immunity

The use of cryoablation for colorectal liver metastases (CLM) remains limited and controversial. This study aimed to investigate the antitumor immune response following cryoablation combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment in a CLM mouse model.

A CLM mouse model was established using BALB/c mice. The tumor-bearing mice were randomly divided into Control group, GM-CSF group, cryoablation group, and cryoablation + GM-CSF group. Tumor size, survival time, dendritic cells (DCs) count, serum cytokine levels (IL-4, IFN-γ), and the Th1/Th2 ratio (IFN-γ/IL-4) were compared among the four groups.

The combination of cryoablation and GM-CSF demonstrated synergistic effects, resulting in the smallest tumor lesion, longest mean survival time, and highest DC count on day 21 post-treatment compared to other groups. Both cryoablation alone and combined with GM-CSF significantly increased serum IFN-γ levels and suppressed IL-4 levels on day 21 compared to pre-treatment levels (P<0.05). Notably, the combination of cryoablation and GM-CSF significantly elevated the Th1/Th2 ratio (P<0.05).

Combining cryoablation with GM-CSF treatment holds promise for CLM management. It exhibits increased DC infiltration within the tumor microenvironment, enhanced immune responses, and prolonged survival in tumor-bearing mice.

Currently, the novel coronavirus disease (COVID-19) is one of the global challenges that remains inadequately addressed and is not being treated effectively. It is essential to acknowledge the role of supplements in strengthening the immune system to reduce the risk of infection. Food provides a well-established source of adequate macronutrients and micronutrients, all essential for the proper functioning of the immune system. Among the micronutrients, vitamins A, C, D, E, and B play crucial roles in the immune system's effective response to infections. This study explores the role of vitamins in the immune system and their impact on defense against COVID-19.

High-altitude environments pose challenges for broiler chickens, causing hypoxia, reduced growth rates, and increased disease susceptibility. This stress affects their cardiovascular and respiratory systems. This study explores the impact of L-carnitine and emulsifiers on lipid peroxidation, nitrite production (as an indicator of nitric oxide), and the heterophil/lymphocyte ratio in chickens experiencing high-altitude stress. Broiler chicks were raised at high altitudes (2100 m) for 42 days, divided into a control and three treatment groups receiving L-carnitine, emulsifier, or both. Blood samples were collected to analyze nitrite and malondialdehyde (MDA) levels. The heterophil/lymphocyte (H/L) ratio was determined from blood smears Nitrite levels were increased in the L-carnitine and L-carnitine + emulsifier groups compared to controls, while MDA levels decreased in both treatment groups compared to controls (P<0.05). Additionally, the H/L ratio was significantly reduced in all treatment groups compared to the control group (P<0.05). This study determined the significant benefits of L-carnitine and emulsifiers in improving the adverse effects of high-altitude conditions such as oxidative stress, vasoconstriction, and hypertension in broiler chickens.

Healthcare workers (HCWs) have faced challenging situations globally with increased stress and its related inflammatory/immune disorders, leaving behind a deficit in the number of HCWs worldwide. An increased focus on their physical and mental well-being is strongly warranted. Relaxation techniques such as yoga, pranayama, and meditation have great potential to promote health and prevent diseases. This study aims to determine the effects of Sudarshan Kriya Yoga (SKY) on inflammatory and immune parameters among HCWs. This pilot randomized controlled trial includes recruiting HCWs from a single centre in South India in 2022. We excluded any form of medical illness and recruited regular volunteers. The SKY intervention was delivered and followed up for 12 weeks. Baseline and post-SKY intervention blood investigations were compared between study and control groups (1:1 ratio) and analyzed. Thirty-eight subjects were recruited for the pilot study. Among them, 27 were females (71%) and 11 males (29%). Pro-inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein and neutrophil-to-lymphocyte ratio showed a decrease in mean values after 12 weeks in both groups, which was not statistically significant. A slight increase in interleukin (IL)-6 values and a higher IL-4 mean values was observed in the study group compared to controls. CD56 and CD8 counts were higher in the study group compared to controls. However, no such difference was noted in cortisol levels. This pilot study provides data for further large-scale studies to examine the effect of easily deliverable mindfulness-based interventions among the healthcare community to improve their health and well-being.

 Brucellosis in livestock and its transmission to humans through the consumption of contaminated dairy products is an important issue. The introduction of new approaches using immunogenic proteins against and diagnosing brucellosis is a serious issue in human health.

 Brucella abortus contains five proteins including: MOXR family ATPase-α2, T9SS C-terminal target domain-containing protein, Cobyric acid synthase, Hypothetical protein, and VirB11 type IV Secretion protein, which were considered and the designed recombinant polypeptide was produced and evaluated. The pure recombinant protein ABOR with 549aa in combination with chitin as an adjuvant was injected subcutaneously into guinea pigs to evaluate their immunity responses.

 The results indicated that the ABOR recombinant protein induced Th1 immunity with high levels of specific IgG (IgG2a) as well as Interferon-γ (IFN-γ), Interleukin-2 (IL-2), IL-12, and Tumor Necrosis Factor-alpha (TNF-α), compared to the control group. Th1/Th2 ratio analysis demonstrated the efficacy of ABOR protein combined with chitin in stimulating cellular immunity in the animals.

 Designed recombinant polypeptide combined with chitin showed ability for induction of cellular and humoral immunity an guinea pigs compared to RB51 vaccine.

Diffuse large B-cell lymphoma (DLBCL) is globally recognized as the most prevalent and aggressive subtype of non-Hodgkin lymphoma. While conventional treatments are effective initially, the disease can become resistant or relapse over time. The study aimed to examine the differentially expressed genes at the transcriptome level and molecular pathways in DLBCL patients.  This investigation utilized RNA sequencing analysis to compare differentially expressed gene samples from five diffuse large B-cell lymphoma patients with two healthy volunteers. These participants were admitted to UKM Medical Center, Kuala Lumpur between 2019 and 2020. The differentially expressed genes were conducted using the DESeq2 R package (version 1.10.1) using a negative binomial distribution model. The obtained P values were corrected with the Benjamin and Hochberg method and identified using a False Discovery Rate threshold of <0.05, with log2 fold change (FC) of ≥2 or ≤-2.  Results showed 73 differentially expressed genes between the two groups, among which 70 genes were downregulated, and three genes were upregulated. The differentially expressed genes analyzed with the Reactome pathway were significantly associated with the downregulation of antimicrobial humoral response (P<0.001), neutrophil degranulation (P<0.001), chemokine receptors bind chemokines (P=0.028), defensins (P=0.028) and metabolism of angiotensinogen (P=0.040).  These findings suggest that the identified pathways may contribute to cancer progression and weaken the immune response in diffuse large B-cell lymphoma patients. This study offers fresh insights into previously undiscovered downstream targets and pathways modulated by diffuse large B-cell lymphoma.

The objective of this study was to examine the impact of synchronous low-dose splenic irradiation (LDSR) on immune function in patients with esophageal cancer undergoing radiotherapy.

Twenty-one patients who were diagnosed with esophageal cancer were randomly allocated to either the control or experimental groups. The control group received routine radiotherapy alone, whereas the experimental group underwent simultaneous LDSR during radiotherapy. Low dosage radiation refers to a beam with a low linear energy transfer (LET) that delivers a dose of 0.2 Gy or less, or a high LET beam that delivers a dose of 0.05 Gy or less, while maintaining an exposure dose rate of 0.005 cGy/min. The lymphocyte subsets in the two groups were analyzed using flow cytometry at various time points during and after treatment. Additionally, complications and their occurrence times were recorded simultaneously.

Gradual decreases were observed in CD16+CD56+, CD3+CD4+, and CD4+/CD8+ ratios following radiotherapy in the control group (p < 0.05). However, no considerable differences were observed between the experimental groups in these ratios (p > 0.05). LDSR was found to induce immunological enhancement and counteract immune suppression caused by radiotherapy. Furthermore, the experimental group experienced larger cumulative dosages that led to problems compared to the control group, with a delayed onset. Despite receiving a higher cumulative dose, the experimental group exhibited lower levels of myelosuppression and radiation esophagitis than the control group (p < 0.05). Overall, the results suggest that synchronous LDSR can enhance immune function during radiotherapy in patients with esophageal cancer and reduce the adverse effects associated with routine radiotherapy.

Synchronous LDSR may induce immunological enhancement during radiotherapy in patients with esophageal cancer, reduce adverse reactions to routine radiotherapy, and enhance tolerance.

Brucellosis vaccines are designed to induce cellular immunity. An effective brucellosis vaccine could induce both cellular and humoral immunity. Serum Bactericidal Assay (SBA) is an important method for determining vaccine humoral immunity. This study is the first to observe humoral immunity in brucellosis by SBA.

Extracted Brucella abortus (B. abortus) Lipopolysaccharide (LPS) and Outer Membrane Proteins (OMPs) were injected into rabbits. Group 1 was injected with 25 µg of LPS, Group 2 was injected with 50 µg of OMPs, and Group 3 was injected with 1 ml of combined vaccine, 3 times every 2 weeks. The groups were challenged with B. abortus 544 in the second injection. Sera were separated 2 weeks after the last injection. SBA was performed, and each well was streak-cultured into a plate of Brucella agar. A colony count was done for each plate.

Results have shown, the third injection of the combined vaccine had the highest titer of 1/64, and the efficacy of the vaccine was 87.71%.

As a conclusion, the results of this study showed that LPS and OMP's from B. abortus can provide acceptable immunity.

Since the use of antibiotic growth promoters (AGP) have been banned in many countries, there is an urgent need to find a suitable alternative for them. Meanwhile, in recent years, special attention has been paid to herbal compounds. The present study was carried out to evaluate the effects of oregano (Origanum vulgare L.) as an alternative for AGPs on growth performance, carcass characteristics, and immune responses in broiler chickens.

Experimental: 

A total of 192 one-d-old female broiler chicks (Ross 308) were weighted and randomly allotted to 16 cages (12 chicks/cage). The dietary treatments were as follows: basal diet as a control, control + 4.5 mg flavophospholipol/kg, or control + 5 or 10 g oregano leaves powder/kg of diet.

Final body weight of broilers were not significantly affected by the dietary treatments, although it tended to increase in broilers fed diets containing antibiotic or 10 g oregano/kg of diet (P>0.05). Daily feed intake and feed conversion ratio (FCR) of broilers were not significantly affected by the dietary treatments; although during the whole experiment (0-42 d) FCR tended to improve in broilers fed diets containing antibiotic or 10 g oregano/kg of diet (P>0.05). The antibody titers against Newcastle disease virus (NDV) were significantly higher in broilers fed diets containing 5 g oregano/kg of diet (P<0.05).

Recommended applications/industries:

 In conclusion, the results indicate that supplementation of broiler diet with 5 g oregano/kg could enhance antibody titers against NDV without adverse effects on performance criteria.

CD8+ T cells play a crucial role in immune responses, and have significant potential in tumor immunotherapy. The JAK/STAT pathway is essential for cytokine signal transduction and is linked to immune escape. However, its role in mediating CD8+ T cell anti-tumor immunity in renal cancer is not fully understood. To study the mechanisms underlying CD8+ T cell-mediated anti-tumor immunity and propose new possibilities for immunotherapy in patients with renal cancer. CD8+ T cells from mouse spleens were sorted using immunomagnetic beads, and their purity was confirmed by flow cytometry. Proliferation was analyzed using CCK-8 and CFSE assays. Activation of CD8+ T cells was assessed through ELISA and Western blotting. The malignant properties of Renca cells were evaluated through flow cytometry, Calcein-AM/PI staining, wound healing, Transwell, Western blot, and immunofluorescence. A subcutaneous tumor model in nude mice was used to examine the role of JAK1/STAT1 pathway in vivo. Inhibitors of JAK1 and STAT1 significantly reduced the proliferation and activation of CD8+ T cell. Co-culture with CD8+ T cells increased apoptosis and inhibited the proliferation, migration, and invasion of Renca cells. The effects were diminished by JAK1 and STAT1 inhibitors, confirming that CD8+ T cells exert antitumor effects through the JAK1/STAT1 pathway. In vivo, inhibition of this pathway reduced the anti-tumor effects of CD8+ T cells. Inhibitors of JAK1 and STAT1 weakened the antitumor effects of CD8+ T cells, suggesting that targeting this pathway could enhance CD8+ T cell-mediated immunity in renal cancer.

After the influenza pandemic since 1918, the world is experiencing another viral challenge by a coronavirus (SARS-CoV-2). One of the most important strategies is to enhance the immune system.

Having an optimal nutritional behavior, following a balanced dietary pattern is essential for immune enhancement and reduce the risk of infectivity. Cytokine release syndrome (CRS) is hypothesized as one of the main causes of inflammation and consequently, lung damage in this viral infection. Undernutrition or overnutrition as the result of nutritional status can affect the immune system. Multivitamin and Minerals (MVM) intake can be beneficial in vulnerable populations such as the elderly, having a regular diet with the priority of healthy food portions can supply all daily requirements.

According to the WHO recommendations for consumption of fresh fruits and vegetables and also diets which have been hypothesized as an immune enhancer, the Mediterranean diet may involve all nutrients needed for improvement of the immune system.

Assessment of rubella immunity coverage relies on regular updates. This study aimed to determine the age-specific seropositivity rates among a large cohort of pregnant women approximately 12 years after vaccine introduction in Tunisia, where serosurveys are both old and scarce.

A prospective cohort study was conducted on pregnant women referring to the Maternity and Neonatology Center of Tunis in 2017. Eligible and consenting participants underwent blood sampling twice with a 15-day interval to detect and measure rubella-specific IgG and IgM antibodies. Demographic and obstetric data were also gathered.

A total of 800 participants with a mean age of 30.6±5 years (range: 17-48) were enrolled in this study. The overall seropositivity rate was 90.4% (n=723) (95%CI: 88.3-92.4). Also, 77 (9.6%) (95%CI: 7.6-11.7) participants were seronegative, among them 36 cases were in the first trimester of their pregnancy. The WHO minimum rubella immunization threshold of 95% was achieved for the first time in the 12-year-old vaccination program target population (96%) (95%CI: 92-99.8). No significant association was found between seropositivity rates and age, geographic origin, occupation, gestational age at the time of enrollment, parity, and abortion history (p> .05), but a significant association was found with educational levels.

Pregnant women vaccinated at the age of 12 showed a high immunization rate. Next decades would witness the elimination of rubella virus circulation as well as congenital rubella syndrome.

Lipoarabinomannan is one of the components of the significant structural cell surfaces of my- cobacteria and serves as an immunostimulatory factor. TNF-α and IL-12 are two examples of the anti-bacterial inflammatory cytokines that are activated and induced during infection.

In this study, mannan was extracted and processed, and then Bulb/c female mice were used in three groups, one group was given BCG vaccine, the other group was given BCG vaccine with mannan adjuvant, and a non-injected group was used as a control group. Inflammatory factors interleukin-12, TNF-α, IgG and IgM were measured in mouse serum.

The levels of the inflammatory factors interleukin-12 and TNF-α in the serum isolated from mice receiving the BCG vaccine with mannan adjuvant showed a significant difference compared to the group that received only the BCG vaccine and the control group [IL-12] and , with P≤0.05.The examination of the level of IgG immune factors in these three groups revealed a significant difference. The group that received the BCG vaccine with mannan adjuvant showed a marked contrast compared to the group that received only the BCG vaccine and the control group, with P≤0.05. The level of IgM was higher in the group that received the BCG vaccine alone compared to the adjuvant vaccine group and the control group, with P≤0.05.

Our results indicated that mice receiving the BCG vaccine with mannan adjuvant had significantly higher serum levels of IL-12, TNF-α, and IgG than the group receiving BCG alone.

Dear Editor, In addition to the well‑known pox infections, new zoonotic pox diseases have emerged, and they are now a global concern. Monkey pox has expanded across Europe as a result of its widespread outbreak, posing a severe public health risk. Monkey pox is an uncommon pox infection that has resurfaced due to zoonosis.

Food additives are substances that have long been applied in processed foods, either natural or synthetic. Several purposes have been fulfilled by the application of food additives, the two most notable of which are known to be preventing food spoilage and providing specific colors and flavors. Some food additives are added to food products through direct contact, whereas the rest are added indirectly e.g., through their packaging bags. In addition to the economic and commercial benefits provided by food additives, over the past two decades, studies have demonstrated a significant correlation between excessive consumption of the foods containing such additives (e.g., BHA and BHT) and several adverse health effects, e.g., the incidence of cancer and skin conditions, among others. Through different age groups, children have been found to be the population at the highest risk for such adverse effects induced by food additives. Indeed, it has been reported that food additives may give rise to attention deficit hyperactivity disorder (ADHD) among the child population. Emerging evidence has shown that emulsifiers (e.g., carboxymethyl cellulose and polysorbate), employed as food additives, might alter gut microbiota composition, leading to ulcerative colitis, affecting immune and inflammatory responses, and mental health problems. Therefore, in this review, alongside the beneficial impact of food additives, their adverse health effects as well as their acceptable daily intake have been investigated.

Nephrotic syndrome (NS) is the most common pediatric renal disease. Immune dysregulation, prolonged immunosuppressive treatment, and recurrent prolonged proteinuria in NS cause alterations in serum immunoglobulins, especially hypogammaglobulinemia. Thus, anti-HBs titer may be reduced in NS patients. We assessed anti-HBs titer among hepatitis B-vaccinated children with NS.

This case-control study was conducted at the Department of Paediatrics of the Institute of Child & Mother Health, Dhaka, from July 2020 to June 2021. Sixty-one children with primary and recurrent NS previously vaccinated according to the expanded programme on immunization program were evaluated for anti-HBs titer and compared with 61 age- and sex-matched healthy children.

Protective anti-HBs titer was found in 29(47.5%) and 40(65.6%) cases in the case and control groups, respectively. The mean anti-HBs titer was 37.2±35.5 IU/L in the case group and 55.7±28.3 IU/L in the control group, which showed a significant difference between the groups. The mean anti-HBs titer was 52.9±35.5 IU/L in the first attack, 33.9±36.8 IU/L in the infrequent relapse nephrotic syndrome (IFRNS), and 22.2±27.41 IU/L in the frequent relapse nephrotic syndrome (FRNS), respectively. The difference was also significant statistically. The mean anti-HBs titer was lower in the FRNS and IFRNS and significant in the FRNS compared to the first attack. The mean anti-HBs titer was significantly (P<0.05) lower in the IFRNS and FRNS compared to the controls.

Anti-HBs titer was found significantly lower than the protective level in the first attack and relapse cases of NS.

The globe is currently dealing with one of the worst epidemics, SARS-CoV-2. The various drugs can treat the clinical symptoms of SARS-CoV-2, and combination therapies may be more effective than monotherapy. This study discussed various COVID-19 subtypes, pharmaceutical effectiveness, the advantages and disadvantages of medications, and mortality rates in various countries. The drugs were reviewed as well. The macrolides family can produce anti-inflammatory cytokines against COVID-19, but they may cause side effects such as bacterial resistance. Although antimalarial drugs may inhibit the entrance of the virus into cells, they are not a common medicine in COVID-19 treatment. The simultaneous consumption of corticosteroids with other drugs can be beneficial for high-intensity patients. In addition, remdesivir may be effective in severe cases of the disease. However, the administration of several drugs can be more effective compared to a single drug. Although pharmacological combinations can be effective in treating SARS-CoV-2, vaccines are considered to be the most successful approach for reducing COVID-19. Pfizer/ BioNTech and Moderna vaccines are based on the mRNA of viruses and provide an efficiency of about 95%. Sputnik V was prepared by two replication-incompetent adenovirus vectors. The AstraZeneca–Oxford vaccine was prepared based on viral vectors, and its efficacy has a variable range of 62%–90%. The vaccines based on an inactivated virus provided innate immunity in the body. Soberana 2 is a recombinant vaccine. Generally, all vaccines may have positive effects on the prevention of COVID-19, but further clinical trials are necessary. These findings suggest each available vaccine is advised for protection against COVID-19.

Immune cells and their secreted cytokines are known as the first barrier against pathogens. Leishmania major as an intracellular protozoan produces anti-inflammatory cytokines that lead to proliferation and survival of the parasite in the macrophages. miRNAs are small non-coding RNA molecules that regulate mRNAs expression. We aimed to investigate the relationship between the expression of TGF-β and a bioinformatically candidate miRNA, in leishmaniasis as a model of TGF-β overexpression.

The miRNAs that target TGF-β -3´UTR were predicted and scored by bioinformatic tools. After cloning of TGF-β-3'UTR in psi-CHECK TM- 2 vector, targeting validation was confirmed using Luciferase assay. After miRNA mimic transfection, the expression of miR-27a, TGF-β, as well as Nitric Oxide concentration was evaluated.

miR-27a received the highest score for targeting TGF-β in bioinformatic predictions. Luciferase assay confirmed that miR-27a is targeting TGF-β-3'UTR, since miR-27a transfection decreased the luciferase activity. After miRNA transfection, TGF-β expression and Nitric Oxide concentration were declined in L. major infected macrophages.

Bioinformatic prediction, luciferase assay, and miRNA transfection results showed that miR-27a targets TGF-β. Since miRNA and cytokine-base therapies are developing in infectious diseases, finding and validating miRNAs targeting regulatory cytokines can be a novel strategy for controlling and treating leishmaniasis.