPTP opening during interventional reperfusion. Further animal studies and large-scale human studies are needed to determine whether patients with different co-morbidities and co-medications respond equally to protection by postconditioning. Also, our understanding of the underlying mechanisms must be improved to develop new therapeutic strategies to be applied at reperfusion with the ultimate aim of limiting the burden of ischaemic heart disease and potentially providing protection for other organs at risk of reperfusion injury, such as brain and kidney. [ABSTRACT FROM PUBLISHER]

The article presents abstracts of neuropsychiatric research. They include "Psychotic-like experiences in a community sample of adolescents: associations with distress, depression and functioning," "Association of cytokines and cognitive functioning in the elderly general population," and "Reduced psychoacoustic sensitivity to auditory temporal stimulation in schizophrenia reflects cytoarchitecturally specific changes in auditory cortex."

Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)- α (−238 G/A and −308 G/A), TNF- β (+252 G/A), and interleukin (IL)-1 β (−511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF- β (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0·04, odds ratio = 3·6, 95% confidence interval 1·1–11·1), while no significant association was detected for the other SNPs. The distribution of the TNF- β (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the TNF- β (+252) G/G phenotype than in those with the G/A or A/A phenotype (11·9 ± 4·9 vs. 6·8 ± 4·9 and 3·7 ± 2·8 per 105 peripheral blood mononuclear cells; P = 0·02 and P < 0·001, respectively). These findings suggest that the SNP located at TNF- β (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins. [ABSTRACT FROM AUTHOR]

Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms-like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF- α. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8·5–27·2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)- γ producing CD4+ T cells and in production of IFN- γ. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells. [ABSTRACT FROM AUTHOR]

Intravenous (IV) anti-D and IV immunoglobulin (IVIG) slow the Fc γ receptor (Fc γR)-mediated destruction of antibody-coated platelets in patients with immune thrombocytopenic purpura (ITP). This pilot study explored the mechanism of these immunoglobulin preparations by measuring interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor  α (TNF α), before and after infusion and by assessing the effect of Fc γRIIa and Fc γRIIIa polymorphisms on both cytokine and haematologic responses to anti-D. Following IVIG, only IL-10 was increased at 2 h and MCP-1 on day 7 ( P < 0·05). In contrast, 2 h after anti-D infusion, plasma levels of all four cytokines were increased ( P < 0·01); five of six patients with the highest MCP-1, IL-6 and TNF α levels had chills. Higher IL-10 levels correlated with platelet increases at 24 h and haemoglobin decreases at day 7 ( P < 0·025). Patients with the Fc γRIIa-131HH genotype had significantly higher MCP-1, IL-6 and TNF α levels. Patients with the Fc γRIIIa-158VF genotype had higher platelet increments at day 7 ( P < 0·05). Soluble CD16 (sCD16) was increased 2 h after IV anti-D; day 7 levels correlated with day 7 haemoglobin decreases ( P < 0·01). In conclusion, the relationship of Fc γRIIa and Fc γRIIIa polymorphisms with both cytokine levels and platelet increments implicated these receptors in responses to anti-D and supported different mechanisms of Fc γR interaction to those seen with IVIG. [ABSTRACT FROM AUTHOR]

Myeloma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to model in vitro the interactions between myeloma and endothelium, and treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs, phosphodiesterase-4 inhibitors). Flow cytometry and enzyme-linked immunosorbent assay were used to assess production of two key cytokines – vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) – and apoptosis in co-cultured HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs, while IL-6 was almost exclusively produced by endothelial cells. In co-culture, there was significant up-regulation of VEGF and IL-6 production compared with the sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited production of both cytokines in co-cultures, with CC-10004 being more potent than CC-1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co-cultured myeloma cells was significantly lower than in those cultured separately, suggesting that co-culture partially protected myeloma cells from drug-induced apoptosis. This protective effect was probably due to IL-6 produced by endothelial cells in co-culture as addition of anti-IL-6 neutralizing antibody, but not anti-VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their anti-myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL-6 production by interacting myeloma and endothelium and induction of myeloma cell apoptosis. [ABSTRACT FROM AUTHOR]

Prolonged quiescence of haematopoietic stem cells has been proposed to support durable haematopoiesis through clonal succession. Genetic experiments in mice have implicated the cyclin-dependent kinase inhibitor (cdki) p21Waf1 in sustaining stem cell quiescence, and the cdki p27Kip1 in inhibiting the expansion of more mature progenitor cells. The expression of these inhibitory proteins in human haematopoietic stem cell candidates has not hitherto been studied. We describe a rare subpopulation (3 × 10−7 umbilical cord mononuclear cells) of lineage-negative cells that exhibited sustained resistance over months to cytokine-induced cycling, and characterized the expression of p21Waf1 and p27Kip1 proteins in these cells. Whereas p27Kip1 was uniformly expressed in these cells, the expression of p21Waf1 in this population and in lineage-negative CD34+ cells was variable. For this rare subset of cells exhibiting prolonged quiescence, p21Waf1 may be dispensable and p27Kip1 necessary for growth arrest. [ABSTRACT FROM AUTHOR]

T-cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T-cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four-colour flow cytometry was applied to study the surface bound molecules TCR α β, CD28, CD152 and CD154 involved in T-cell signalling and the signal transduction molecules CD3 ζ, p56lck, p59fyn, ZAP-70 and phosphatidyl-inositol-3 kinase (PI3-k) as well as the intracellular cytokines interferon- γ (IFN- γ), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non-stimulated and superantigen-stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3 ζ, p56lck, ZAP-70 and PI3-k. The level of intracellular T-cell cytokines (IFN- γ, IL-2 and IL-4) was normal or increased in non-stimulated cells but activation-induced cytokine production was impaired. These results illustrated profound and multiple T-cell signalling defects, from the surface and down-stream, consistent with involvement of a master T-cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune-based therapeutic approaches and when applying new emerging technologies that aim to restore T-cell functions. [ABSTRACT FROM AUTHOR]

This paper reports for the first time the immunomodulatory and cytotoxic effects of two previously isolated compounds from the stem of Peltophorum pterocarpum and characterized as bergenin (1) and cinchonain Ia (2). The immunomodulatory capacity of these two compounds was assessed based on their ability to inhibit IL-2 release from RAW264.7 cells. The results demonstrated that cinchonain Ia (2) possesses distinctly immunomodulatory effects in vitro since this compound strongly inhibited IL-2 cytokine level (at concentrations of 4.0 and 0.8 μg/mL) (P<0.01 and P<0.05), while it was increased up to 8.84 time at the 100 μg/mL concentration. Additionally, compound 2 showed a weak cytotoxic effect against 5 human cancer cells (A549, Huh-7, T24, 8505, and SNU-1) with the IC50 values between 39.19 g/mL and 60.44 μg/mL. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that circRNAs are involved in the pathogenesis of osteoarthritis (OA) by affecting various fundamental cellular characteristics of chondrocytes. The purpose of this paper is to investigate the role and regulatory mechanism of hsa_circ_0020014 (circ_0020014) in chondrocytes of OA. Methods: The inflammatory cytokine interleukin 1 beta (IL-1β) was used to stimulate human chondrocytes. Cell viability, proliferation, and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-Ethynyl-2′-deoxyuridine (EdU), and flow cytometry assays. Several protein levels were determined by western blotting (WB). Levels of inflammatory cytokines and malondialdehyde (MDA) were determined by enzyme-linked immunosorbent assay (ELISA). Relative expression of circ_0020014 was estimated by real-time polymerase quantitative chain reaction (RT-qPCR). Bioinformatics prediction combined with dual-luciferase reporter, RIP and RNA pull-down assays were done to probe into the regulatory mechanism of circ_0020014. Results: Circ_0020014 was overexpressed in OA patient-derived articular cartilages and IL-1β-stimulated chondrocytes. Silencing of circ_0020014 lighted IL-1β-prompted chondrocyte proliferation repression, apoptosis, inflammation, and oxidative stress. Mechanically, circ_0020014 functioned as a miR-24-3p molecular sponge to regulate cathepsin B (CTSB) expression. Furthermore, miR-24-3p inhibition alleviated circ_0020014 knockdown-mediation repression of IL-1β-urged chondrocyte injury. In addition, CTSB overexpression whittled miR-24-3p upregulation-mediated suppression of IL-1β-urged chondrocyte injury. Conclusion: Our findings demonstrated that the circ_0020014/miR-24-3p/CTSB axis was associated with IL-1β-prompted chondrocyte injury, supporting the involvement of circ_0020014 in the OA pathogenesis. Highlights: A significant upregulation of circ_0020014 was observed in OA patient-derived articular cartilages. Inhibition of circ_0020014 lessened IL-1β-urged chondrocyte injury. Circ_0020014 could interact with miR-24-3p to mediate CTSB expression. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the significant diseases that threaten the survival of men worldwide, with the progression of androgen deprivation therapy, become much rely on it, finally, developed into castration-resistant prostate cancer (ADT). In western countries, ranks second in incidence, and in China, with increasing lifespan, the incidence of prostate cancer is rising steadily. Although chemotherapy agents, such as taxane, have achieved some efficacy, treatment failure still occur. As sensitivity of hormone levels change, the disease can progress to castrate-resistant prostate cancer. Because of the poor efficacy of traditional surgery, endocrine therapy, radiation therapy, and chemotherapy, the treatment options for castrate-resistant prostate cancer are limited. Advanced prostate cancer can progress on immunotherapy, and thus, bio -immunotherapy targeting the unique, prostate microenvironment is an important option. In this paper, we systematically revealed the role of three types of bio-immunotherapies (immune checkpoint inhibitors, tumors, vaccines, cytokines) in castrate-resistant prostate cancer, providing a reference for clinical treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) is a disorder that impairs the formation of the relationship between mother and child, and reduces the quality of life for affected women to a functionally significant degree. Studying markers associated with PPD can help in early detection, prevention, or monitoring treatment. The purpose of this paper is to review biomarkers linked to PPD and to present selected theories on the pathogenesis of the disease based on data from biomarker studies. The complex etiology of the disorder reduces the specificity and sensitivity of markers, but they remain a valuable source of information to help clinicians. The biggest challenge of the future will be to translate high-tech methods for detecting markers associated with postpartum depression into more readily available and less costly ones. Population-based studies are needed to test the utility of potential PPD markers. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

The development of pre-eclampsia is associated with immunological interactions between the foreign maternal and fetal tissues, which are characterized by a predominance of the influence of type 1 T-helper cells, leading to increased production of highly aggressive pro-inflammatory cytokines. However, the mechanism of cellular-humoral immune and cytokine changes leading to the manifestation of pre-eclampsia is not fully understood and no corrective measures have been developed. Purpose. To investigate the changes in the cellular-humoral immunity and cytokine profile in a cervical mucus of pregnant women at high risk for developing PE and to find out the effectiveness of the proposed secondary prevention of PE in the normalization of these indicators. Method and Materials. The main group (MG) consisted of 91 pregnant women with risk factors for pre-eclampsia who had impaired blood flow in the uterine spiral arteries at 18-20 weeks of pregnancy. Among them, 59 patients (MG-II) received secondary prevention of pre-eclampsia from 18-20 weeks until delivery using metformin, vitamin D3, and corvitin, while the remaining 32 patients (MG-I) declined preventive measures. The control group (CG) consisted of 30 healthy pregnant women. The research was regulated by the rules of humane treatment of patients in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the international recommendations of the Helsinki Declaration on Human Rights, the Convention of the Council of Europe on Human Rights and Biomedicine, and the laws of Ukraine. TNF-α, INFγ and IL-10 levels were determined in cervical mucus by enzyme-linked immunosorbent assay (ELISA); peripheral blood lymphocyte CD3+, CD4+, CD8+, CD16+, CD22+ levels were assessed by indirect immunofluorescence. The CD4/CD8 ratio was calculated as an immunoregulatory index. Blood serum immunoglobulin (Ig) levels were determined by competitive enzyme-linked immunosorbent assay (A, M, and G). The concentration of circulating immune complexes (CIC) in blood serum was measured by the immunoturbidimetric assay. The data were analyzed by mathematical-statistical methods, calculating the mean (M), variance (σ), and standard error (m), applying Student's t-test, and performing correlation analysis using the statistical program «STATISTICA» (StatSoft Inc., USA). The paper is an excerpt from the initiative scientific research project of the Department of Obstetrics and Gynecology № 2 of the Poltava State Medical University entitled «Optimization of approaches to management of pregnancy in women at high risk of obstetric and perinatal pathology» (state registration number 0122U201228, duration: 10.2022-09.2027). Results. In women at high risk of developing pre-eclampsia (MG-I), a significant decrease in the concentration of T helper cells (CD4+), an increase in T suppressor/killer cells (CD8+), a decrease in the immunoregulatory index, a decrease in B cells (CD22+) and an increase in CIC were observed. In addition, CIC greater than 100 IU/ml strongly correlated with the development of pre-eclampsia. IgM levels were significantly elevated in women with pre-eclampsia, indicating possible trophoblastic stimulation of their immune system, while IgG levels were significantly reduced. Women with pre-eclampsia had a significant predominance of pro-inflammatory cytokines and a deficiency of anti-inflammatory cytokines. In women of the MG-II group who received the proposed complex of secondary prevention of pre-eclampsia, the content of T-helper cells (CD4+) and T-suppressor/killer cells (CD8+) was normalized. The immunoregulatory index increased significantly, and the number of CD22+ cells was about the level observed in healthy pregnant women. The concentrations of IgA and IgG increased to the levels observed in the control group, while the level of IgM decreased. The level of CIC decreased in pregnant women with MG-II, in contrast to the levels observed in women with MG-I. The levels of pro-inflammatory cytokines INF-γ and TNF-α decreased after preventive treatment. However, the levels of the antiinflammatory cytokine IL-10 increased significantly in MG-II, leading to a significant reduction in the TNF-α/IL-10 ratio (p<0.001). Conclusions. Pregnant wo men with a history of increased risk factors for PE and a decrease in the intensity of blood flow in the spiral arteries of the uterus at 18-20 weeks of gestation have a pronounced imbalance of the T-cell subpopulation, which is accompanied by a decrease in the production of T-helpers (CD4+) and an increase in the synthesis of T-suppressors/killers (CD8+), which causes a decrease in the immunoregulatory index. This is accompanied by the development of a cytokine imbalance with a predominance of pro-inflammatory cytokines and a deficiency of anti-inflammatory cytokines, and is also associated with a significant decrease in the concentration of IgG and a decrease in the number of B cells. Such changes are a consequence of the exhaustion of the reactivity of the humoral link of the general immunity, creating the conditions for the frequent manifestation of PE, which occurs in almost half of such women. The application of our proposed improved method of secondary prevention of pulmonary embolism in pregnant women with a high risk of developing this disease leads to significant positive changes in the work of the immune system and a corresponding improvement in clinical results. It makes it possible to reduce the frequency of PE development by 1.4 times and to prevent the occurrence of its severe forms by 2.6 times. [ABSTRACT FROM AUTHOR]

A multidisciplinary approach to microbiological implications of indoor air is fruitful for research as well as management of health and building problems. The Finnish and the Danish mold programs are examples of such productive collaborative studies. Dust samples taken from classrooms in schools where occupants complain of building-related symptoms (BRS) demonstrated an inflammatory potential in vitro, measured as a release of cytokine interleukin (IL)-8. An increase of the metabolite NO and liberation of tumor necrosis factor (TNF)-α and other cytokines during exposure were obtained in vivo, was presented based on these programs and on epidemiological studies on residential fungal contamination and health conducted in Canada and The Netherlands, New methods for assessing fungal exposure are PCA analysis for the toxigenic mold Stachybotrys chartarum and EPS-Asp/Pen for detecting of Aspergillus and Penicillium in dust. Based on a limited data set it is shown that emission rates of fungal spores are inversely proportional to relative humidity (RH), directly related to flow rate and to surface loading. Poor maintenance, risk constructions and risk materials are described in several studies as the main causes of water damage in buildings. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of blood glucose can damage multiple organs, including the brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities of diabetes. Despite the largely consistent link between diabetes and dementia, the underlying causes of neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders is neuroinflammation, a complex inflammatory process in the central nervous system for the most part orchestrated by microglial cells, the main representatives of the immune system in the brain. In this context, our research question aimed to understand how diabetes affects brain and/or retinal microglia physiology. We conducted a systematic search in PubMed and Web of Science to identify research items addressing the effects of diabetes on microglial phenotypic modulation, including critical neuroinflammatory mediators and their pathways. The literature search yielded 1327 records, including 18 patents. Based on the title and abstracts, 830 papers were screened from which 250 primary research papers met the eligibility criteria (original research articles with patients or with a strict diabetes model without comorbidities, that included direct data about microglia in the brain or retina), and 17 additional research papers were included through forward and backward citations, resulting in a total of 267 primary research articles included in the scoping systematic review. We reviewed all primary publications investigating the effects of diabetes and/or its main pathophysiological traits on microglia, including in vitro studies, preclinical models of diabetes and clinical studies on diabetic patients. Although a strict classification of microglia remains elusive given their capacity to adapt to the environment and their morphological, ultrastructural and molecular dynamism, diabetes modulates microglial phenotypic states, triggering specific responses that include upregulation of activity markers (such as Iba1, CD11b, CD68, MHC-II and F4/80), morphological shift to amoeboid shape, secretion of a wide variety of cytokines and chemokines, metabolic reprogramming and generalized increase of oxidative stress. Pathways commonly activated by diabetes-related conditions include NF-κB, NLRP3 inflammasome, fractalkine/CX3CR1, MAPKs, AGEs/RAGE and Akt/mTOR. Altogether, the detailed portrait of complex interactions between diabetes and microglia physiology presented here can be regarded as an important starting point for future research focused on the microglia–metabolism interface. [ABSTRACT FROM AUTHOR]

Introduction and aims: There is emerging evidence that heavy long‐term alcohol consumption may alter the neuroimmune profile. We conducted a meta‐analysis of the association between alcohol use disorder (AUD) and the extent of neuroinflammation using cerebrospinal (CSF), PET (Positron Emission Tomography), and postmortem studies. Design and methods: A comprehensive search of electronic databases was conducted using the Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols (PRISMA‐P) for AUD‐related terms in combination with neuroinflammatory markers and cytokine‐ and chemokine‐related terms for CSF, PET, and postmortem studies. Participants had to meet established criteria for AUD and/or heavy alcohol consumption with dependence features and be compared with healthy controls. Papers retrieved were assessed for inclusion criteria and a critical appraisal was completed using the Newcastle‐Ottawa Scale. A meta‐analysis was conducted on postmortem and PET studies. Results: Eleven papers met the inclusion criteria with CSF, PET, and postmortem studies included in the final analysis. Postmortem studies demonstrate significant heterogeneity (푄 (14) = 62.02, 푝 < 0.001), with the alcohol group showing higher levels of neuroimmune markers than controls (푑 = 1.50 [95% CI 0.56, 2.45]). PET studies demonstrated a lower [11C] PBR28 total volume of distribution (VT) for translocator protein in the hippocampus (g = −1.95 [95% CI −2.72, −1.18], p < 0.001) of the alcohol group compared to controls. Conclusion: There is emerging evidence across multiple diagnostic modalities that alcohol impacts neuroimmune signaling in the human brain. [ABSTRACT FROM AUTHOR]

The cytokine storm plays an indispensable role in the severe and critical illness and death of the COVID-19 vulnerable population. Thus, suppressing the cytokine storm is of great significance. Ginseng is a traditional Chinese herb originally used for improving physiological conditions and ameliorating disease. Common throughout the history of ancient Chinese medicine is utilizing ginseng as a major ingredient to successfully fight various pandemics, and the most famous decoction is Renshen Baidu powder. In recent years, ginseng has been observed to provide preventive and therapeutic benefits in the treatment of various conditions by suppressing hyper-inflammation, inhibiting virus intrusion, and balancing the host's immunity. This paper summarizes the ancient Chinese medicine books' recordings of, the clinical practice of, and the laboratory exploration of ginseng for the treatment of pandemics and COVID-19. Ginseng and its active ingredients were found to downregulate inflammatory cytokines, upregulate anti-inflammatory cytokines, stimulate the secretion of the antiviral cytokine IFN- γ , prevent viral entry and replication, and improve viral clearance. Furthermore, ginseng modulates both natural and acquired immunity during viral infection. Collectively, we propose that ginseng can act as a key immune response modulator against the cytokine storm of COVID-19. This paper may provide a new approach to discover specific medications using ginseng to combat COVID-19. [ABSTRACT FROM AUTHOR]

Time course studies revealed that the combination of Flt-3 ligand (FL), Steel factor (SF) and interleukin-3 (IL-3) did not elicit as large an amplification of the long-term culture-initiating cell (LTC-IC) population in serum-free cultures of CD34+CD38- cord blood (CB) cells as was obtained in similar cultures of adult human CD34+CD38- bone marrow (BM) cells (4- v 90-fold maximum increases), even though both total and colony-forming cell (CFC) numbers initially increased more rapidly in CB cultures. Multifactorial analysis of the short-term (10 d) effects of different cytokines identified FL and IL-6 in combination with the soluble IL-6 receptor (sIL-6R) as most important for expanding the CB LTC-IC population. In contrast, their counterparts in adult BM were most effectively stimulated by FL, SF and IL-3. For rapid generation of increased numbers of CFC, SF with either FL or IL-6/sIL-6R were found to be the most important contributors in cultures of CD34+CD38- CB cells, whereas, in analogous BM cultures, IL-6/sIL-6R and TPO (in addition to FL, SF and IL-3) were required. These findings reinforce the principle of altered cytokine responsiveness as a hallmark of early haemopoietic cell differentiation and demonstrate how cytokine requirements may change during human ontogeny. Identification of conditions for optimizing the expansion of different subsets of primitive CB cells has additional important implications for clinical transplantation and gene transfer. [ABSTRACT FROM AUTHOR]

Background: Burnout is increasingly being recognized as a contributory factor to the erosion of a positive psychological state. Studies have examined the relationship between burnout and various inflammatory markers such as IL-1, IL-6, and TNF-alpha. Burnout is also associated with increased systemic inflammation along a continuum of symptom severity. This protocol is for a scoping review looking at the link between burnout, inflammatory markers, and cardiovascular risks or diseases. Methods: This study will be based on the preferred reporting items for systematic reviews and meta-analyses guidelines/checklists and the report of the review will be based on the same guideline. The study seeks to address the following principal questions. (i) What are the relevant inflammatory biomarkers that mediate cardiovascular risk factors in burnout? (ii) How do inflammatory biomarkers mediate cardiovascular risk factors in burnout? The outputs obtained from the literature search will be deduplicated using the Rayyan software. Results: We would create table summaries of findings to inform a narrative synthesis of the evidence from the papers included. Conclusion: The review article would help to concisely synthesize the available evidence on the relationship between burnout, inflammatory markers, and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Macrophages are immune cells with high plasticity that are widely distributed in all tissues and organs of the body. Under the influence of the immune microenvironment of breast tumors, macrophages differentiate into various germline lineages. They exert pro-tumor or tumor-suppressive effects by secreting various cytokines. Pyroptosis is mediated by Gasdermin family proteins, which form holes in cell membranes and cause a violent inflammatory response and cell death. This is an important way for the body to fight off infections. Tumor cell pyroptosis can activate anti-tumor immunity and inhibit tumor growth. At the same time, it releases inflammatory mediators and recruits tumor-associated macrophages (TAMs) for accumulation. Macrophages act as "mediators" of cytokine interactions and indirectly influence the pyroptosis pathway. This paper describes the mechanism of action on the part of TAM in affecting the pyroptosis process of breast tumor cells, as well as its key role in the tumor microenvironment. Additionally, it provides the basis for in-depth research on how to use immune cells to affect breast tumors and guide anti-tumor trends, with important implications for the prevention and treatment of breast tumors. Bdt29Nrj2-xDAhjkrKeCKy Video Abstract [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor- α , and IFN- γ , as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor- β , and tumor necrosis factor- β. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors. [ABSTRACT FROM AUTHOR]

The heart is an organ with a limited capacity for regeneration and repair. In this paper, a new mathematical model is presented to study the left ventricular remodeling after myocardial infarction (MI) and followed stem cell therapeutic effort. The model represents the post-MI regeneration process of cardiomyocytes under stem cell therapy with oxygen restoration. The resulting system of nonlinear ordinary differential equations (ODE) is studied numerically in order to demonstrate the functionality and performance of the new model. The optimal time of stem cell injection for various oxygen restorations is determined. Moreover, the regeneration of cardiomyocytes is successfully correlated with improved left ventricle function observed in experiments. The proposed nonlinear ODE model is able to capture the complicated biological interactions in post-MI remodeling and can serve as a platform for in silico simulation and perturbation to optimize MI stem cell therapy. [ABSTRACT FROM AUTHOR]

The authors of this letter express gratitude for the interest and comments on their paper regarding cytokine production during cataract surgery. They agree that understanding the sources of cytokines and minimizing them is crucial for safer surgical outcomes. While the paper did not explore the sources of cytokines, the impact of these inflammatory cytokines on tissue effects, such as macular edema and inflammation, is of clinical significance. The authors suggest future studies to investigate the release of cytokines from different tissues using laboratory-based models of cataract surgery. They also raise the question of the impact of cytokines released from lens epithelial cells in their dataset, particularly in femtosecond-laser-assisted cataract surgery. [Extracted from the article]

The incidence of liver cancer is increasing year by year, and how to effectively diagnose early-stage liver cancer and improve the survival rate of liver cancer patients has become one of the current research topics of concern. Aiming at this problem, it is of great significance for the diagnosis of early liver cancer. With the in-depth research on the diagnosis of early-stage liver cancer, the research on growth differentiation factor 15 is gradually carried out, and its performance advantages are of great significance to solve the problem of detection and diagnosis of early-stage liver cancer. This study can improve the accuracy of early diagnosis of liver cancer. The purpose of this paper is to study the application of data mining in the study of clinical value of growth and differentiation factor 15 detection and diagnosis of early liver cancer. In this paper, the data mining algorithm is analyzed, the performance of the algorithm is experimentally analyzed, and the relevant theoretical formulas are used to explain. The results showed that the expression level of GDF-15 was significant in early primary liver cancer (tumor diameter <2.5 cm). Different from normal liver tissue (P < 0.01), there was a significant difference (P < 0.01) compared with adjacent tissue (P < 0.01). Serum GDF-15 can be used as a tumor marker for predicting early stage liver cancer. The high expression of GDF-15 in early stage liver cancer is an independent risk factor affecting the prognosis of liver cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, extracellular matrix (ECM), and soluble molecules forming the widely recognized tumor microenvironment. The main components of the tumor microenvironment include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), ECM, and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). The tumor microenvironment has been suggested to play a central role in tumor progression and treatment resistance. Accumulated evidence indicates that tumor maintenance, progression, and treatment resistance are determined by components of the microenvironment. Thus, targeting the components of the tumor microenvironment may have a therapeutic impact on melanoma treatment. The main topic of this paper deals with the main components of the tumor microenvironment and their impact as therapeutic targets in melanoma treatment. The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment. In the present review, we focus on the role of the tumor microenvironment components in the modulation of tumor progression and treatment resistance as well as the impact of the tumor microenvironment as a therapeutic target in melanoma. [ABSTRACT FROM AUTHOR]