Expression and location of nucleolin are often abnormal in malignancies, which may result in the production of autoantibodies. Despite this, the identification of such autoantibodies may be essential for the early diagnosis and prognosis of cancers.
In this investigation, the recombinant nucleolin protein was generated using an Escherichia coli expression system and was used an indirect enzyme-linked immunosorbent assay to detect anti-nucleolin autoantibodies in cancer patients' sera.
Lung cancer patients' autoantibodies displayed the highest seroreactivity with the recombinant protein, with area under the curve of 0.948 and sensitivity and specificity of 85% and 96.67%, respectively (accuracy=92%). Anti-nucleolin autoantibodies were linked with lung tumor size (r=0.793), tumor, node, metastasis staging (r=0.643), and proliferation (r=0.744).
These autoantibodies distinguished patients with early-stage lung cancer from healthy controls. Since anti-nucleolin autoantibodies are strongly linked to tumor size, clinical staging, and growth, they can be used to measure how well a treatment is working.  

Cell-based cancer therapies have led to a paradigm shift in the treatment of patients with various cancers. To date, a vast majority of cancer immunotherapies have used genetically engineered T cells to target tumors. Stimulation and ex vivo expansion of T cells, as one of the crucial starting materials for T cell manufacturing, have always been a critical part of adoptive T-cell therapy (ACT). Typically, anti-CD3 and anti-CD28 monoclonal antibodies (mAbs) along with interleukin-2 (IL-2), through transducing signals one, two, and three, respectively, are essential for in vitro T cell activation. Terminal differentiation and replicative senescence are the main barriers of the ACTs during the manufacturing of engineered T cells ex vivo.In
this study, we aimed to compare the T cell activation protocol that we  developed in our lab (soluble anti-CD3/28 mAbs) with a common T cell activation protocol (immobilized anti-CD3/soluble anti-CD28) in terms of T cell expansion, activation, immunophenotype, and cellular fate.
We observed that T cells were equally expanded in both protocols. Notably, our modified protocol promoted the outgrowth of CD8⁺ T cells postactivation. Concerning the low concentrations of both soluble anti-CD3 and anti-CD28, the modified protocol could significantly enrich memory T cell subsets.
In conclusion, our data demonstrated that the soluble CD3/28 mAbs protocol is cost-effective and more efficient for generating more potent T cells, thereby expecting a better therapeutic outcome.

Signal transducer and activator of transcription 3 (STAT3) has been introduced as one of the critical genetic factors in the pathogenesis of rheumatoid arthritis (RA). Single nucleotide polymorphisms (SNPs) in microRNA binding sites, known as miRSNPs, are a class of common variants in the 3′ untranslated regions of genes targeted by miRNAs. miRSNPs unbalance gene expression by disrupting the binding regions of microRNAs. In this study, we intended to evaluate the association of two miRSNPs with the risk of RA development and its clinical features.
We studied 120 Iranian patients with RA and 125 non-RA subjects as controls. The genotypes and alleles of rs1053005 and rs1053023 in each individual were assessed by the high-resolution melting method.
The distribution of STAT3 variants did not differ markedly in RA patients compared to healthy controls. Stratification analysis revealed that rs1053005 was linked with a higher concentration of C-reactive protein and an increased erythrocyte sedimentation rate, two indicators of inflammation and disease activity in RA patients. The rs1053023 variant was correlated with higher levels of creatinine as an indicator of renal involvement.
Our data demonstrate an association between STAT3 variants and clinical characteristics of RA, such as disease activity and probably kidney impairment.  However, we did not observe a significant relationship between the two targeted variants and a predisposition to RA.

 Natural killer (NK) cells play a role in the pathogenesis of rheumatoid arthritis (RA). Upregulated levels of programmed cell death protein 1 (PD-1) is a sign of exhausted NK cells that could be regulated by microRNAs (miRNAs). In this investigation, we determined PD‑1 expression on NK cells (as a representation of NK cell exhaustion) in RA patients and evaluated if miRNAs are involved in the modulation of PD-1 expression in NK cells.
Peripheral blood specimens were obtained from 40 RA patients and 20 healthy subjects. NK cells were isolated by negative selection from a pool of peripheral blood mononuclear cells. The frequency of PD-1–expressing NK cells and the expression of PD-1 on NK cells were analyzed by flow cytometry. Real-time PCR was used to measure the expression levels of PD-1 mRNA and miRNAs in the NK cells.
The percentage of the PD-1–expressing NK cells and Mean fluorescence intensity (MFI) of PD-1 expression on the NK cells were significantly higher in the RA cases compared to the controls. The mRNA expression of PD-1 was significantly upregulated in NK cells from RA patients compared to healthy subjects. The expression levels of miR-28, miR-138, and miR-4717 were significantly downregulated in the NK cells from RA patients compared to the healthy group.
In RA, miRNAs probably regulate the NK cell exhaustion process through driving PD-1 expression.

Placental extract (PE) and exosomes from pregnant mice appear to have immunomodulatory and neuroprotective effects. In this study, we assessed the potential therapeutic effects of PE and exosomes obtained from pregnant mice in experimental autoimmune encephalomyelitis (EAE) mouse models.
C57BL/6 mice, 8 to 12 weeks of age, were prepared and administered PE, exosomes, and glatiramer acetate (GA), as an FDA-approved treatment for multiple sclerosis (MS), after EAE induction. Thereafter, the therapeutic effects of treatment were evaluated by measuring the clinical courses of the mice as well as determining the number of regulatory T (Treg) cells using flow cytometry, cytokine levels, and microRNA-326 expression via real-time PCR.
GA, PE, and exosomes reduced clinical severity, the extent of spinal cord demyelination, and the infiltration of inflammatory cells into the spinal cord. The frequency of CD4⁺CD25⁺FoxP3⁺ Treg cells increased after treatment of EAE mice with GA, PE, and exosomes. The mRNA expression of the inflammatory cytokines (interleukin-17  and interferon-gamma), as well as miR-326 expression, decreased significantly in the EAE mice after treatment with GA and exosomes.
PE and exosomes from pregnant mice are involved in the modulation of Treg/Th17 balance and provide a therapeutic approach for MS. Further clinical studies will hopefully confirm the safety and efficacy of such treatments in MS patients.

Chronic lymphocytic leukemia (CLL) is the clonal expansion of mature CD5+ B cells and the most common lymphoproliferative disease in adults (B1-CLL). B1 cells' anti-inflammatory effects include the production of natural IgM (nIgM) by the spleen and bone marrow, decreased inflammatory cytokines as a primary response to maintaining tissue homeostasis, and enhanced release of transforming growth factor β (TGFβ).
We used the flow cytometry technique in peripheral blood from patients with CLL and multiple sclerosis (MS) to immunophenotype B cells and their subpopulations. Whole blood from CLL and MS patients, as well as healthy controls, was used to detect nIgM using the VH4-34 gene copy number and real-time RT-PCR.
We found that the proportion of CD5+ B cells was significantly lower in MS patients than in the control group and that CD5+ B lymphocytes were significantly higher in CLL patients than in the control group. Compared to the control group, CLL patients had significantly higher levels of the VH4-34 gene copy number. On the contrary, MS patients had significantly lower VH4-34 gene copy number levels compared to the control group.
As the number of antibodies in CLL patients increases due to the high number of B1 cells, we propose a new way to treat MS by extracting this natural antibody from the sera of CLL patients and injecting it into MS patients.

coronavirus disease of 2019 (COVID-19) can be complicated by acute respiratory distress syndrome (ARDS) and may be associated with cytokine storm and multiorgan failure. Anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for this purpose. In this study, we evaluated the immunomodulatory effect of mannuronic acid (M2000), which is a novel NSAID, on COVID-19-related cytokine storms.
This study was conducted in vitro on blood samples of 30 COVID-19 patients who presented with ARDS to a referral center. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. M2000 was administered with the dosages of 25 µg/well and 50 µg/well after 4 hours of incubation at 37°C. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess mRNA gene expression. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the supernatant PBMC levels of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ.
Both mRNA expression and the supernatant PBMC levels of IL-17, TNF-α, IL‑6, and IFN‑γ were decreased in PBMCs of COVID-19 patients treated with M2000 compared with the control  group.
For the first time, it was observed that M2000 could be effective in alleviating the inflammatory cascade of COVID-19 patients based on an in vitro model. After further studies in vitro and in animal models, M2000 could be considered a novel NSAID drug in COVID-19 patients.

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients.

In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1×  cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17).
UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8⁺ T cells. 
These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area. 

Allergic rhinitis (AR) is an allergic disease induced by the T helper 2 (T_H2) lymphocyte immune response, where its mediators are the primary cause of clinical symptoms. Environmental factors are the primary determinants of the allergic response in genetically susceptible individuals. This study investigates the effects of climate conditions (warm, cold, humid, and dry) on allergic rhinitis.
AR models were created in mice under 4 different conditions. We investigated AR-related behavior (sneezing and nose rubbing), as well as total immunoglobulin E (IgE), histamine, interleukin-4 (IL-4), leukotriene (LT) B4 and LTC4 levels, and gene expression of CysLT1R, HRH1, and MUC5a.
Nose rubbing, histamine levels, and the expression of MUC5a and HRH1 were increased in AR models in cold conditions, and sneezing was increased in AR models kept in dry conditions. LTB4 and LTC4 levels and the expression of CysLT1R in AR models kept in a wet environment also significantly increased compared with the control group. The levels of total IgE and IL-4 showed no significant changes.
Air temperature and humidity affect AR pathophysiology, and weather conditions can be essential in controlling AR.

There is an urgent need to discover novel prognostic biomarkers and treatment strategies for gastric cancer (GC) patients. Several immune-related markers have been proposed as prognostic tools and immunotherapeutic targets to manage diseases. In this regard, we evaluated the expression pattern and prognostic significance of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), CD45RO⁺ tumor-infiltrating lymphocytes (TILs), and DNA mismatch repair (MMR) proteins (MLH1, MSH2, PMS2, and MSH6) in non-metastatic intestinal-type gastric adenocarcinoma.
Samples and data from 70 GC patients were collected. Immunohistochemistry staining was used to detect the markers. We then evaluated the prognosis significance of each marker and their intercorrelation.
Cytoplasmic PD-1 expressed by tumor cells was significantly associated with poorer survival. However, multivariate analysis indicated stronger prognostic values for TNM stage, tumor location, and extracellular mucin. A significant positive association was found between CD45RO^high TILs and PD-1 expression on tumor-infiltrating cells (TICs). All GC patients with deficient MMR (d‑MMR) had a higher number of CD45RO⁺ TILs and were associated with PD-1⁺ TICs and PD‑L1⁺ tumor cells (TCs). However, the difference was not statistically significant.
Despite the association of PD‑1 overexpression on TCs with shorter overall survival, histopathological factors, including tumor location, TNM stage, and extracellular mucin, remain the most decisive prognostic factors in non-metastatic intestinal-type gastric adenocarcinoma. Additionally, our data support a prognostic role for d-MMR and CD45RO, but not PD-1 and PD-L1 expression on TICs.

The green-lipped mussel (Perna canaliculus) originates from New Zealand. To preserve the health benefits of green-lipped mussel meat, it is freeze-dried to make a long-lasting powder. The powder is used to treat arthritis because of its potential anti-inflammatory properties. The report describes a 54-year-old woman who developed immediate rhinoconjunctival and respiratory symptoms after inhaling green-lipped mussel powder she gave to her dog for arthritis.
A skin prick test with green-lipped mussel powder was performed. Protein extracts from P canaliculus were separated by sodium dodecyl–sulfate polyacrylamide (SDS) gel electrophoresis and probed with serum from patients and serum preincubated with green-lipped mussel extract. Bound immunoglobulin E (IgE) was detected by specific anti-human-IgE antibodies, and IgE-binding proteins were subsequently identified by liquid chromatography and mass spectrometry.
The skin prick test was positive for green-lipped mussel. Specific IgE against green-lipped mussel extract was detected using Western immunoblotting. These potential allergenic proteins were identified by mass spectrometry as actin, tropomyosin, and paramyosin.
All three allergens are reported for the first time for P canaliculus. Actin is a major allergen in Paphia textile, paramyosin in Sarcoptes scarbiei, and tropomyosin in Haliotis discus. For all IgE-binding proteins, the software AllCatPro predicted high allergenicity, supporting our conclusion that these proteins from P canaliculus may also be allergenic. The identification of allergens from P canaliculus provides the opportunity for specific tests to assess the frequency of allergic reactions to P canaliculus.

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