IL-10 Levels Research Articles

Effects of D3K2 With Periodontal Therapy in Diabetes Mellitus and Stage I-II Periodontitis Patients.

The aim of this study is to look into the clinical and biochemical outcomes of D3K2 supplementation in addition to nonsurgical periodontal treatment (NSPT) for patients suffering from diabetes mellitus (DM) and periodontitis. Thirty-eight participants with DM and periodontitis were randomized into two different groups. The test group provided NSPT with D3K2 whereas the control group received NSPT with placebo. Clinical periodontal parameters were recorded and serum and gingival crevicular fluid (GCF) were sampled at baseline and at the third and the sixth months after treatment. Glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 25(OH)D3, parathyroid hormone (PTH), calcium (Ca) and magnesium (Mg) values were determined in blood samples. GCF and serum interleukin (IL)-1β and IL-10 levels were analyzed using enzyme-linked immunosorbent assay. All clinical periodontal parameters were importantly decreased at the third and sixth months after treatment compared to baseline in both groups. At the sixth month, 25(OH)D3 levels in the test group were observed to be statistically significantly higher than in the control group (p = 0.02). Serum IL-1β showed a statistically significant decrease at the sixth month compared to baseline and the third month in control group. According to this study, there is limited additional benefit of D3K2 given with NSPT in individuals with DM and periodontitis.

Cytokine profile of oral fluid in case of traumatic fractures of the lower jaw and the presence of third molars in patients` oral cavity

Objective. To analyze the level of cytokines in the oral fluid of patients with traumatic fractures of the mandible in the presence of third molars, to establish the influence of the latter on the oral cavity homeostasis, to determine the most informative indicators. Materials and methods. 82 people aged 18–60 years took part in the study, they were divided into 3 groups. Group 1 contained 43 patients with mandibular fracture and having more than two third molars. Group 2 consisted of 18 patients with mandibular fracture, without third molars. Group 3 included 21 people without a fracture of the mandible, who had more than two-thirds of the molars. Group 4 (control) contained the data of somatically and dentally healthy individuals, borrowed from special literature. The levels of IL-1β, IL-6, IL-8, and TNF-a in OF were determined using standard enzyme immunoassay kits. The data were processed statistically. Results. A comparison of the indicators of groups 1 and 3 revealed a significant increase in the level of IL-6 z = 4.15 (H = 20.43; p = 0.0001) and the level of IL-8 z = 3.08 (H = 12.29; p = 0.0064) in patients with a jaw fracture. A considerable increase in IL-8 levels was determined in the individuals from group 2 compared with group 3 – z = 2.74 (H = 12.29; p = 0.0064). The comparison of groups 1 and 4 in terms of TNF-a showed a tendency to a significant difference of z = 1.60 (H = 4.65; p = 0.19), and the data of group 2 in comparison with group 4 were significantly higher than z = 1.97 (H = 4.65; p = 0.19). Comparing the results of groups 3 and 4 with each other we revealed a considerable difference of z = 1.75 (H = 4.65; p = 0.19). Conclusion. The profile of cytokines level in the OF indicates that the presence of third molars in the oral cavity in mandibular fractures affects the homeostasis of the oral cavity negatively, which is the reason for expanding the indications for their removal in order to prevent infectious and inflammatory complications.

Immunostimulatory Activity of a Mixture of Platycodon grandiflorum, Pyrus serotine, Chaenomeles sinensis, and Raphanus sativus in RAW264.7 Macrophages.

In this study, a mixture of Platycodon grandiflorum, Pyrus serotina, Chaenomeles sinensis, and Raphanus sativus (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E2 (PGE2) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of IL-4. PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages.

Correlation of Triethylamine N-oxide (TMAO), LPS, and TNF-Alpha Levels With Clinical Features of the Disease in Patients With and Without Septic Shock Infected With COVID-19 Virus

BackgroundInflammation is a response of the immune system to protect the body against various diseases or injuries. Serum trimethylamine N-oxide (TMAO) levels may vary depending on age, gender, habits, comorbidities, and microbiota. AimsIn this study, we investigated whether TMAO levels have diagnostic significance and their potential as a marker in the early diagnosis of the disease. Another aim of the research was to identify changes in TMAO levels as a reflection of the deterioration in the microflora, and IL-6, IL-10, IL-1β, TNF-alpha, and LPS levels in patient groups. Then, we recognized relationships between these parameters in patients infected with COVID-19 without septic shock and with COVID-19 who were without transmission of COVID-19 in septic shock. Study DesignA total of 160 patients were investigated, including 40 patients infected with COVID-19 without septic contact, 40 patients with COVID-19 positive septic shock, 40 patients with COVID-19 negative septic shock, and 40 healthy individuals as the control group. ResultsTNF-α and IL-1β levels were significantly lower (P < 0.001) and IL-6 and IL-10 levels were significantly higher (P < 0.001) in patient groups than in control groups. IL-1β showed a significant decrease, especially in the groups infected with COVID-19. Although IL-6, increased even more in the groups infected with COVID-19. ConclusionsLPS level was remarkably high in the sepsis group infected with COVID-19 compared to the other groups. TMAO level was significantly higher (P < 0.001) in the sepsis group. Therefore, TMAO is a potential biomarker in sepsis and septic shock.

Biochemical, immunological markers, histology and ultrastructural changes of open wound healing in rats treated with ethyl acetate extract of Zingiber zerumbet rhizomes

Research on plant-based wound healing agents has been one of the current developing areas in modern biomedical science. This study aimed to assess the effects of ethyl acetate extract of Zingiber zerumbet rhizome (ZZRE) on open wound healing activity in Wistar rats. Ninety male Wistar rats (220–320 g) were divided into three groups treated with phosphate buffered saline (PBS) (negative control), Solcoseryl gel (positive control), and 10 % ZZRE (treatment group), respectively. Six circular full-skin thickness wounds of 6.0 mm in diameter were induced bilaterally on the dorsal surface of each rat. Six rats were sacrificed on Day-1, Day-3, Day-6, Day-10 and Day-14 respectively from each group after wound induction. All data obtained are considered statistically significant at p < 0.05. Macroscopic observations showed that the 10 % ZZRE treated wounds healed faster compared to other groups. The wound closure percentage showed that the wound treated with 10 % ZZRE is significantly higher (p < 0.05) than the PBS group on Day-6, Day-10 and Day-14. Protein levels of the 10 % ZZRE group decreased significantly at Day-1 compared to the PBS group and significantly (p < 0.05) higher at Day-14 compared to both control groups. The hexosamine and uronic acid levels of the 10 % ZZRE group showed a significant (p < 0.05) decrease on Day-14. Conversely, hydroxyproline levels showed significant (p < 0.05) increase starting from Day-3 until Day-14. As for the immunological markers, the level of total TGF-β1 of the 10 % ZZRE group was significantly (p < 0.05) higher than the PBS group on Day-14, whereas the level of IL-10 on the wound tissue of the 10 % ZZRE group was significantly (p < 0.05) lower than the PBS group on Day-1 but significantly (p < 0.05) higher on Day-10 and Day-14 compared to both control groups. Histological observation showed that the wounds treated with 10 % ZZRE infiltrated with lesser inflammatory cells while collagen deposition was denser as compared to both control groups. Based on the result obtained, it is clearly proven that treatment of 10 % ZZRE on open wound healing in rats, showed that the extract was effective in healing the wound and accelerated the healing process. Therefore, the 10 % ZZRE tested has the potential to be developed as an alternative wound healing agent in the future.

Exploration of the diagnostic value and expression levels of blood IFN-γ and IL-2 in patients with lymph node tuberculosis

Symptoms and signs of lymph node tuberculosis(LNTB) lack specificity, which making identification difficult and increasing the likelihood of missed or misdiagnosed cases.This study aimed to examine the diagnostic effectiveness of IFN-γ/IL-2,for differentiating LNTB from non-tuberculous lymphadenopathy(Non-TB-LAP) , as well as to analyze the variations in their expression levels among different subgroups. Ultimately, 95 patients with enlarged lymph nodes were enrolled in the study. Based on the diagnostic criteria of LNTB, 38 patients were Confirmed LNTB, 28 patients were Clinically diagnosed LNTB and 29 patients were Non-TB-LAP. The cut-off values of IFN-γ/IL-2 for differentiating LNTB from Non-TB-LAP were 58.267 pg/mL and 12.207 pg/mL respectively, through receiver operating characteristic curves. In patients with LNTB and Non-TB-LAP, the sensitivity of IFN-γ/IL-2 in parallel was 83.08%, which was higher than that of IFN-γ(p<0.05). When IFN-γ/IL-2 were combined in tandem, the specificity was the highest at 93.1%. The median level of IL-2 in patients with Confirmed LNTB was higher than that of Clinically diagnosed LNTB(p＜0.05). In conclusion, IFN-γ/IL-2 have shown good diagnostic efficacy in LNTB. In addition, in patients diagnosed as LNTB, the expression level of IL-2 may be related to the burden of mycobacterium tuberculosis in the body and the activity of tuberculosis infection.

Construction and verification of pancreatic fistula risk prediction model after pancreaticoduodenectomy based on ensemble machine learning

Objective: To construct an ensemble machine learning model for predicting the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy and evaluate its application value. Methods: This is a research on predictive model. Clinical data of 421 patients undergoing pancreaticoduodenectomy in the Department of Pancreatic Surgery,Union Hospital, Tongji Medical College,Huazhong University of Science and Technology from June 2020 to May 2023 were retrospectively collected. There were 241 males (57.2%) and 180 females (42.8%) with an age of (59.7±11.0)years (range: 12 to 85 years).The research objects were divided into training set (315 cases) and test set (106 cases) by stratified random sampling in the ratio of 3∶1. Recursive feature elimination is used to screen features,nine machine learning algorithms are used to model,three groups of models with better fitting ability are selected,and the ensemble model was constructed by Stacking algorithm for model fusion. The model performance was evaluated by various indexes,and the interpretability of the optimal model was analyzed by Shapley Additive Explanations(SHAP) method. The patients in the test set were divided into different risk groups according to the prediction probability (P) of the alternative pancreatic fistula risk score system (a-FRS). The a-FRS score was validated and the predictive efficacy of the model was compared. Results: Among 421 patients,CR-POPF occurred in 84 cases (20.0%). In the test set,the Stacking ensemble model performs best,with the area under the curve (AUC) of the subject's work characteristic curve being 0.823,the accuracy being 0.83,the F1 score being 0.63,and the Brier score being 0.097. SHAP summary map showed that the top 9 factors affecting CR-POPF after pancreaticoduodenectomy were pancreatic duct diameter,CT value ratio,postoperative serum amylase,IL-6,body mass index,operative time,albumin difference before and after surgery,procalcitonin and IL-10. The effects of each feature on the occurrence of CR-POPF after pancreaticoduodenectomy showed a complex nonlinear relationship. The risk of CR-POPF increased when pancreatic duct diameter<3.5 mm,CT value ratio<0.95,postoperative serum amylase concentration>150 U/L,IL-6 level>280 ng/L,operative time>350 minutes,and albumin decreased by more than 10 g/L. The AUC of a-FRS in the test set was 0.668,and the prediction performance of a-FRS was lower than that of the Stacking ensemble machine learning model. Conclusion: The ensemble machine learning model constructed in this study can predict the occurrence of CR-POPF after pancreaticoduodenectomy,and has the potential to be a tool for personalized diagnosis and treatment after pancreaticoduodenectomy.

Potential of Pre-Operative Serum Interleukin-6 as a Biomarker for Colorectal Cancers

The diagnosis of colorectal cancers (CRC) at its early stage is challenging due to lack of early markers. Current diagnostic tests are either invasive or show low sensitivity. Interleukins are known to elevate and play important roles in the development and progression of the CRC. The studies on interleukin profiles of CRC patients are mainly confined to Caucasian populations while South Asian data are sparse. Therefore, the aim of this study was to investigate the serum IL-6 and IL-10 levels in a cohort of Sri Lankan CRC patients and explore their potential to be used as markers for early diagnosis/prognosis of CRC. Blood samples from 35 CRC patients and 35 healthy volunteers were obtained after informed consent. Their clinical findings and carcinoembryonic antigen (CEA) levels were recorded. Concentrations of IL-6 and IL-10 were measured using ELISA according to manufacturer’s protocols. Mean serum [IL-6] was found to be significantly higher in CRC patients than controls (p&lt;0.05). The mean [IL-10]showed no difference to that of controls. (p&gt;0.05). Interestingly, the [IL-6] in CRC patients were correlated with the disease stage (Stage I-0.16pg/ml; stage II-7.01pg/ml; stage III-15.8pg/ml and stage IV-35.48pg/ml). CEA levels were not correlated with the disease stage or withIL-6 levels. This study provided preliminary evidence to use IL-6 as a potential biochemical marker for the diagnosis of CRC inaddition to CEA. Furthermore, IL-6 could be a marker for prognosis of CRC. Further studies with higher patient samples are needed to validate the results of this study.

Effects of chronic stress on rat heart function following regional ischemia: a sex-dependent investigation.

Chronic psychological stress is a recognized, yet understudied risk factor for heart disease, with potential sex-specific effects. We investigated whether chronic stress triggers sex-dependent cardiac dysfunction in isolated Wistar rat hearts subjected to ischemia-reperfusion injury. The experimental cohort underwent 1 h of daily restraint stress for 4 wk versus matched controls, followed by euthanasia (sodium pentobarbital) and heart excision for ex vivo perfusion. Blood analysis revealed sex-specific alterations in stress hormones and inflammatory markers. When compared with controls, chronic restraint stress (CRS) males displayed decreased plasma brain-derived neurotrophic factor (BDNF) levels (P < 0.05), whereas CRS females exhibited elevated plasma adrenocorticotropic hormone (ACTH) (P < 0.01) and reduced corticosterone (P < 0.001) alongside lower serum estradiol (P < 0.001) and estradiol/progesterone ratio (P < 0.01). Of note, CRS females showed increased serum cardiac troponin T (P < 0.05) and tumor necrosis factor-α (TNF-α) (P < 0.01) with suppressed interleukin (IL)-1α, IL-1β, IL-6, and IL-10 levels (P < 0.05) when compared with controls. Ex vivo Langendorff perfusions revealed that CRS female hearts displayed impaired postischemic functional recovery for baseline stroke volume (SV, P < 0.01), work performance (P < 0.05), aortic output (AO, P < 0.05), coronary flow (CF, P < 0.01), and overall cardiac output (CO, P < 0.01) when compared with matched controls and CRS males (P < 0.05). Our findings reveal intriguing sex-specific responses at both the systemic and functional levels in stressed hearts. Here, the dysregulation of stress hormones, proinflammatory state, and potential underlying cardiomyopathy in females following the stress protocol renders them more prone to damage following myocardial ischemia. This study emphasizes the importance of incorporating sex as a biological variable in cardiac research focusing on stress-related cardiomyopathy.NEW & NOTEWORTHY Although chronic psychological stress is a risk factor for cardiovascular diseases, the underlying mechanisms remain poorly understood. This study revealed that chronic restraint stress resulted in systemic changes (dysregulated stress hormones, proinflammatory state) and potential cardiomyopathy in females versus controls and their male counterparts. The stressed female hearts also displayed reduced functional recovery following ex vivo ischemia-reperfusion. This highlights the importance of incorporating sex as a biological variable in cardiac research.

An integrated In-Silico-In-Chemico-In-Vitro (iSiCiV) Approach to identify biomarkers to predict the skin sensitisation potential of phytochemicals

BackgroundSkin sensitisation is one of the important regulatory endpoints used to determine whether a given test chemical can elicit an allergic response in susceptible individuals. The in-vitro approaches for predicting skin sensitisation potential for chemicals have been well-developed and widely accepted. Continuous efforts are being made to identify novel solutions to overcome the limitations of the existing approaches. PurposeThe herbal preparations used in dermal therapeutics are frequently found to elicit skin sensitisation, requiring caution. The herbal preparations tend to contain more than one phytochemical. The expected active ingredient may not possess skin sensitisation. However, the other phytochemical traces could pose synergistic and potentiating effects towards enhanced/suppressed skin sensitisation. In this regard, isolation, purification, yield, and in-vitro / in-vivo evaluation of skin sensitisation for all the traces would be time, cost, and animal-consuming. Hence, the regulatory agencies appreciate using computational tools to substantiate in-vitro methods. The regulators have also endorsed using in-silico approaches like quantitative structure-activity relationships (QSAR) and read-across. These approaches are limited to structure-based predictions and in combination with system-level approaches, which comprehensively facilitate a better understanding of complex biological systems. Study designIn the present study, 603 phytochemicals were screened in-silico using OECD QSAR Toolbox. The limitations of the QSAR Toolbox in predicting skin sensitisers were identified. MethodThe systems biology-based approach to complement the QSAR-based prediction was developed, and 41 biomarkers were identified as a determinant of skin sensitisation. The molecules attributed to these biomarkers were predicted as skin sensitisers. ResultsAs a result, 31 phytochemicals were predicted as skin sensitisers. Acrolein, eugenol, formaldehyde, and glycerol were selected for experimental validation of the in-silico predictions using direct peptide reactivity assay (DPRA), KeratinoSens™, and h-CLAT assays representing each key event in skin sensitisation. Further, identified biomarkers were validated in THP-1 and KeratinoSens cell lines using qRT-PCR. Among all genes, IL-8 and CCL4 were upregulated by 6.4 and 5.6 folds, respectively, in THP-1, while AKR1C2 and AKR1C3 were upregulated by 7.8 and 11.1 folds, respectively, in KeratinoSens. IL-8 level was analysed by ELISA and found to be in line with qRT-PCR results. ConclusionThe study proposes a possible strategy based on the “iSiCiV” approach to enhance the prediction of the dermal sensitisation potential of a test compound. The approach offers a robust platform and highlights an opportunity to shift the paradigm of skin sensitisation assay with a better understanding of toxicology mechanisms.

Microglial priming by IFN-γ involves STAT1-mediated activation of the NLRP3 inflammasome.

Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial "priming". Interferon (IFN)-γ is known to cause microglial priming, but the mechanism is unclear. We examined the effects of IFN-γ on gene expression, microglial activation, inflammatory and immune responses and activity of the NLRP3 inflammasome in primary microglia and in the brains of mice. Our results showed that treating microglial cultures with IFN-γ induced a hedgehog-like morphology and upregulated markers of microglial activation (CD86, CD11b) and pro-inflammatory molecules (IL-1β, IL-6, TNF-α, iNOS), while downregulating markers of microglial homeostasis (CX3CR1, CD200R1), anti-inflammatory molecules (MCR1, Arg-1) and neurotrophic factors (IGF-1, BDNF). IFN-γ also upregulated markers of NLRP3 inflammasome activation (NLRP3, caspase-1, gasdermin D, IL-18). This particular transcriptional profiling makes IFN-γ-primed microglia with exaggerated responses upon lipopolysaccharide (LPS) stimulation. The level of NLRP3, caspase-1, gasdermin D, IL-1β, IL-18, TNF-α and iNOS in microglia cultures treated with both IFN-γ and LPS were highest than with either one alone. Injecting IFN-γ into the lateral ventricle of mice induced similar morphological and functional changes in hippocampal microglia as in primary microglial cultures. The effects of IFN-γ on NLRP3 inflammasome and microglia from cultures or hippocampus were abolished when STAT1 was inhibited using fludarabin. Injecting mice with IFN-γ alone or together with LPS induced anxiety- and depression-like behaviors and impaired hippocampus-dependent spatial memory; these effects were mitigated by fludarabin. IFN-γ primes microglia by activating STAT1, which upregulates genes that activate the NLRP3 inflammasome. Inhibiting the IFN-γ/STAT1 axis may be a way to treat neurodegenerative diseases and psychiatric disorders that involve microglial priming.

A comprehensive study on mechanisms of action of fibroin, aloe vera, and ginger extracts through histochemical, inflammation biomarkers, and matrix metalloproteinases analysis against diabetic wounds

IntroductionDiabetes causes complications like delayed wound healing for a long time. Fibroin, aloe vera, and ginger extracts along with their combinations are used for diabetic wound healing. MethodsAfter induction of diabetes, The wound healing effects of fibroin (50 mg/ml), aloe vera gel (50 mg/ml), and ginger extract (30 mg/ml), individually and in combination, were assessed. The pro-inflammatory cytokines including tumor narcosis factor-α (TNF-α) interleukin (IL-6, IL-8, IL-1β), matrix metalloproteinases (MMP 2, MMP7, MMP 9), vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs) levels were analyzed in the serum. ResultsA combination of fibroin + aloe vera gel + ginger extract (Fi + Al + Gi) healed the wounds in 11 days via wound contraction of 98.5 ± 0.9 % as compared to diabetic control (58.2 ± 0.7 %) and positive control (73.3 ± 0.6 %) groups. However, the wounds of the Polyfax and the diabetic control groups were healed in 17 and 19 days, corresponding to a contraction of: 96.7 ± 1.4 % and 96.3 ± 1.1 %. The histological assay showed that the Fi + Al + Gi group indicated an increased growth of collagen fibers, fibroblasts, keratinocytes and blood vessels with lessened inflammation. The Fi + Al + Gi group alleviated the serum level of TNF-α (12.7 ± 0.9 pg/ml), IL-6 (9.6 ± 0.9 pg/ml), IL-8 (19.6 ± 1.0 pg/ml), MMP2 (217.0 ± 9.2 pg/ml), MMP7 (279.0 ± 9.8 pg/ml), and MMP9 (156.0 ± 11.6 pg/ml) significantly as compared to the diabetic control (P ≤ 0.05). TIMP serum level (202.0 ± 6.9 pg/ml) was significantly elevated as compared to the diabetes control group. ConclusionThe present study concludes that the biomaterials in their combinations possess high regenerative and healing abilities.

Ginsenoside Rb1 Alleviates DSS-Induced Ulcerative Colitis by Protecting the Intestinal Barrier Through the Signal Network of VDR, PPARγ and NF-κB.

Ginseng (Panax ginseng Meyer) is an herbal medicine used in traditional Chinese medicine (TCM), has the effects of treating colitis and other diseases. Ginsenoside Rb1 (GRb1), a major component of ginseng, modulates autoimmunity and metabolism. However, the mechanism underlying GRb1 treatment of ulcerative colitis (UC) has not yet been elucidated. UC is a refractory inflammatory bowel disease (IBD) with a high recurrence rate, and researches on new drugs for UC have been in the spotlight for a long time. Mice with DSS-induced UC were treated with GRb1 or 0.9% saline for 10 days. Colon tissue of UC mice was collected to detect the levels of intestinal inflammatory cytokines and integrity of the intestinal barrier. RNA-seq and network pharmacology were used to predict the therapeutic targets of GRb1 during UC treatment. GRb1 treatment alleviated intestinal inflammation and improved intestinal barrier dysfunction in UC mice. Specifically, GRb1 downregulated the levels of pro-inflammatory cytokines such as TNF-α and IL-6, while upregulating the level of the anti-inflammatory cytokine IL-10. Additionally, GRb1 treatment increased the levels of tight junction proteins including ZO-1, Occludin, and E-cadherin, which are crucial for maintaining intestinal barrier integrity. Further analyses using RNA-seq and network pharmacology suggested that these effects might involve the regulation of GRb1 in the signal transduction network of VDR, PPARγ, and NF-κB. The study demonstrated that GRb1 effectively alleviated UC by modulating intestinal inflammation and protecting the integrity of the intestinal barrier through the signal transduction network of VDR, PPARγ, and NF-κB.

Stilbene glycosides alleviate atherosclerosis partly by promoting lipophagy of dendritic cells

Atherosclerosis (AS) is a chronic inflammatory disease resulting from lipid metabolism disorders and immune imbalances. Dendritic cells (DCs) are key cells that regulate adaptive and adaptive immunity. When DCs engulf excessive amounts lipids, their function is altered, thereby, accelerating the inflammatory process of AS. Cellular lipophagy serves to reduce lipid accumulation and maintain cellular lipid metabolism balance. In this study, we investigated the effectiveness of 2,3,5,4′-tetrahydroxystilbene 2-O-β-D-glucoside (TSG) in intervening in the promotion of DCs lipid accumulation by ox-LDL, as well as its role in downregulating lipophagy. Our findings indicate that TSG reduces the maturity of DCs and promotes the differentiation of T cells towards Treg, thereby correcting the imbalanced Treg/Th17. These effects of TSG are closely associated with its inhibition of the PI3K-AKT-mTOR signaling pathway. After administering TSG to ApoE-/- mice that were fed a high-fat diet, there was a noticeable decrease in harmful blood lipids found in the serum. Additionally, the imbalanced Treg/Th17 levels in the spleen were restored, and the levels of pro-inflammatory factor IL-6 and IL-17A in the serum decreased, while the level of anti-inflammatory factor IL-10 increased. Furthermore, the arterial DCs showed a decrease in P62 content. Ultimately, these changes resulted in a reduction in plaque area. It is worth noting that the autophagy inhibitor chloroquine significantly altered the effects of TSG on ApoE-/- mice. In conclusion, this study reveals that TSG can alleviate AS. This is partly achieved through the activation of autophagy in DCs. By intervening in the lipophagy of DCs, it is possible to regulate the immune function of these cells, which in turn helps control the inflammation associated with AS. This presents a potential method for intervening in AS.

Flagellin conjugated Per a 10 and its T cell peptides attenuate airway inflammation and restore cellular function.

Adjuvants were used to modulate response towards relevant immune cells. The present study aims to investigate FlaA-conjugated Per a 10 and T cell peptides in amelioration of allergic airway disease in mice. Mice given Per a 10 showed allergic features with higher cellular infiltration, IgE, Th-2 cytokines and alarmins. Fusion protein treatment reduced lung inflammation (p < 0.0001) and cellular infiltrates (p < 0.001) with higher IgG2a/IgE indicating resolution of disease. Immunotherapy with FPT1 and FPT3 reduces IL-4, IL-5 and IL-13 levels (p < 0.0001) with a fourfold increase in IFN-γ secretion in BALF. FPT1- and FPT3-treated mice have increased IL-10 and TGF-β levels (p < 0.001) with CD4+Foxp3+ T cells (p < 0.01) indicating Treg response. There was enhanced expression of claudin-1 (1.7-fold) and occludin (fourfold) in lungs of FPT1- and FPT3-treated mice with reduced TSLP (p < 0.01) and IL-33 (p < 0.0001) secretion in BALF indicating recovery of epithelial function. Peptide-conjugated FlaA proteins showed protective immunity in mice and have potential for immunotherapy with restoration of cellular function.

Feeding Docosahexaenoic Acid and Arachidonic Acid during Suckling and Weaning Contributes to Oral Tolerance Development by Beneficially Modulating the Intestinal Cytokine and Immunoglobulin Levels in an Allergy-Prone Brown Norway Rat Model

BackgroundSuckling and weaning arachidonic acid (ARA) + docosahexaenoic acid (DHA) supplementation promoted oral tolerance (OT) development in pups, however, the effect of it on the intestine to promote OT development remains unknown. ObjectiveWe aimed to explore the impact of this supplementation on intestinal fatty acid composition, structure, and indicators that are supportive of OT development. MethodsAllergy-prone Brown Norway dams were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.45% ARA, 0.8% DHA) during suckling (0–3 wk). At weaning (3–8 wk), offspring were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.5% ARA, 0.5% DHA). At 3 wk, offspring in each group received an oral gavage of sucrose or ovalbumin (OVA) solution for five consecutive days. At 7 wk, all offspring received an intraperitoneal OVA injection. At 8 wk, offspring were terminated to evaluate jejunum morphology and measure mucosal food allergy-related secretory immunoglobulin A (sIgA) and cytokines, ileum phospholipid and triglyceride fatty acid compositions, and fecal calprotectin. ResultsWeaning ARA + DHA resulted in a higher percentage of DHA in ileum phospholipids and triglycerides (both P < 0.001), without affecting the percentage of ARA. Despite no lasting effect of suckling ARA + DHA on the DHA content in ileum phospholipids, a programming effect was found on the allergy-related intestinal immune profile [higher concentrations of mucosal IL-2 (P = 0.049) and sIgA (P = 0.033)]. OVA treatment resulted in a lower concentration of mucosal IL-6 (P = 0.026) regardless of dietary interventions. Offspring fed ARA + DHA during suckling and/or weaning had a higher concentration of mucosal transforming growth factor-beta (TGF-β) after OVA treatment but this was not observed in offspring fed control diets during suckling and weaning (P = 0.04). ConclusionsEarly life dietary ARA + DHA supplementation to allergy-prone rats enhanced the DHA concentration in intestinal phospholipids (weaning period) and increased the mucosal sIgA, IL-2, and TGF-β levels (suckling and weaning period), indicating its ability to create a tolerogenic intestinal environment to support OT development.

Effects of Amphotericin B-Conjugated Functionalized Carbon Nanoparticles in the Treatment of Cutaneous Leishmaniasis.

Leishmaniasis is a parasitic disease spread by the bite of an infected sandfly and caused by protozoan parasites of the genus Leishmania. Currently, there is no vaccine available for leishmaniasis in humans, and the existing chemotherapy methods face various clinical challenges. The majority of drugs are limited to a few toxic compounds, with some parasite strains developing resistance. Therefore, the discovery and development of a new anti-leishmanial compound is crucial. One promising strategy involves the use of nanoparticle delivery systems to accelerate the effectiveness of existing treatments. In this study, Amphotericin B (AmB) was incorporated into functionalized carbon nanotube (f-CNT) and evaluated for its efficacy against Leishmania major in vitro and in a BALB/c mice model. The increase in footpad thickness was measured, and real-time PCR was used to quantify the parasite load post-infection. Levels of nitric oxide and cytokines IL-4 and IFN-γ were also determined. We found that f-CNT-AmB significantly reduced the levels of promastigotes and amastigotes of the Leishmania parasite. The nanoparticle showed strong anti-leishmanial activity with an IC50 of 0.00494 ± 0.00095 mg/mL for promastigotes and EC50 of 0.00294 ± 0.00065 mg/mL for amastigotes at 72 h post-infection, without causing harm to mice macrophages. Treatment of infected BALB/c mice with f-CNT-AmB resulted in a significant decrease in cutaneous leishmania (CL) lesion size in the foot pad, as well as reduced Leishmania burden in both lymph nodes and spleen. The levels of nitric oxide and IFN-γ significantly increased in the f-CNT-AmB treated groups. Also, our results showed that the level of IL-4 significantly decreased after f-CNT-AmB treatment in comparison to other groups. In conclusion, our results demonstrate that AmB loaded into f-CNT is significantly more effective than AmB alone in inhibiting parasite propagation and promoting a shift towards a Th1 response.

Correlations of gray matter volume with peripheral cytokines in Parkinson's disease

IntroductionPeripheral cytokine levels may affect specific brain volumes. Few studies have examined this possible relationship. ObjectiveIn a case–control study, we used magnetic resonance imaging (MRI) voxel-based morphological analysis techniques to examine the relationship between gray matter volume changes and cognitive, motor and emotional dysfunction as well as between gray matter volume changes and peripheral blood cytokine levels. MethodA total of 134 subjects, comprising 66 PD patients and 68 healthy controls, were recruited. Peripheral venous blood was collected to measure the concentrations of 12 cytokines, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-α, IFN-γ, and TNF-α. All the subjects also underwent MRI, where 3D-T1-weighted MR images were used for the analysis. In addition, the Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE), Unified Parkinson's disease Rating Scale (UPDRS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were assessed in PD patients. Statistical parameter mapping 12 software was used for the statistical analysis of the images. ResultCompared with control patients, PD patients presented decreased gray matter volume (GMV) in the bilateral frontal lobe, temporal lobe, parietal lobe, occipital lobe, insula, and right cerebellar lobule VIII. Regional GMV in the temporal lobe, parietal lobe, and cerebellum was correlated with MoCA, MMSE, UPDRS, HAMA, and HAMD scores in PDs. In addition, the regional GMV in PDs was correlated with the concentrations of cytokines, including IL-4, IL-6, IFN-γ, and TNF-α. The IL-6 concentration was negatively correlated with the UPDRS-IV score. ConclusionPD patients exhibit gray matter atrophy in a wide range of brain regions, which are symmetrically distributed and mainly concentrated in the frontal and temporal lobes, and these changes may be linked to motor disorders and neuropsychiatric manifestations. Cytokine concentrations in peripheral blood are correlated with regional gray matter volume in PDs, and the IL-6 level affects gray matter volume in the left precentral gyrus and the manifestation of motor complications.

Almond polysaccharides inhibit DSS-induced inflammatory response in ulcerative colitis mice through NF-κB pathway

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic recurrent inflammatory disease of the colon. Our previous findings demonstrated that almond polysaccharide (AP-1) exhibits significant anti-inflammatory activity in vitro. Therefore, this study aimed to explore the ameliorative effect of AP-1 on dextrose sodium sulfate (DSS)-induced UC mice and to elucidate its possible mechanism of action. By observing changes in body weight, fecal viscosity, stool blood, disease activity index, and colon length, we found that AP-1 attenuated inflammation. It inhibited TNF-α, IL-1β, and IL-6 while boosting anti-inflammatory IL-10 levels. Histomorphologically, AP-1 protected against DSS-induced colonic tissue damage by reducing inflammatory cell infiltration and mucosal injury. It also lowered myeloperoxidase (MPO) and NO while increasing total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in colonic tissues. Moreover, using the Western blot technique, AP-1 was shown to inhibit the phosphorylation of p65 and IκB-α proteins in the NF-κB/iNOS/COX2 signaling pathway and down-regulate the expression of inflammation-associated proteins COX2 and iNOS, thus slowing down and ameliorating inflammatory processes. Therefore, the safe and effective beneficial effects of AP-1 make it a promising therapeutic strategy for relieving IBD, especially UC.

Assessment IL-6, TGF-1, CRP, and Vit-D in Women With Uterine Fibroid

Background: Uterine fibroids, also known as UFs, are the most common type of tumor that occurs in the female reproductive system. They affect a significant majority, around 70-80%, of women during their lifetime. Various factors that increase the incidence of Uterine Fibroids (UFs) have been found, including as vitamin D deficiency, inflammation, DNA repair deficit, and exposure to endocrine-disrupting chemicals (EDCs) in the environment. Objective: The purpose of this study to evaluated the level of IL-6, TGF-1, CRP, and Vit-D in women with uterine fibroid and study the relation these parameter with different ages. Materials and methods: 90 blood samples were collected and divided into (50) blood samples from women with uterine fibroids who received a diagnosis from a qualified medical specialist, and (40) blood samples from healthy women, whose ages ranged from (20-50). Assessment level of IL-6, TGF-1, CRP, and Vit-D have been done by using ELISA technique. Result: The results showed that there was no significant difference at the probability level (P&gt;0.05) in the level of IL-6 in women with uterine fibroids, as it reached (44.9±4.4 pg/ml) when compared with healthy women (42.5±4.1 pg/ml). The results of this study showed a significant increase in the levels of both β-TGF and CRP in women with uterine fibroids at the probability level (P&lt;0.05), reaching (2.870±0.760ng/ml, 62.9±6.4 pg/ml), respectively, when compared with Healthy women: As for Vit.D3, it showed a significant decrease in women with uterine fibroids at the probability level (P≤0.05), as it reached (5.92±1.87 ng/ml). Conclusion: This result concluded no differences in the level of IL-6 in women with uterine fibroids, while increase in the levels of both β-TGF and CRP . Furthermore, decrease level of Vit.D3.