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Background: Allergy immunotherapy (AIT), a treatment approach for allergic rhinitis (AR), is recognized for its potential to modify the disease course beyond mere symptom relief. Interleukin‐36γ (IL‐36γ), a key player in immune responses, has been implicated in promoting eosinophilic inflammation in AR by activating eosinophils. We aimed to investigate the effect of IL‐36γ on group II lymphoid cell (ILC2) in AR patients who underwent sublingual immunotherapy (SLIT). Methods: Twenty‐four AR patients were enrolled and administered with SLIT. Serum proteins of IL‐36γ, interleukin‐5 (IL‐5), and interleukin‐13 (IL‐13) during SLIT were quantitatively assessed using enzyme‐linked immunosorbent assay (ELISA). The proportion of ILC2 was determined by flow cytometry. Sorted ILC2s were stimulated by IL‐36γ and ILC2 cell differentiation, and type II cytokines expression were examined. Results: SLIT treatment decreased the serum protein levels of IL‐36γ, IL‐5, IL‐13, and the proportion of ILC2 significantly. IL‐36γ suppressed the proliferation of ILC2 by inhibiting the levels of ILC2 transcription factor. IL‐36γ also inhibited IL‐5 and IL‐13 expression from ILC2. Conclusion: The changes of IL‐36γ during SLIT were related to the inhibited function of ILC2, implying that IL‐36γ may be used as a new biomarker for monitoring the efficacy of SLIT in AR. [ABSTRACT FROM AUTHOR]

Overactive inflammatory responses contribute to progressive cardiac dysfunction after myocardial infarction (MI). Mesenchymal stem cell (MSC) has generated significant interest as potent immune modulators that can regulate excessive immune responses. We hypothesized that intravenous (iv) administration of human umbilical cord-derived MSC (HucMSC) exerts systemic and local anti-inflammation effects, leading to improved heart function after MI. In murine MI models, we confirmed that single iv administration of HucMSC (30 × 10 4 ) improved cardiac performance and prevented adverse remodeling after MI. A small proportion of HucMSC is trafficked to the heart, preferentially in the infarcted region. HucMSC administration increased CD3+ T cell proportion in the periphery while decreased T cell proportion in both infarcted heart and mediastinal lymph nodes (med-LN) at 7-day post-MI, indicating a systematic and local T cell interchange mediated by HucMSC. The inhibitory effects of HucMSC on T cell infiltration in the infarcted heart and med-LN sustained to 21-day post-MI. Our findings suggested that iv administration of HucMSC fostered systemic and local immunomodulatory effects that contributed to the improvement of cardiac performance after MI. [ABSTRACT FROM AUTHOR]

Background. Non-small cell lung cancer (NSCLC) is still a slightly less orphan disease after immunotherapy, and routine treatment has low efficiency and adverse events. Ginseng is commonly used in the treatment of NSCLC. The purpose of this study is to assess the efficacy and hemorheological indexes of ginseng and its active components in patients with non-small cell lung cancer. Methods. A comprehensive literature search was performed in PubMed, the Cochrane Library, Medline (Ovid), the Web of Science, Embase, CKNI, Wan Fang, VIP, and SinoMed up to July 2021. Only randomized controlled trials evaluating ginseng in combination with chemotherapy versus chemotherapy alone in NSCLC patients were included. Primary outcomes included patients' condition after using ginseng or its active components. Secondary outcomes included changes in immune cells, cytokines, and secretions in serum. Data were extracted by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was applied for the included studies. Systematic review and meta-analysis were performed by RevMan 5.3 software. Results. The results included 1480 cases in 17 studies. The results of the integration of clinical outcomes showed that the treatment of ginseng (or combination of ginseng with chemotherapy) can improve the quality of life for patients with NSCLC. Analysis of immune cell subtypes revealed that ginseng and its active ingredients can upregulate the percentages of antitumor immunocyte subtypes and downregulate the accounts of immunosuppressive cells. In addition, a reduction of the inflammatory level and an increase of antitumor indicators in serum were reported. Meta-analysis showed that Karnofsky score: WMD = 16, 95% CI (9.52, 22.47); quality-of-life score: WMD = 8.55, 95%CI (6.08, 11.03); lesion diameter: WMD = −0.45, 95% CI (−0.75, −0.15); weight: WMD = 4.49, 95% CI (1.18, 7.80); CD3+: WMD = 8.46, 95% CI (5.71, 11.20); CD4+: WMD = 8.45, 95% CI (6.32, 10.57)+; CD8+: WMD = −3.76, 95% CI (−6.34, −1.18); CD4+/CD8+: WMD = 0.32, 95% CI (0.10, 0.53); MDSC: WMD = −2.88, 95% CI (−4.59, −1.17); NK: WMD = 3.67, 95% CI (2.63, 4.71); Treg: WMD = −1.42, 95% CI (−2.33, −0.51); CEA: WMD = −4.01, 95% CI (−4.12, −3.90); NSE: WMD = −4.00, 95% CI (−4.14, −3.86); IL-2: WMD = 9.45, 95% CI (8.08, 10.82); IL-4: WMD = −9.61, 95% CI (−11.16, −8.06); IL-5: WMD = −11.95, 95% CI (−13.51, −10.39); IL-6: WMD = −7.65, 95% CI (−8.70, −6.60); IL-2/IL-5: WMD = 0.51, 95% CI (0.47, 0.55); IFN-γ: WMD = 15.19, 95% CI (3.16, 27.23); IFN-γ/IL-4: WMD = 0.91, 95% CI (0.85, 0.97); VEGF: WMD = −59.29, 95% CI (−72.99, −45.58); TGF-α: WMD = −10.09, 95% CI (−12.24, −7.94); TGF-β: WMD = −135.62, 95% CI (−147.00, −124.24); TGF-β1: WMD = −4.22, 95% CI (−5.04, −3.41); arginase: WMD = −1.81, 95% CI (−3.57, −0.05); IgG: WMD = 1.62, 95% CI (0.18, 3.06); IgM: WMD = −0.45, 95% CI (−0.59, −0.31). All results are statistically significant. No adverse events were reported in the included articles. Conclusion. It is a reasonable choice to use ginseng and its active components as adjuvant therapy for NSCLC. Ginseng is helpful for NSCLC patients' conditions, immune cells, cytokines, and secretions in the serum. [ABSTRACT FROM AUTHOR]

Allergic rhinitis and asthma are common airway allergic diseases, the incidence of which has increased annually in recent years. The human body is frequently exposed to allergens and environmental irritants that trigger immune and inflammatory responses, resulting in altered gene expression. Mounting evidence suggested that epigenetic alterations were strongly associated with the progression and severity of allergic diseases. Noncoding RNAs (ncRNAs) are a class of transcribed RNA molecules that cannot be translated into polypeptides and consist of three major categories, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Previous studies showed that ncRNAs were involved in the physiopathological mechanisms of airway allergic diseases and contributed to their occurrence and development. This article reviews the current state of understanding of the role of noncoding RNAs in airway allergic diseases, highlights the limitations of recent studies, and outlines the prospects for further research to facilitate the clinical translation of noncoding RNAs as therapeutic targets and biomarkers. [ABSTRACT FROM AUTHOR]

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on eosinophil activation, atopic sensitization, and systemic inflammation in allergic diseases has rarely been investigated. This study aimed to investigate the relationship between NGAL, eosinophil cationic protein (ECP), cytokines, and allergen-specific immunoglobulin E (sIgE) in allergic diseases. A total of 136 patients with allergies and 58 healthy individuals were evaluated. The concentrations of NGAL, ECP, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), sIgE, total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) were measured. The transforming growth factor-β1 (TGF-β1) level was measured as a profibrotic marker of bronchial asthma. Allergic patients had significantly higher NGAL, ECP, and hsCRP levels than healthy individuals. However, there was no significant difference in NGAL levels between patients with positive and negative ECP tests and those with high and low sIgE scores. Asthmatic patients with elevated NGAL exhibited a significantly higher TGF-β1 level than those without elevated NGAL. However, no significant difference was observed in the ECP, IL-5, and sIgE levels between the two groups. Among the patients with a positive ECP test, subjects with elevated hsCRP had two times higher NGAL levels than those without elevated hsCRP. NGAL was positively correlated with TNF-α, TGF-β1, and hsCRP, but not with ECP, IL-5, tIgE, and sIgE. An elevated NGAL level led to a 1.3-fold increase in the prevalence of high TGF-β1 (odds ratio: 1.31; 95% CI: 1.04–2.58; P < 0.001). In conclusion, NGAL elevation may be more closely linked to allergic inflammation and a possible fibrotic change in the airways than to the severity of eosinophil activation and atopic sensitization. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection can regulate the expression of a wide range of noncoding microRNAs (miRNAs), in which mir-19a-3p can participate in airway inflammatory response by regulating 5-lipoxygenase (5-LO) pathway. RSV nonstructural protein (NS) 1 is involved in the airway hyperresponsiveness during RSV infection.Methods: The expression levels of miR-19a-3p and inflammatory signaling-related indicators were detected using quantitative real-time PCR and western blot analyses on the A549 cells transfected with NS1 expression plasmids (pNS1). The 5-LO-mediated inflammatory signaling pathway was assessed when the miR-19a-3p or 5-LO was inhibited.Results: The immunofluorescence analysis showed that the plasmid-mediated NS1 protein was observed in both the cytoplasm and nucleus. The expression level of miR-19a-3p was significantly upregulated in the pNS1 or RSV-treated cells, which was reversed by the NS1 small interfering RNA. In addition, pNS1 also upregulated the expression of 5-LO, interleukin-5 (IL-5), and leukotriene B4 (LTB4), which was also significantly inhibited by the miR-19a-3p antagonists. The 5-LO inhibitor MK886 prevented the increase in the expression level of IL-5 induced by pNS1.Conclusions: These results suggested that the RSV NS1 might play an important role in the pathogenesis of RSV by activating the 5-LO and subsequent inflammatory cytokines through miR-19a-3p. [ABSTRACT FROM AUTHOR]

Juglans regia (J. regia) has been used traditionally to treat cough and asthma. The present study evaluates the immunomodulatory and anti-inflammatory potential of J. regia against ovalbumin (OVA)-induced allergic asthma. Intraperitoneal sensitization proceeded by intranasal challenge with OVA was used to induce allergic asthma. BALB/c mice were treated with methanol, n-hexane, and ethyl acetate extracts of J. regia and methylprednisolone one week after 2nd sensitization with OVA and continued for 7 days. mRNA expression levels of IL-4, IL-5, IL-13, AQP-1, AQP-5 TNF-α, TGF-β, and NF-kB were determined using reverse transcription polymerase chain reaction. Hematoxylin and eosin, and periodic acidic-Schiff stains were used for histopathological studies of lung tissues. The data presented all three extracts of J. regia significantly ameliorated airway inflammation by reducing expression levels of IL-4, IL-5, and IL-13 and TNF-α in OVA-treated mice. The suppression of goblet cells hyperplasia and inflammatory cells infiltration by J. regia involved low TGF-β and NF-kB levels. Pretreatment with J. regia also increased the AQP-1 and AQP-5 expression levels in mice treated with OVA. This study supported the traditional use of J. regia and proposed that J. regia ameliorated allergic asthma by suppression of proinflammatory cytokines and elevation of AQP-1 and AQP-5 expression levels. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 μg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis. [ABSTRACT FROM AUTHOR]

There is a limited number of clinical studies on interferon (IFN) levels in human brucellosis. The novel group of interferons, type III interferons, which consists of four IFN-λ (lambda) molecules called IFN-λ1 or interleukin-29 (IL-29), IFN-λ2 or IL-28A, IFN-λ3 or IL-28B, and IFN-λ4, is not fully known. This study is one of the first studies of IL-28A and IL-29 levels in brucellosis cases at the end of their treatment course. A total of 33 acute brucellosis patients were included in this study. We considered changes in the levels of IL-28A and IL-29 in cases with acute brucellosis before and after treatment with standard therapy that referred to the Ayatollah Rohani Hospital in Babol, northern Iran. Of 33 included patients, 22 (66.6%) were males, and 11 (33.4%) were females. The range of patients' age was 49.21 ± 17.70 years. Serum IL-29 and IL-28A (acute form: 56.4 ± 30.32 pg/mL and 48.73 ± 27.72 pg/mL, respectively, and posttreatment: 40.15 ± 20.30 pg/mL and 38.79 ± 22.66 pg/mL, respectively) levels were elevated significantly in acute brucellosis than after treatment (p < 0.05). These findings indicate that considering biomarker levels in brucellosis patients may indicate the chronicity of infection. In conclusion, we suggest that IL-29 and IL-28A levels may be valuable biomarkers for follow-up patients with brucellosis. [ABSTRACT FROM AUTHOR]

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy. [ABSTRACT FROM AUTHOR]

Experimental work of the last two decades has revealed the general steps of the wound healing process. This complex network has been organized in three sequential and overlapping steps. The first step of the inflammatory phase is an immediate response to injury; primary sensory neurons sense injury and send danger signals to the brain, to stop bleeding and start inflammation. The following target of the inflammatory phase, led by the peripheral blood mononuclear cells, is to eliminate the pathogens and clean the wound. Once this is completed, the inflammatory phase is resolved and homeostasis is restored. The aim of the proliferative phase, the second phase, is to repair wound damage and begin tissue remodeling. Fibroplasia, reepithelialization, angiogenesis, and peripheral nerve repair are the central actions of this phase. Lastly, the objective of the final phase is to complete tissue remodeling and restore skin integrity. This review provides present day information regarding the status of the participant cells, extracellular matrix, cytokines, chemokines, and growth factors, as well as their interactions with the microenvironment during the wound healing process. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) and allergic diseases are result of a poor functioning immune system, giving dominance to either T-helper 1 (Th1) or T-helper 2 (Th2) diseases, respectively. Studies have stated that there seems to be a relationship present between the immune response subsets. This study was designed to examine the association between RA and respiratory allergic diseases in Korean adults. The study utilized the KNHANES 2013–2015 data and excluded individuals diagnosed with RA before being diagnosed with allergic diseases, using age at clinical diagnosis. Total of 253 RA patients were matched 1 : 1 with non-RA patients by a propensity score, using sex and age as matched variables. Multivariate conditional logistic regression analyses were used to evaluate for association between RA and respiratory allergic diseases in the matched 506 participants. RA was associated with an increased risk of prevalence of respiratory allergic diseases with an OR of 1.51 (95% CI, 1.31–1.75), adjusted for socioeconomic demographic variables. The adjusted OR for prevalence of RA among participants with prevalence of asthma and allergic rhinitis was as follows: 3.12 (95% CI, 2.77–3.51) and 1.39 (95% CI, 1.16–1.67). Participants with prevalence of asthma in particular had an increased risk of developing prevalence of RA. Based on our findings, Th1 and Th2 diseases may indeed coexist, and one pathway may stimulate or contribute towards the onset of the other. [ABSTRACT FROM AUTHOR]

What is known and Objective: To evaluate the effects of an olmesartan/amlodipine single pill combination compared with olmesartan or amlodipine monotherapies on blood pressure control, lipid profile, insulin sensitivity and some adipocytokines levels. Methods: Two hundred and seventy-six patients were enroled in the study and were randomly assigned to take olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20 mg/5 mg for 12 months. We evaluated at the baseline, and after 6 and 12 months: body weight, body mass index, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), resistin (r), interleukin-1β (IL-1β) and interleukin-5 (IL-5). At the baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity ( M value). Results and Discussion: There was a similar decrease in SBP and DBP after 6 and 12 months in all groups, even if olmesartan/amlodipine combination gave a major decrease in SBP and DPB compared with amlodipine and olmesartan monotherapies. Olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. Olmesartan/amlodipine combination decreased FPI and HOMA index and increased M value both compared with baseline and compared with olmesartan and amlodipine monotherapies. Both olmesartan and olmesartan/amlodipine increased ADN and reduced r, without significant differences between the two groups. Regarding interleukins, no differences emerged in group to group comparison. What is new and Conclusion: Olmesartan/amlodipine combination resulted more effective than olmesartan and amlodipine monotherapies in reducing blood pressure, and in increasing insulin sensitivity parameters, but not resulted more effective in improving adipocytokines and interleukins levels analysed, compared with amlodipine or olmesartan monotherapy in hypertensive patients in this double-blind, randomized clinical trial. [ABSTRACT FROM AUTHOR]