Can supplementation of tryptophan in parenteral nutrition increase melatonin and alleviate inflammatory response?

OBJECTIVE: Endogenous melatonin is produced from tryptophan which is an essential amino acid. Besides its role in the regulation of sleep patterns, melatonin has anti-inflammatory effects. In this case-control study, we aimed to compare tryptophan and melatonin levels and their relationship with the inflammatory response, specifically serum interleukin-1, interleukin-6, and c-reactive protein levels following major abdominal surgery in patients with food restriction and who receive parenteral nutritional therapy. METHODS: We enrolled 40 patients between the ages of 18 and 65 years in the study. We collected blood and urine samples 48 h before the operation and on postoperative days 1, 3, and 5. RESULTS AND CONCLUSION: The tryptophan levels in the experimental group were higher than in the control group but failed to reach any statistical difference. Melatonin levels were increased in both groups following the surgery compared with preoperative levels. The increase in the experimental group was statistically different 3 days after the surgery. The difference in the level of interleukin-1 between the control and the experimental groups was greatest on postoperative day 3. On postoperative day 3, the interleukin-6 level in the treatment group was slightly higher than in the control group. We did not find any difference in the levels of c-reactive protein between the groups. As a result, the levels of tryptophan and melatonin were increased in the parenteral nutrition group, irrespective of the postoperative inflammatory response.

Effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological profiles during transition period in dromedary camels.

BACKGROUND: Nutrition has a primary role for optimum expression of genetic potential, and most of the farmers have limited resources of green fodder. Hence, a fat-soluble vitamin, especially vitamin A and E and trace elements remained most critical in the animal's ration and affects their productive and reproductive performance adversely. Animals cannot be able to produce these vitamins in their bodies; hence, an exogenous regular supply is needed to fulfil the physiological needs and to maintain high production performance. This study elucidated effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological parameters in dromedary camels during transition period. RESULTS: At 0 day, there were no appreciable differences in the expression patterns of the metabolic (IGF-I, ACACA, SCD, FASN, LPL, and BTN1A1) genes between the control and treatment groups, despite lower levels. A substantial variation in the mRNA levels of SOD1, SOD3, PRDX2, PRDX3, PRDX4, PRDX6, and AhpC/TSA was observed between the control and treatment groups, according to the antioxidant markers. In comparison to the control group, the treatment group displayed a significant up-regulation at 0 and 21 days. The treatment and control groups exhibited substantial differences in the mRNA values of IL-1α, IL-1ß, IL-6, and TNFα, as indicated by immunological markers. In comparison to the control group, there was a noticeable down-regulation in the treatment group at 0 and + 21 days. But IL10 produced the opposite pattern. No significant difference was observed in glucose, cholesterol, triglyceride, HDL, total protein, NEFA, BHBA, cortisol and IGF-1 levels between control and treatment group. The activity of serum GPx, SOD and TAC was significantly affected by time and treatment x time in supplemented groups as compared with control group. IL-1, IL-1, IL-6, and TNF were noticeably greater in the control group and lower in the treatment group. Additionally, in all groups, the concentration of all pro-inflammatory cytokines peaked on the day of delivery and its lowest levels showed on day 21 following calving. The IL-10 level was at its peak 21 days prior to calving and was lowest on calving day. CONCLUSION: The results demonstrated a beneficial effect of antioxidant vitamins and trace elements on the metabolic, antioxidant and immunological markers in dromedary camels throughout their transition period.

Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis.

OBJECTIVE: Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. METHODS: Mice received 0.1 mg/25µL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 µL or saline per os (systemic) or 500 µg/25 µL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. RESULTS: MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. CONCLUSION: MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

The immune enhancing effect of antimicrobial peptide LLv on broilers chickens.

To evaluate the effect and its mechanism of heat-resistant antimicrobial peptide LLv on broilers, three hundred 1-day-old healthy AA+ female broilers were allocated into 5 groups with 6 replicates in each group and 10 birds in each replicate. Birds were given a basal diet, an antibiotic diet (10.2 mg/kg chlortetracycline hydrochloride), and the basal diet supplemented with 10, 50, and 100 mg/kg LLv for 42 d, respectively. Compared with the group which birds were fed an antibiotic-free basal diet (control group), supplementing 100 mg/kg LLv increased 21-day IgA, IgM, IL-4, AIV-Ab, IFN-γ levels and 42-day IgA, IgM, IL-4, AIV-Ab levels and reduced 42-day IL-1 levels in serum (P < 0.05). Compared with antibiotic group, the 10 and 50 mg/kg LLv decreased 42-day IgM levels in serum (P < 0.05). The 100 mg/kg LLv increased 21-day AIV-Ab levels and 42-day IL-4, AIV-Ab levels and reduced 42-day IL-1 levels in serum (P < 0.05). Compared with control group, the 100 mg/kg LLv increased the expression rate of sIgA secretory cells and sIgA content in jejunal mucosa at 21 d and 42 d (P < 0.05), which did not differ from antibiotic group (P > 0.05). Compared with antibiotic group, the 10 mg/kg LLv reduced 21-day sIgA content and the 50 mg/kg LLv reduced 42-d the expression rate of sIgA secretory cells in jejunal mucosa (P < 0.05). Compared with control group, the 100 mg/kg LLv increased the expression of TCR, IL-15, CD28, BAFF, CD86, CD83, MHC-II, and CD40 genes in jejunal mucosa at 21 d and 42 d (P < 0.05). Compared with antibiotic group, the 100 mg/kg LLv increased the expression of 21-day BAFF, CD40, MHC-II, CD83 genes and the expression of 42-day BAFF, TCR, IL-15, CD40, CD83 genes in jejunal mucosa (P < 0.05). The results showed that the addition of LLv to the ration had a promotional effect on the immune function of broiler chickens.

The therapeutic effect of wine-processed Corni Fructus on chronic renal failure in rats through the interference with the LPS/IL-1-mediated inhibition of RXR function.

ETHNOPHARMACOLOGICAL RELEVANCE: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus. Generally, TCM is often used after processing (paozhi). Despite the extensive use of processed TCM, the underlying mechanisms of processing for most TCMs have been unclear so far. AIM OF THE STUDY: In this study, an integrated strategy combined renal metabolomics with proteomics was established and investigated the potential processing mechanisms of CCF or WCF on chronic renal failure (CRF) models. MATERIALS AND METHODS: Firstly, the differences in biochemical parameters and pathological histology were compared to evaluate the effects of CCF and WCF on CRF model rats. Then, the tissue differential metabolites and proteins between CCF and WCF on CRF model rats were screened based on metabolomics and proteomics technology. Concurrently, a combined approach of metabolomics and proteomics was employed to investigate the underlying mechanisms associated with these marker metabolic products and proteins. RESULTS: Compared to the MG group, there were 27 distinct metabolites and 143 different proteins observed in the CCF-treatment group, while the WCF-treatment group exhibited 24 distinct metabolites and 379 different proteins. Further, the integration interactions analysis of the protein and lipid metabolite revealed that both WCF and CCF improved tryptophan degradation and LPS/IL-1-mediated inhibition of RXR function. WCF inhibited RXR function more than CCF via the modulation of LPS/IL-1 in the CRF model. Experimental results were validated by qRT-PCR and western blotting. Notably, the gene expression amount and protein levels of FMO3 and CYP2E1 among 8 genes influenced by WCF were higher compared to CCF. CONCLUSION: The results of this study provide a theoretical basis for further study of Corni Fructus with different processing techniques in CRF. The findings also offer guidance for investigating the mechanism of action of herbal medicines in diseases employing diverse processing techniques.

Andrographolide Attenuates Oxidized LDL-Induced Activation of the NLRP3 Inflammasome in Bone Marrow-Derived Macrophages and Mitigates HFCCD-Induced Atherosclerosis in Mice.

Andrographolide (AND) is a bioactive component of the herb Andrographis paniculata and a well-known anti-inflammatory agent. Atherosclerosis is a chronic inflammatory disease of the vasculature, and oxidized LDL (oxLDL) is thought to contribute heavily to atherosclerosis-associated inflammation. The aim of this study was to investigate whether AND mitigates oxLDL-mediated foam cell formation and diet-induced atherosclerosis (in mice fed a high-fat, high-cholesterol, high-cholic acid [HFCCD] diet) and the underlying mechanisms involved. AND attenuated LPS/oxLDL-mediated foam cell formation, IL-1[Formula: see text] mRNA and protein (p37) expression, NLR family pyrin domain containing 3 (NLRP3) mRNA and protein expression, caspase-1 (p20) protein expression, and IL-1[Formula: see text] release in BMDMs. Treatment with oxLDL significantly induced protein and mRNA expression of CD36, lectin-like oxLDL receptor-1 (LOX-1), and scavenger receptor type A (SR-A), whereas pretreatment with AND significantly inhibited protein and mRNA expression of SR-A only. Treatment with oxLDL significantly induced ROS generation and Dil-oxLDL uptake; however, pretreatment with AND alleviated oxLDL-induced ROS generation and Dil-oxLDL uptake. HFCCD feeding significantly increased aortic lipid accumulation, ICAM-1 expression, and IL-1[Formula: see text] mRNA expression, as well as blood levels of glutamic pyruvic transaminase (GPT), total cholesterol, and LDL-C. AND co-administration mitigated aortic lipid accumulation, the protein expression of ICAM-1, mRNA expression of IL-1[Formula: see text] and ICAM-1, and blood levels of GPT. These results suggest that the working mechanisms by which AND mitigates atherosclerosis involve the inhibition of foam cell formation and NLRP3 inflammasome-dependent vascular inflammation as evidenced by decreased SR-A expression and IL-1[Formula: see text] release, respectively.

Matrine From Sophora Flavescens Attenuates on Collagen-Induced Osteoarthritis by Modulating the Activity of miR-29B-3P/PGRN Axis.

Matrine is an active ingredient in traditional Chinese medicine that has been shown to be effective in treating bone disorders. The anti-osteoarthritis (OA) effects of matrine were assessed using both in in vitro and in vivo systems, and the mechanisms underlying the effects were investigated by focusing on the activity of miR-29b-3p/PGRN axis. The miR was chosen as potential target for matrine after chondrocytes were treated with both IL-1? and matrine. Changes in cell viability, cell apoptosis, inflammation, and miR-29b-3p/PGRN axis were detected. In vitro assays results were validated using collagen-induced arthritis (CIA) rat models. Incubation with IL-1? reduced cell viability, induced cell apoptosis, and inhibited production of cytokines in chondrocytes, which was associated with the up-regulation of miR-29b-3p and down-regulation of PGRN. In CIA rats, matrine reduced bone destruction and weight loss in a dose-dependent manner. Matrine also reduced the systemic levels of cytokines. At the molecular level, matrine inhibited the expression of miR-29b-3p while increasing the expression of PGRN. The findings outlined in the current study showed that matrine exerted its anti-OA effects by modulating the miR-29b-3p/PGRN axis.

Pachymic Acid Prevents Hemorrhagic Shock-Induced Cardiac Injury by Suppressing M1 Macrophage Polarization and NF-[Formula: see text]B Signaling Pathway.

Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos, has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15[Formula: see text]mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1[Formula: see text], IL-6, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86[Formula: see text]) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206[Formula: see text]) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF-[Formula: see text]B pathway activation via inhibiting NF-[Formula: see text]B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF-[Formula: see text]B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.

Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained by the higher blood levels of pro-inflammatory hormones and cytokines, such as melatonin, TNFα, IL-1, and IL-6, in the early morning than in the afternoon as well as insufficient levels of anti-inflammatory cortisol, which rises later in the morning. Clinical importance of the circadian regulation of RA symptoms has been demonstrated by the effectiveness of time-of-day-dependent delivery of therapeutic agents in chronotherapy. The primary inflammatory site in RA is the synovium, where increased macrophages, T cells, and synovial fibroblasts play central roles by secreting pro-inflammatory cytokines, chemokines, and enzymes to stimulate each other, additional immune cells, and osteoclasts, ultimately leading to cartilage and bone erosion. Among these central players, macrophages have been one of the prime targets for the study of the link between circadian rhythms and inflammatory activities. Gene knockout experiments of various core circadian regulators have established that disruption of any core circadian regulators results in hyper- or hypoactivation of inflammatory responses by macrophages when challenged by lipopolysaccharide and bacteria. Although these stimulations are not directly linked to RA etiology, these findings serve as a foundation for further study by providing proof of principle. On the other hand, circadian regulation of osteoclasts, downstream effectors of macrophages, remain under-explored. Nonetheless, circadian expression of the inducers of osteoclastogenesis, such as TNFα, IL-1, and IL-6, as well as the knockout phenotypes of circadian regulators in osteoclasts suggest the significance of the circadian control of osteoclast activity in the pathogenesis of RA. More detailed mechanistic understanding of the circadian regulation of macrophages and osteoclasts in the afflicted joints could add novel local therapeutic options for RA.

Long-term in vivo vitamin D3 supplementation modulates bovine IL-1 and chemokine responses.

Vitamin D deficiency at birth, followed by prolonged insufficiency in early life may predispose bovine calves to infection and disease. However, the effects of vitamin D levels on innate immunity are unclear due to the lack of long-term supplementation trials in vivo and reliable approaches for reproducibly assessing immune function. Here, a standardized whole blood immunophenotyping assay was used to compare innate immune responses to infection relevant ligands (LPS, Pam3CSK4 and R848) between Holstein-Friesian calves supplemented with vitamin D (n = 12) from birth until 7 months of age and control calves (n = 10) raised on an industry standard diet. Transcriptomic analysis in unstimulated whole blood cells revealed increased expression of type I interferons and chemokines in vitamin D supplemented calves, while IL-1 and inflammasome gene expression was decreased. In response to stimulation with the bacterial ligand LPS, supplemented calves had significantly increased expression of CASP1, CX3CR1, CAT, whereas STAT1 was decreased. Stimulation with the bacterial ligand Pam3CSK4 revealed increased expression of IL1A, IL1B and CAT genes; and decreased C5AR1 expression. In response to the viral ligand R848, STAT1 and S100A8 expression was significantly decreased. An increased IL-1 and inflammasome gene expression signature in vitamin D supplemented calves in response to LPS and Pam3CSK4 was also found, with ELISA confirming increased IL-1ß protein production. In contrast, a decreased chemokine gene expression signature was found in response to R848 in supplemented animals, with decreased IL-8 protein expression exhibited in response to all PAMPs also found. These results demonstrated expression of several cytokine, chemokine and inflammasome genes were impacted by vitamin D supplementation in the first 7 months of life, with IL-8 expression particularly responsive to vitamin D. Overall, vitamin D supplementation induced differential innate immune responses of blood immune cells that could have important implications for disease susceptibility in cattle.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Uncovering tomato candidate genes associated with drought tolerance using Solanum pennellii introgression lines.

Tomato plants are sensitive to drought stress throughout their growth cycle. To be considered drought-tolerant, a cultivar should display tolerance at all developmental stages. This study aimed to evaluate whether Solanum pennellii introgression lines (ILs) previously selected as drought-tolerant during germination/seedling growth maintained this tolerance in the vegetative/reproductive stage. We then investigated these ILs to uncover candidate genes. The plants were subjected to two different environmental conditions: well-watered and drought-stressed (water withheld for ≤ 20 d after flowering). Phenotyping for morphological, physiological, fruit quality, and yield-related traits was performed, and the data was analyzed using a mixed-model approach. Using a multi-trait index that relies on factor analysis and genotype-ideotype distance (FAI-BLUP index), the genotypes were ordered based on how far they were from the drought-tolerant ideotype. Afterward, the tomato IL population map furnished by the SOL Genomics Network was utilized to identify introgressed segments of significance for the identification of candidate genes. Significant genotypic differences were found in the yield, water content, mean weight, length, and width of the fruit, the percentage of fruits displaying blossom-end rot, and titratable acidity. The drought-tolerance ideotype was built considering the maximum values for the fruit water content, number of fruits, mean fruit weight, and yield, minimum values for blossom-end rot, and mean values for titratable acidity. IL 1-4-18, IL 7-4-1, IL 7-1, IL 7-5-5, and IL 1-2 were ranked above M-82 and therefore considered drought-tolerant during the vegetative/reproductive stage. IL 1-4-18 and IL1-2 sustained drought tolerance displayed during germination/seedling growth into the vegetative/reproductive stage. The following candidate genes associated with drought tolerance were identified: AHG2, At1g55840, PRXIIF, SAP5, REF4-RELATED 1, PRXQ, CFS1, LCD, CCD1, and SCS. Because they are already associated with genetic markers, they can be transferred to elite tomato cultivars through marker-assisted technology after validation.

Effects of Traditional Chinese Medicine on Serum Cytokines for the Dampness-heat Syndrome of Ulcerative Colitis: A Systematic Review and Meta-analysis.

Context: Ulcerative colitis (UC) is a chronic disease affecting the large intestine. Cytokines, as inflammatory mediators, can enable pathological injury of the intestinal mucosa and play an important role in UC's pathogenesis. Traditional Chinese medicine (TCM) offers a wealth of theory and experience in UC's treatment. Objective: The literature review and meta-analysis intended to examine TCM's effects in the treatment of UC patients who have the dampness-heat syndrome on the serum cytokines known to be related to UC's pathogenesis. Design: The research team conducted a comprehensive literature search for randomized controlled trials (RCTs) in seven databases. The search covered all publicly published documents from the establishment of a database until August 31, 2021. The team also performed a meta-analysis of the RCTs' results to compare the levels of cytokines in the intervention and control groups. Setting: The study took place at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University of Traditional Chinese Medicine in Shanghai, China. Interventions: For the meta-analysis, the research team created two intervention groups, the oral TCM only group and the TCM+ Western Medicine (WM) group and a control group, the WM group. The team determined which RCT's measured a particular cytokine and which groups those RCTs compared, the team examined the differences between the groups postintervention. Outcome Measures: The primary outcome measures were the RCTs' levels of 13 serum cytokines-interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), IL-17, IL-23, interferon-gamma (IFN-γ), IL-21, IL-1, IL-1ß, IL-2, IL-4, IL-10, and IL-13. The team used the random effects model to combine the results for the serum markers as standardized mean differences (SMDs) and compared the two intervention groups to the control group. Results: The research team identified 22 studies that included 1957 participants. The team found that six proinflammatory cytokines were significantly lower in the combined TCM only and TCM+WM intervention groups than in the WM control group: (1) IL-6-SMD -2.60, 95%CI -3.37 to -1.83, P < .00001; (2) IL-8-SMD -2.49, 95%CI -3.34 to -1.64, P < .00001; (3) TNF-α-SMD -1.70, 95%CI -2.07 to -1.33, P < .00001; (4) IL-17 (TCM+WM group only)-SMD-2.99, 95%CI -4.66 to -1.31, P = .0005; (5) IL-23 (TCM+WM group only)-SMD -2.43, 95% CI -2.78 to -2.08, P < .00001; and (6) IFN-γ-SMD -1.47, 95% CI -1.81 to -1.12, P < .00001. The team found that two anti-inflammatory cytokines were significantly higher in the intervention group than in the control group: (1) IL-4-SMD 1.45, 95% CI 0.92-1.99, P < .00001, and (2) IL-10-SMD 1.33, 95% CI 0.97-1.69, P < .00001. For the results that the team couldn't combine, the levels of the proinflammatory cytokines IL-1, IL-1ß, IL-2, and IL-21 were significantly lower in the combined intervention groups than in the control group (P < .05), and the level of the anti-inflammatory cytokine IL-13 in the intervention group was significantly higher than that in the control group (P < .05). The comprehensive analysis showed that oral TCM or a combination of TCM and WM could more significantly reduce the levels of the proinflammatory cytokines IL-6, IL-8, TNF-α, IL-17, IL-23, IFN-γ, IL-21, IL-1, IL-1ß and IL-2 and increase the levels of the anti-inflammatory cytokines IL-4, IL-10 and IL-13. Conclusions: Oral TCM or TCM+WM can reduce the proinflammatory response and increase the anti-inflammatory response of UC patients by regulating serum cytokines and can obtain a better clinical effect than WM only. These benefits can alleviate intestinal inflammation in patients and have a positive effect on clinical efficacy. In the future, more high-quality, large-sample, and long-term follow-up randomized controlled trial are necessary to support research analysis.

In vitro and in vivo assessment of the anti-inflammatory activity of olive leaf extract in rats.

Inflammation is a complex and crucial process that protects the body against pathogens. Here in our study, we propose to scientifically justify the anti-inflammatory activity of olive leaf (OL). Initially, we ensured the safety of olive leaf extract (OLE) through acute oral administration of graded doses up to 4 g\kg in Wistar rats. Thus, the extract was considered generally safe. We also evaluated the ability of the extract to reduce carrageenan-induced rat paw edema. Compared to diclofenac sodium (10 mg/kg PO), OLE showed significant (P < 0.05) anti-inflammatory activity, showing the maximum inhibition percentage at the fifth hour of measurement at 42.31% and 46.99%, at doses of 200 and 400 m/kg, respectively, compared to 63.81% for the standard drug. To elucidate the potential mechanism, we measured TNF, IL-1, COX-2 and NO inside the paw tissue. Interestingly, OLE at all tested doses reduced the concentration of TNF and IL-1 to a level that was lower than that obtained by the standard drug. Additionally, OLE at the dose of 400 mg/kg reduced the levels of COX-2 and NO inside the paw tissue to a level that was statistically equivalent to the level observed in the normal control group. Finally, olive leaf extract at doses of 100, 200 and 400 mg/kg doses significantly (P < 0.05) inhibited the heat-induced hemolysis of RBCs membrane by 25.62, 57.40 and 73.88%, respectively, compared to 83.89% produced by aspirin. Consequently, we concluded that olive leaf extract has a significant anti-inflammatory activity through the reduction of TNF, IL-1, COX-2 and NO.

[Effect of moxibustion on the indicators of autophagy and apoptosis in synovium of rats with adjuvant arthritis].

OBJECTIVE: To observe the effect of moxibustion on the indicators of autophagy and apoptosis in the synovium of toes of rats with adjuvant-induced arthritis (AA), so as to explore the underlying mechanism of moxibustion in the treatment of rheumatoid arthritis. METHODS: Forty-five SD rats were randomly divided into the blank control group, model group, moxibustion group, methotrexate group and rapamycin group, with 9 rats in each group. The rat model of AA was established by injecting Freund's complete adjuvant. Rats in the moxibustion group received moxibustion treatment at "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, once a day. The methotrexate group was given methotrexate intragastrically (0.35 mg/kg) twice a week. The rapamycin group was given rapamycin by intraperitoneal injection (1 mg/kg), once every other day. The toe volume of the left hind limb was measured by the toe volume measuring instrument after 3-day modeling and 3-week intervention respectively. The contents of interlukin(IL)-1 and tumor necrosis factor(TNF)-α in serum were detected by ELISA. The autophagosomes of synovial cells of the toe joint were observed under transmission electron microscope. The expressions of mammalian target of rapamycin(mTOR)C1, p-mTORC1, Caspase-3, Fas and FasL in synovial tissue were detected by Western blot. RESULTS: Under transmission electron microscope, the model group showed decreased autophagosomes in synovial tissues, but the moxibustion, methotrexate, and rapamycin groups showed increased autophagosomes. Compared with the blank control group, the toe volume, the contents of IL-1 and TNF-α in serum and the expression of p-mTORC1 protein in synovial tissue were significantly increased (P<0.01, P<0.001), while the expressions of Caspase-3, Fas and FasL proteins in synovial tissue were significantly decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the toe volume, the contents of IL-1 and TNF-α in the serum, and expression of p-mTORC1 protein were significantly decreased (P<0.05, P<0.01, P<0.001) in the moxibustion group and the methotrexate group, while the expression of Caspase-3, Fas and FasL proteins in synovial tissue in the moxibustion group and the methotrexate group, the expression of Caspase-3 in the rapamycin group were significantly increased (P<0.05). CONCLUSION: Moxibustion can improve joint swelling in AA rats and decrease the contents of serum IL-1 and TNF-α. The mechanism may be related to regulating the expressions of p-mTORC1, Caspase-3, Fas and FasL proteins, and promoting autophagy and apoptosis of synovial cells.

New Data on Anti-Inflammatory and Wound Healing Potential of Transgenic Senna obtusifolia Hairy Roots: In Vitro Studies.

Asthma is an inflammatory disease whose etiology remains unclear. Its characteristics encompass a wide range of clinical symptoms, inflammatory processes, and reactions to standard therapies. Plants produce a range of constitutive products and secondary metabolites that may have therapeutic abilities. The aim of this study was to determine the effects of Senna obtusifolia transgenic hairy root extracts on virus-induced airway remodeling conditions. Three cell lines were incubated with extracts from transformed (SOA4) and transgenic (SOPSS2, with overexpression of the gene encoding squalene synthase 1) hairy roots of Senna obtusifolia in cell lines undergoing human rhinovirus-16 (HRV-16) infection. The effects of the extracts on the inflammatory process were determined based on the expression of inflammatory cytokines (IL-8, TNF-α, IL-1α and IFN-γ) and total thiol content. The transgenic Senna obtusifolia root extract reduced virus-induced expression of TNF, IL-8 and IL-1 in WI-38 and NHBE cells. The SOPSS2 extract reduced IL-1 expression only in lung epithelial cells. Both tested extracts significantly increased the concentration of thiol groups in epithelial lung cells. In addition, the SOPPS2 hairy root extract yielded a positive result in the scratch test. SOA4 and SOPPS2 Senna obtusifolia hairy root extracts demonstrated anti-inflammatory effects or wound healing activity. The SOPSS2 extract had stronger biological properties, which may result from a higher content of bioactive secondary metabolites.

Assessment of anti-inflammatory efficacy of acupuncture in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: Inflammation has a significant role in the onset and progression of inflammatory bowel disease (IBD). Increasing attention has been paid to the use of acupuncture in IBD patients; however, its regulatory effects on inflammatory factors in IBD still require validation. Here, we systematically evaluated the effects of acupuncture on inflammatory factors in IBD patients. METHODS: Eight electronic databases were searched for studies that met the inclusion criteria. After evaluating the quality of the studies selected by two reviewers, the meta-analysis was performed to assess the efficacy of acupuncture in IBD patients and the impact on inflammatory factors (TNF-α, IL-1, IL-8 and IL-10). RESULTS: Four randomized controlled trials with a total of 228 patients satisfied the inclusion criteria. Acupuncture has a positive therapeutic impact on IBD (MD = 1.22, 95% CI [1.07, 1.39], P = 0.003). Moreover, it regulates the levels of TNF-α (MD =-60.58, 95% CI [-100.30, -20.89], P = 0.003), IL-8 (MD =-56.40, 95% CI [-60.02, -52.14], P < 0.00001) and IL-10 (MD =35.96, 95% CI [11.02, 60.91], P = 0.005) in IBD patients. However, the P value of meta-analysis in IL-1 great than 0.05.(MD =-27.90, 95% CI [-97.82, 42.02], P = 0.11). CONCLUSION: Acupuncture has a positive therapeutic impact on IBD and can effectively regulate inflammatory factors in IBD patients. TNF-α, IL-8 and IL-10 are more appropriate inflammatory indicators for clinically evaluating the anti-inflammatory response in the blood of IBD patients by acupuncture.

IL-1/MyD88-Dependent G-CSF and IL-6 Secretion Mediates Postburn Anemia.

The anemia of critical illness (ACI) is a nearly universal pathophysiological consequence of burn injury and a primary reason burn patients require massive quantities of transfused blood. Inflammatory processes are expected to drive postburn ACI and prevent meaningful erythropoietic stimulation through iron or erythropoietin supplementation, but to this day no specific inflammatory pathways have been identified as a critical mechanism. In this study, we examined whether secretion of G-CSF and IL-6 mediates distinct features of postburn ACI and interrogated inflammatory mechanisms that could be responsible for their secretion. Our analysis of mouse and human skin samples identified the burn wound as a primary source of G-CSF and IL-6 secretion. We show that G-CSF and IL-6 are secreted independently through an IL-1/MyD88-dependent mechanism, and we ruled out TLR2 and TLR4 as critical receptors. Our results indicate that IL-1/MyD88-dependent G-CSF secretion plays a key role in impairing medullary erythropoiesis and IL-6 secretion plays a key role in limiting the access of erythroid cells to iron. Importantly, we found that IL-1α/ß neutralizing Abs broadly attenuated features of postburn ACI that could be attributed to G-CSF or IL-6 secretion and rescued deficits of circulating RBC counts, hemoglobin, and hematocrit caused by burn injury. We conclude that wound-based IL-1/MyD88 signaling mediates postburn ACI through induction of G-CSF and IL-6 secretion.

Immunomodulatory effects of graded levels of docosahexaenoic acid (DHA) in common carp (Cyprinus carpio) - In vitro and in vivo approaches.

The D-series resolvins formed from docosahexaenoic acid (DHA) work as anti-inflammatory mediators indicating the role of this long-chain polyunsaturated fatty acid in the immune system of mammals. However, such information is still limited in fish. The current study was conducted to evaluate the immunomodulatory effects of graded levels of DHA in common carp Cyprinus carpio by in vitro and in vivo approaches. In the in vitro experiment, the head kidney leukocytes isolated from common carp (body weight = 120.3 ± 12.4 g) were exposed to DHA at 0, 15, and 75 µM (corresponding to DHA0, DHA15, and DHA75) for 1 h; the cells were then immediately exposed to lipopolysaccharides (LPS) at a dose of 10 µg/ml for 4 or 24 h to stimulate the pro-inflammatory responses. The expression of several target genes involved in the inflammatory response (tlr4, nfkb, il-1, il-6, pge2, pla2, nf-kbi, il-10, and tgf-ß1) and cytoprotection (hsp70, gpx1, and prdx3) was then assessed by RT-qPCR. Results showed that the pro-inflammatory response induced by LPS was confirmed through the upregulations of il-1 and il-6 expressions in the DHA0 group after 4 h of LPS exposure. The downregulations of il-6 in DHA15 and DHA75 cells after 4 h of LPS exposure compared to DHA0 indicated that the free DHA supplementation in the cell culture medium induced an anti-inflammatory response. Decreases of il-10 and nf-kbi expression were also observed in DHA-treated groups and the highest expression of hsp70 in DHA75 cells. In the in vivo experiment, common carp juveniles (21.7 ± 0.9 g) were fed to apparent satiation with a diet supplemented with DHA at 0, 6, and 20 g/kg for 8 weeks. After the feeding trial, the fish were challenged with Aeromonas veronii at 2.1 × 107 CFU/ml and the fish mortality was then recorded during 14 days. At the end of the feeding trial and the second day of bacterial infection, fish blood samples were collected for haematological parameters while liver and head kidney were used for assaying different immune variables. Results showed that the DHA supplementation in fish diet did not influence the fish growth and other husbandry parameters. The lowest value of fish mortality was recorded in DHA20-fed fish. The positive effects of DHA-supplemented diets were also found in myeloperoxidase (MPO), glutathione (GSH), and catalase (CAT) activities. In conclusion, the results suggest that DHA is able to modulate the inflammatory response in the immune celsl at a dose of 75 µM/mL and to boost disease resistance in common carp fed on a diet supplemented with DHA at 20 g/kg of feed.

[Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury].

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 µg·mL~(-1)) group, and TFR(30 µg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.