Serum Levels Of IL-6 Research Articles

Impact of Human IFITM3 Polymorphism rs12252 on COVID-19 Severity and Mortality in an Egyptian Cohort

Abstract Background Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease with a high mortality rate, caused by infection with severe acute respiratory syndrome coronavirus 2. Variants of the gene encoding the interferon-induced membrane protein IFITM3 have been linked to severe viral illnesses. We investigated whether the COVID-19 clinical outcomes caused by SARS-CoV-2 infection in a cohort of COVID-19 Egyptian patients were inconsistent and could have been caused by the IFITM3-SNP rs12252 polymorphism. Aim of the Work The purpose of this study is to determine the frequency of the IFITM3 rs12252 SNP in a cohort of COVID-19 Egyptian patients, and its impact on illness severity and outcome, as well as its influence on IL-6 serum levels. Patients and Methods This cross-sectional study included 100 patients diagnosed as positive for COVID-19. They were enrolled in AL-Obour Quarantine Hospital. They were categorized into three groups, mild cases, who attended AL-Obour outpatient clinic, moderate and severe cases who were admitted to the hospital ward and ICU, respectively. All subjects of this study were subjected to full medical history, clinical evaluation, laboratory investigations, serum IL-6 levels by ELISA and IFITM3 gene polymorphism by real-time PCR. Results The results of the current study demonstrated a significant difference between mortality and the minor G allele of rs12252 within IFITM3 in COVID-19 patients (OR = 4.5 [95% CI; 1.4–14.30], P = 0.006). IL-6 showed no association either to disease severity or IFITM3 rs12252 genotype frequency. Conclusion The present study has shown a significant association between G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results failed to demonstrate any significant association between rs12252 polymorphism and disease severity, ICU admission or serum IL-6 levels. Therefore, understanding the interaction between SARS-CoV-2 and the IFITM3-rs12252 allele could help identify novel therapeutic targets, leading to precise biological and immune therapy for SARS-CoV-2 infection.

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1β, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell’s median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1β, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

Serum levels of IL-6 and IL-10 on admission correlate with complications in elderly patients with hip fracture

ObjectivesAgeing may cause a progressive pro-inflammatory environment and alter functionality of different immune-cell populations. The aim of the present study is to examine the influence of certain serum immunological parameters on hospitalization stay and complications in patients who have suffered a hip fracture. Patients and methodsA prospective study was carried out with 87 patients (63 women) presenting with either trochanteric femoral fracture or Garden IV displaced subcapital fracture. The average age was 84.43 ± 9, ranging from 65 to 104 years old. Data regarding different comorbidities were recorded at the time of arrival. The morning after patient's admission peripheral blood samples were obtained and a series of immunological parameters were determined: leukocyte formula, platelets count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 levels, T-lymphocytes count, number of cells/mm3 and percentages of CD3, CD4, CD8, CD3-/CD16/56+ (NK cells), and CD3-/CD19+ (B cells). ResultsIL-6 serum levels presented a positive and significant correlation with higher levels of CRP (p < 0.001), IL-10 (p = 0.002), and higher percentages of NK CD56+ cells (p = 0.046). IL-6 serum levels at hospitalization presented a positive and significant correlation with a longer hospitalization stay (p = 0.037). Hospitalization increased by 0.231 days for every 1 pg/mL above the IL-6 mean value (40.43 pg/mL). Lower serum IL-10 levels on admission were associated with the appearance of symptomatic urinary tract infection during hospitalization (p = 0.032). Higher number of CD19+ cells/mm3 presented a significant relationship with pneumonia (p = 0.018) and symptomatic urinary tract infection (p = 0.0019). ConclusionsIL-6 serum levels on admission showed a positive and significant correlation with a longer hospitalization stay in elderly patients presenting with hip fracture. Lower levels of IL-10 in peripheral blood on admission were associated with symptomatic urinary tract infections. A higher number of CD19+ cells/mm³ was significantly associated with pneumonia and symptomatic urinary tract infection. These immunological variables on admission may serve as risk indicators of complications during hospitalization.

Estimation of IL-8 and TNF-α Levels in Pediatric Diarrhea Patients Infected with Enterohemorrhagic E. coli O157:H7

Abstract Background: Verotoxins are bacterial virulence factors produced by E. coli O157:H7, transmitted by the fecal-oral route. Objectives: The aim of this article was to diagnose E. coli O157:H7 which causes diarrhea and sometimes develops into HUS, which considers pig health problems and estimates the levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α in the sera of pediatric patients infected with Enterohemorrhagic E. coli compared to the control group. Materials and Methods: Stool and blood samples were collected from 421 pediatric patients with diarrhea, ranging in age from birth to 13 years old, from March to October 2022. Samples were collected from Al Noor Teaching Hospital, Babylon Hospital for Pediatric and Gynecology, Hilla, Iraq. E. coli O157:H7 was cultured on eosin methylene blue (EMB) and Sorbitol MacConkey agar (SMA), confirmed by biochemical test and cultured on HiCrome E. coli O157:H7 selective medium which was an agar base supplemented with cefixime tellurite agar. Serum from 30 pediatric diarrhea patients infected with E. coli O157:H7 compared with 30 healthy children as control group used to determine serum levels of IL-8 and TNF-α by sandwich ELISA. Results: The results revealed that out of the total 421 samples used in this study, E. coli O157H:7, represented 7% (30 of 421) stool samples. This 30serum samples of infected children as well as 30 samples from healthy children subjected to the estimate serum level of IL-8 and TNF-α which record significant differences P ≤ 0.01 and P ≤ 0.05 to this cytokines in different age group; the mean of IL-8 level was 283.62 ± 17.8 pg/mL (7–9 years), and the mean of TNF-α was 208.62 ± 28.7 pg/mL (10–13 years) comparative with the control group of 80.58 ± 15.4pg/mL and 32.50 ± 7.5 pg/mL, respectively, and also result showed an increased mean level of IL-8 than TNF-α in the male comparative with female 195.19 ± 10.4 pg/mL and 159.05 ± 12.4 pg/mL, respectively, comparative with the control group. The result showed no significant differences in IL-8 and TNF-α between watery diarrhea (192.43 ± 24.3 pg/mL and 136.05 ± 20.4 pg/mL) and bloody diarrhea (189.02 ± 22.5 pg/mL and 123.80 ± 13.5 pg/mL), and also result showed significant increase of mean sera level of IL-8 than TNF-α in formula feeding children comparative with breastfeeding children (187.87 ± 19.5 pg/mL and 119.93 ± 17.4 pg/mL, respectively). Conclusion: The finding of this study suggested that increased levels of IL-8 and TNF-α are present in all age groups, in male comparative with female, and also in pediatric diarrhea feeding by formula than breastfeeding and no differences of this cytokine according to consistency of diarrhea. These results contribute to using the immune profile as a serological marker for diagnosing diarrhea caused by E. coli O157:H7 in comparison with the control group.

Analysis of Th17 cell population and expression of microRNA and factors related to Th17 in patients with premature ovarian failure

Folliculogenesis is the process where follicles in the ovaries develop and eventually lead to ovulation. Any disruption to this process can cause premature ovarian failure. miR-326 is one of the microRNAs whose expression leads to Th17 production. Th17 activates the immune system to respond more vigorously, and by producing interlukins and cytokines causes inflammation and autoimmune disorders. Th17-induced inflammation and Th17/Treg imbalance can result in POF. This investigation took samples from 30 POF patients and 30 healthy people. The study utilized PCR to assess the expression levels of cytokines, specific transcription factor (ROR-γt), and miR-326. Additionally, ELISA was employed to analyze serum levels of IL-17, IL-21, IL-23. Furthermore, flow cytometry was utilized to determine the frequency of Th17. Compared to the control group, our results demonstrated a rise in the transcription factor RORɣt and a considerable rise in the frequency of Th17 cells in patients with POF. The level of inflammatory cytokines IL-17, IL-21, and IL-23 secreted in serum samples of patients with POF increased significantly compared to the control group. Results of investigating microRNA associated with Th17 cells also showed increased expression of miR-326 in females suffering from POF. The elevation of pro-inflammatory markers in women with POF contrary to the control group underscores the significant involvement of the immune system in pregnancy disorders pathogenesis. Consequently, immunological factors may serve as promising biomarkers for predicting POF likelihood in high-risk women in the future.

Evaluation Serum Levels of Resistin and Interleukins-6 as Predictors of Left Ventricular Remodelling in Patients with Acute ST Elevation Myocardial Infarction

Objectives: To identify some biochemical parameters that help predict LV remodelling after STEMI. By determining serum levels of Resisten and IL-6 in patients with ST-segment elevation MI (STEMI) and apparently healthy controls. Patients &amp; Methods: This prospective case-controlled study was conducted from beginning May 2023 to end of October 2023. This study was conducted on 110 individuals, including sixty-two patients (50 males and 12 females) who had undergone a STEMI and forty-eight healthy control subjects. The information about patients in this study was retrieved from patients' hospital records. The samples were collected from Azadi Teaching Hospital/ Kirkuk on patients with STEMI. Forty-eight of apparently healthy sex and age-matched controls were included in this study. The data were collected from the cases group as (G2) means: From the moment the patient arrives to internal resuscitation and up to 48 hours and at the baseline of the STEMI (ST elevation of the myocardial fraction), and (G3) means: After 4-6 months follow up, These states were also compared to the control group composed of (48) individuals who were apparently healthy. About five ml of blood was collected from the antecubital vein for both patients and healthy individuals in an anticoagulant tube to estimate the Resisten and IL-6 levels. Results: The results of the study showed that the serum level of resisten were significantly higher in group G2 (patients group) in comparison to those of the A1 (control group) P &lt;0.01. The current research demonstrated non-significant differences in IL-6 levels between (G1 and G2), while showing highly significant differences between A1 and A3; this was also applicable for G2 and G3. Conclusion: The current study concluded that there are significantly increasing of Resistin levels in patients in matching to control groups. Also, it was noticed that IL-6 mean concentration levels were lower in A2 in comparison to A1 but higher than in A3.

The Protective Role of IL-17 and IL-22 in COVID-19 Infection.

The development of a cytokine storm in Coronavirus Disease 2019 (COVID-19) infection can make the disease fatal. We hypothesize that this excessive cytokine production impairs mucosal healing. IL-17 and IL-22 are cytokines that play a key role in protecting and regenerating mucosal tissues.IL-17 and IL-22 support each other and the imbalance between them plays a role in the pathogenesis of many rheumatologic diseases. To investigate whether COVID-19 severity is related to IL17, IL-22, and the IL-17/IL-22 ratio. The study was planned prospectively and included 69 patients with active COVID-19 infection.Three groups were created: patients with upper respiratory tract infection, pneumonia, and cytokine storm. Blood samples were taken from the patients upon their first admission and serum levels of IL-17 and IL-22 were measured using the enzyme-linked immunosorbent assay (ELISA). We assessed the relationship between IL17, IL22, IL17/IL22 ratio, clinical and lung involvement by comparing them with the healthy group. The levels of IL-17 were significantly higher in COVID-19 patients with upper respiratory tract infection compared to the control group (p=0.027). IL17/IL-22 ratio significantly increased in patients with cytokine storm compared to the healthy controls (p=0.027). Serum levels of IL-22 were negatively correlated with the CO-RADS score (r=-0.31, p=0.004), while IL-17/IL-22 ratio was positively correlated with the CO-RADS score (r= 0.29, p=0.008). Levels of IL-17, IL-22 and IL-17/IL-22 may provide valuable insights into the progression of COVID-19.

Differential Pharmacodynamic Effects on Psoriatic Biomarkers by Guselkumab Versus Secukinumab Correlate with Long-Term Efficacy: An ECLIPSE Substudy

IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at ClinicalTrials.gov (NCT03090100).

Comparison of ozone therapy and routine medical treatment effect on disease severity and serum level changes of IL-33 in patients with remitting-relapsing multiple sclerosis: A parallelled randomised clinical trial

IntroductionIL-33 is an inflammatory cytokine involved in the pathogenesis of Multiple sclerosis (MS) as an autoimmune inflammatory disease. Ozone therapy has been shown to improve the symptoms of the disease in previous studies. Given the limitations of previous studies, we investigated the effect of adding ozone therapy to conventional medical treatment in remitting-relapsing multiple sclerosis (RR-MS) patients from the points of disease severity and blood levels of IL-33. MethodsThis clinical trial was performed on 66 RR-MS patients, among whom 55 finished the study. The patients were divided randomly into two groups; one group (intervention) received ozone therapy in addition to the routine medical treatment, and the other group (control) received only routine medical treatment. The level of IL-33 was measured by ELISA, and the severity of the disease was measured by an expanded disability status scale (EDSS) in all patients before and after the treatment. Finally, the relationship between the serum levels of IL-33 and EDSS score with the type of treatment was evaluated. The research project was registered at the International Center for the Registration of Clinical Trials in Iran (IRCT20171105037262N3). ResultsOur findings showed that the serum levels of IL-33 in the ozone plus medical-treated group significantly decreased compared to the medical-treated group (P<0.001). The EDSS score also decreased significantly in the ozone plus medical-treated group compared to the medical-treated group (P=0.019). ConclusionOzone therapy reduces the severity of RR-MS. Such an effect may be influenced by modifying IL-33 levels.

Colostrum supplementation enhance mental health status and alleviate pain in patients with acetabular fracture: A randomized, controlled, clinical trial

IntroductionRole of oral colostrum on mental health status, pain, and inflammatory markers in patients with acetabular fracture was investigated. Materials and MethodsFor 21 days, the intervention group received 40 g of colostrum daily and the control group received a placebo. Changes in mental health status, pain, and serum levels of CRP and IL-6 were evaluated over 90 days. ResultsThe risk of depressive symptoms and sleep disturbances in the colostrum group (n = 41) was significantly lower than the control group (n = 39), 14 and 60 days after surgery. The risk of anxiety symptoms in the colostrum group, 2 and 3 months after surgery, was significantly lower than the control group.Generalized estimating equation showed that the mean pain score and serum levels of CRP and IL-6 in the colostrum group were significantly lower than the control group during 90 days of follow-up. ConclusionColostrum improves mental health status, pain, and inflammatory markers.Iranian Registry of Clinical Trials: IRCT20220424054643N1.

Ginseng extract improves pancreatic islet injury and promotes β-cell regeneration in T2DM mice.

Panax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting β-cell regeneration. The T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet β-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind β-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses. The present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1β decreased. Ginseng extract preserved normal islet morphology, increased nascent β-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing β-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to β-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance β-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

Impact of COVID-19 vaccination on seminal and systemic inflammation in men

Expedited development of SARS-CoV-2 vaccines led to public concerns regarding impacts of the novel vaccine on gametes in patients seeking assisted reproduction. In cases of an acute intermittent illness or fever in men, it is often advised to postpone ART treatments so that efforts can be made to enhance wellbeing and improve sperm parameters. However, it is unknown whether sperm parameters are altered in the acute (24–72 hour) phase following COVID-19 vaccination. We performed a longitudinal cohort study of 17 normospermic male patients attending a fertility clinic for semen analysis. Semen and matched peripheral blood samples were collected prior to vaccination, within 46 + 18.9 hours of vaccine course completion (acute) and at 88.4 + 12 days (3 months) post-vaccination. No overall change from baseline was seen in symptoms, mean volume, pH, sperm concentration, motility, morphology or DNA damage in the acute or long phase. Seminal plasma was found to be negative for anti-SARS-CoV2 Spike antibody detection, and MCP-1 levels showed an acute but transient elevation post-vaccine, while IL-8 was marginally increased 3 months after completion of vaccination. A modest, positive correlation was noted between serum levels of the anti-inflammatory cytokine IL-10 and self-reported symptoms post-vaccine. Our findings are reassuring in that no significant adverse effect of vaccination was noted and provide evidence to support the current recommendations of reproductive medicine organisations regarding timing of vaccination during fertility treatment.

Astaxanthin treatment decreases pro-inflammatory cytokines and improves reproductive outcomes in patients with polycystic ovary syndrome undergoing assisted reproductive technology: A randomized clinical trial.

In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) -6, IL-1β were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. A significant decrease in IL-6 and IL-1β concentrations (both, P=<0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P= 0.01), the MII oocyte count (P= 0.007), oocyte maturity rate (MII %) (P= 0.02) and number of frozen embryos (P= 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings.

Effect of Curcuma longa Extract as Adjuvant Therapy on IL-6 Serum Levels in Leprosy Type 1 Reaction Patients

Type 1 leprosy reaction / Reversal reaction (RR) is an inflammatory episode in existing leprosy lesions and aggravates the pain rate. Long-term therapy with steroids causes a variety of side effects, so an adjuvant therapy alternative is needed to alleviate steroid use. Curcuma longa rhizome extract has become an anti-inflammatory therapy choice in various previous inflammatory diseases. This study aims to determine the anti-inflammatory effect of Curcuma longa rhizome extract as an adjuvant therapy for reversal reaction patients by analyzing serum levels of IL-6 as a marker of inflammation. The pre and post-test randomized single-blinded controlled trial was conducted on two groups, namely control (RR patients with steroid therapy &amp; placebo) and treatment (steroid therapy &amp; Curcuma longa rhizome extract 1 gram/day). IL-6 serum levels were analyzed from sampling before and after the intervention for one month. The serum levels of IL-6 post-test in the control group were significantly higher than those of the pre-test. The treatment group showed lower serum levels of IL-6 post-test compared to pre-test, although there was no significant difference. Curcuma longa rhizome extract 1 gram/day for one month as adjuvant therapy for patients with type 1 leprosy reaction did not significantly reduce serum IL-6 levels.

Blood smears analysis: a valuable tool for profiling circulating erythrocytes and leukocytes in mouse model of leishmaniasis

Although blood smear analysis can yield valuable insights into the health status of laboratory animals, it is not frequently performed in studies involving mouse models of leishmaniasis. Thus, to underscore its importance, we conducted microscopic evaluation of blood smears prepared from 10 µL of blood from L. (L.) amazonensis-infected BALB/c mice. Subsequently, we explored potential correlations between the identified hematological alterations, clinical evaluation data, and serum levels of total proteins (TP), albumin (Alb), globulins (Glob), IL-17A, and IL-10. Our findings revealed that infected mice exhibited an increased erythrocyte count, alongside a higher prevalence of microcytic and hypochromic erythrocytes. Moreover, it was observed elevated relative and absolute numbers of neutrophils and monocytes and reduced relative and absolute numbers of lymphocytes. A significant proportion of monocytes and lymphocytes in infected animals displayed reactive features. The relative number of lymphocytes was negatively correlated with the serum levels of Glob. Furthermore, the frequency of reactive lymphocytes was positively correlated with the serum levels of Glob and IL-17A. There was also a positive correlation between the absolute number of neutrophils and the serum levels of IL-17A and the frequency of reactive monocytes and the serum levels of Glob. Therefore, these findings, collectively, underscore the importance of blood smear analysis for elucidating both the quantitative and qualitative hematological changes experimentally induced by Leishmania infection. Integration of this technique into research protocols involving different mouse models of leishmaniasis holds immense potential for advancing our knowledge of this infectious disease and enhancing clinical management strategies.

IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition.

Expansion of CD4+CD28null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4+CD28null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4+CD28null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4+CD28null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4+CD28null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4+CD28null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4+CD28null T-lymphocytes.

The Effects of Dietary Pterostilbene on the Immune Response, Antioxidant Function, and Jejunal Structure of Broilers.

This experiment was carried out to investigate the effect of pterostilbene (PTE) supplementation in feed on Arbor Acres broilers in terms of serum biochemical parameters, immune and inflammatory responses, antioxidant status, and intestinal morphological structure. For a duration of 42 days, a total of 480 1-day-old Arbor Acres broilers were randomly divided into four groups. Each group was assigned to receive either the basal diet or the basal diet supplemented with 200, 400, or 600 mg/kg of PTE. Each treatment consisted of eight replicates, with 15 chicks per replicate. In comparison with the control group, three PTE treatments significantly increased the lymphocyte transformation rate in the spleen of broilers. The automated biochemical analysis, enzyme-linked immunosorbent assay, and RT-qPCR analysis kits found that 400 mg/kg of PTE significantly increased the serum levels of complement C3, IL-4, and iNOS; reduced the serum levels of IL-6, TNF-α, and mRNA levels of the genes IL-6, IL-8, TNF-α, NLRP3, and IFN-γ; significantly improved the activities of antioxidant enzymes including CAT, GSH-Px, and T-SOD in the jejunum; and significantly reduced the MDA contents in the serum and jejunum of broilers. Nikon microscope observations and ImagePro Plus 6.0 measure results found that 400 mg/kg of PTE supplementation significantly reduced the relative length and weight of the jejunum and improved the jejunal villi structure, resulting in increased intestinal villi, deepened crypt, and an enhanced ratio of villi height to crypt depth (VH/CD). RT-qPCR and Western blot found that dietary PTE also resulted in increased mRNA levels of the genes Claudin-2, Occludin, ZO-1, and Sirt1, and decreased NF-κB protein levels in the jejunum. The results of this study demonstrated that dietary PTE improved the immune function and intestinal health of broilers by reducing inflammation and increasing the antioxidant capacity of the animals.

Lenalidomide and dexamethasone for Rosai-Dorfman disease: a single arm, single center, prospective phase 2 study

Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25mg days 1-21 plus dexamethasone 40mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p<0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n=9) and 70% (n=16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n=7) complete remission, 57% (n=13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p=0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p=0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n=12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n=2, 9%), glucose intolerance (n=2, 9%), edema (n=2, 9%), insomnia (n=1, 4%), and tremor (n=1, 4%). Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.

Recombinant Schistosoma japonicum cystatin alleviates acute liver injury in mice by inhibiting endoplasmic reticulum stress, inflammation and hepatocyte apoptosis

To investigate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute liver injury induced by lipopolysaccharide (LPS) and D-GalN in mice. Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling (n=18), and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling. The survival of the remaining 10 mice in each group within 24 h was observed. Serum levels of ALT, AST, TNF-α and IL-6 of the mice were measured, and liver pathologies was observed with HE staining. The hepatic expressions of macrophage marker CD68, Bax, Bcl-2 and endoplasmic reticulum stress (ERS)-related proteins were detected using immunohistochemistry or immunoblotting, and TUNEL staining was used to detect hepatocyte apoptosis. The survival rates of PBS- and rSj-Cys-treated mouse models of acute liver injury were 30% and 80% at 12 h and were 10% and 60% at 24 h after modeling, respectively; no death occurred in the two control groups within 24 h. The mouse models showed significantly increased serum levels of AST, ALT, IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax, lowered expression of Bcl-2, increased hepatocyte apoptosis, and up-regulated expressions of ERS-related signaling pathway proteins GRP78, CHOP and NF-κB p-p65. Treatment of the mouse models significantly lowered the levels of AST, ALT, IL-6 and TNF-α, alleviated liver pathologies, reduced hepatic expressions of CD68, Bax, GRP78, CHOP and NF-κB p-p65, and enhanced the expression of Bcl-2. In the normal control mice, rSj-Cys injection did not produce any significant changes in these parameters compared with PBS. rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS, attenuating inflammation and inhibiting hepatocyte apoptosis.

Completion rates and myelosuppression degrees of cancer patients receiving radiotherapy or chemoradiotherapy unchanged regardless of delay duration after Omicron infection

This study aimed to investigate impacts of Omicron infection on cancer patients in China. A retrospective study was conducted, including 347 cancer patients undergoing radiotherapy or chemoradiotherapy between July 2022 and March 2023. Three groups involved: 108 patients without SARS-CoV-2 infection (non-COVID-19 group), 102 patients beginning treatment 10 days after first SARS-CoV-2 infection (≥ 10 days COVID-19 group), and 137 patients beginning treatment less than 10 days after first SARS-CoV-2 infection (< 10 days COVID-19 group). SAA, hsCRP, ALT, etc., were used to assess COVID-19 infection. Serum levels of SAA, hsCRP and IL-6 were all raised in two COVID-19-infected groups (SAA < 0.01, hsCRP < 0.01, IL-6 < 0.05), but PCT, ALT, LDH and HBDH levels were only elevated in ≥ 10 days COVID-19 group (PCT = 0.0478, ALT = 0.0022, LDH = 0.0313, HBDH = 0.0077). Moreover, moderate and severe infected cases were higher in ≥ 10 days COVID-19 group than < 10 days COVID-19 group (12/102 vs 5/137, p = 0.0211), but no significance in myelosuppression and completion rates among three groups. Omicron infection led to inflammation, liver and cardiovascular injury on cancer patients, but delay duration of radiotherapy or chemoradiotherapy after infection did not affect the completion rates and myelosuppression of current therapy. Besides, severity of Omicron infection was even worse among cancer patients who received delayed treatment.