Adaptive Nutrition Intervention Stabilizes Serum Phosphorus Levels in Hemodialysis Patients: A Multicenter Decentralized Clinical Trial Using Real-World Data.

OBJECTIVE: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records. METHODS: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed. RESULTS: Meal intervention statistically significantly stabilized serum phosphorus level (ß = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy. CONCLUSION: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention.

Effects of perioperative vitamin E and zinc co-supplementation on systemic inflammation and length of stay following coronary artery bypass graft surgery: a randomized controlled trial.

OBJECTIVES: Coronary artery bypass graft (CABG) surgery has been reported to be associated with lower postoperative plasma antioxidant and zinc levels. We hypothesized that perioperative supplementation of vitamin E and zinc might improve short-term postoperative outcomes. METHODS: In this placebo-controlled double-blind, randomized study, patients undergoing CABG performed with cardiopulmonary bypass were recruited. The intervention group received zinc and vitamin E supplementation (1200 IU vitamin E and 120 mg elemental zinc) the day before surgery, followed by postoperative daily supplementation of 30 mg zinc and 200 IU vitamin E from the 2nd day after surgery to 3 weeks. The control group received placebos. Length of stay (LOS) in the intensive care unit and hospital, sequential organ failure assessment score on 3rd day after surgery, and plasma inflammatory markers on days 3 and 21 post-surgery were evaluated. RESULTS: Seventy-eight patients completed the study (40 in the intervention group and 38 in the placebo group). The hospital LOS was significantly shorter (p < 0.05) in the intervention group. Postoperative changes in plasma albumin levels were not different between the two groups. The plasma zinc level was higher (p < 0.0001), but plasma C-reactive protein (p = 0.01), pentraxin 3 (p < 0.0001), interferon γ (p < 0.05), malondialdehyde (p < 0.05), and aspartate aminotransferase (p < 0.01) were lower in the intervention group compared to the placebo group. CONCLUSIONS: Perioperative vitamin E and zinc supplementation significantly reduced hospital LOS and the inflammatory response in CABG surgery patients. In these patients, the optimal combination and dose of micronutrients need further study but could include zinc and vitamin E. CLINICAL TRIAL REGISTRY: This trial was registered at ClinicalTrials.gov website (NCT05402826).

Effects of swimming exercise combined with silymarin and vitamin C supplementation on hepatic inflammation, oxidative stress, and histopathology in elderly rats with high-fat diet-induced liver damage.

OBJECTIVES: The aim of this study was to demonstrate that swimming exercise combined with silymarin and vitamin C supplementation improves hepatic inflammation, oxidative stress, and liver histopathology in elderly rats with high-fat diet-induced liver damage. METHODS: Forty elderly male Wistar rats were randomly assigned to five groups (n = 8 in each): a normal diet (control), a high-fat diet (HFD), HFD + silymarin and vitamin C supplementation (HFD+Sup), HFD + swimming exercise (HFD+Exe), and HFD+Sup+Exe group (HFD+Sup+Exe). The non-alcoholic fatty liver model was induced for 6 wk in the HFD groups. After 6 wk of consuming an HFD, a daily supplemental gavage was administered to rats as an intervention along with HFD in the supplement groups for 8 wk. Moreover, rats in the exercise groups were subjected to swimming exercise training 5 d/wk for the same period. RESULTS: The combination of swimming training and supplementation caused significant decreases in liver inflammatory biomarkers tumor necrosis factor-α and interleukin-1ß while increasing total antioxidant capacity and peroxisome proliferator-activated receptor α (P < 0.05). CONCLUSION: In elderly rats with liver injury caused by an HFD, the combination of exercise and silymarin with vitamin C supplementation effectively reduced oxidative stress, liver inflammation, fat accumulation, and regulated liver enzymes.

Does the Combination of Finnish Sauna Bathing and Other Lifestyle Factors Confer Additional Health Benefits? A Review of the Evidence.

Sauna bathing, a tradition deeply rooted in the Finnish culture, has been used for thousands of years for leisure, relaxation, and wellness. Sauna bathing is linked with substantial health benefits beyond its use for leisure and relaxation. Several observational and interventional studies suggest that regular or frequent sauna bathing reduces the incidence of vascular and nonvascular diseases, such as hypertension, cardiovascular disease, dementia, and respiratory conditions; may improve the severity of conditions such as musculoskeletal disorders, COVID-19, headache, and influenza; and increases the life span. The beneficial effects of sauna bathing on adverse outcomes have been linked to its blood pressure-reducing, anti-inflammatory, antioxidant, cytoprotective, and stress-reducing properties and its synergistic effect on neuroendocrine, circulatory, cardiovascular, and immune function. Evidence suggests that frequent sauna bathing is an emerging protective risk factor that may augment the beneficial effects of other protective risk or lifestyle factors, such as physical activity and cardiorespiratory fitness, or attenuate or offset the adverse effects of other risk factors, such as high blood pressure, systemic inflammation, and low socioeconomic status. This review summarizes the available epidemiologic and interventional evidence linking the combined effects of Finnish sauna bathing and other risk factors on vascular outcomes including cardiovascular disease and intermediate cardiovascular phenotypes, nonvascular outcomes, and mortality. We also discuss the mechanistic pathways underlying the joint contributions of Finnish sauna bathing and other risk factors on health outcomes, the public health and clinical implications of the findings, gaps in the existing evidence base, and future directions.

Resolution of Cerebral Inflammation Following Subarachnoid Hemorrhage.

BACKGROUND: Aneurismal subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke that, despite improvement through therapeutic interventions, remains a devastating cerebrovascular disorder that has a high mortality rate and causes long-term disability. Cerebral inflammation after SAH is promoted through microglial accumulation and phagocytosis. Furthermore, proinflammatory cytokine release and neuronal cell death play key roles in the development of brain injury. The termination of these inflammation processes and restoration of tissue homeostasis are of utmost importance regarding the possible chronicity of cerebral inflammation and the improvement of the clinical outcome for affected patients post SAH. Thus, we evaluated the inflammatory resolution phase post SAH and considered indications for potential tertiary brain damage in cases of incomplete resolution. METHODS: Subarachnoid hemorrhage was induced through endovascular filament perforation in mice. Animals were killed 1, 7 and 14 days and 1, 2 and 3 months after SAH. Brain cryosections were immunolabeled for ionized calcium-binding adaptor molecule-1 to detect microglia/macrophages. Neuronal nuclei and terminal deoxyuridine triphosphate-nick end labeling staining was used to visualize secondary cell death of neurons. The gene expression of various proinflammatory mediators in brain samples was analyzed by quantitative polymerase chain reaction. RESULTS: We observed restored tissue homeostasis due to decreased microglial/macrophage accumulation and neuronal cell death 1 month after insult. However, the messenger RNA expression levels of  interleukin 6  and  tumor necrosis factor α were still elevated at 1 and 2 months post SAH, respectively. The gene expression of interleukin 1ß reached its maximum on day 1, whereas at later time points, no significant differences between the groups were detected. CONCLUSIONS: By the herein presented molecular and histological data we provide an important indication for an incomplete resolution of inflammation within the brain parenchyma after SAH. Inflammatory resolution and the return to tissue homeostasis represent an important contribution to the disease's pathology influencing the impact on brain damage and outcome after SAH. Therefore, we consider a novel complementary or even superior therapeutic approach that should be carefully rethought in the management of cerebral inflammation after SAH. An acceleration of the resolution phase at the cellular and molecular levels could be a potential aim in this context.

Moxibustion Treatment of COVID-19 and Rehabilitation Period of COVID-19: A Scoping Review.

Objective: The aim of this study is to provide a scoping review of the clinical literature on moxibustion therapy for the treatment of Coronavirus disease 2019 (COVID-19). Design: The PubMed, Embase, Cochrane Library, MEDLINE, CNKI, Wanfang, and VIP databases were searched from January 1, 2020, to August 31, 2022. Essential data were extracted from each article, and the data were displayed using tables and graphs. The study did not require IRB approval. Results: This scoping review included 14 research articles: 8 observational studies, 5 randomized controlled trials, and 1 nonrandomized clinical trial. All the studies were published by Chinese scholars. The findings revealed that moxibustion can contribute to reducing the symptoms of patients with COVID-19, improving inflammation and immune indicators, and shortening the time of nucleic acid negative conversion. Moxibustion confers curative effects on patients of all ages and degrees of illness. In addition, moxibustion can optimize the prognosis of patients in the rehabilitation period. The most commonly chosen acupoints are ST36, RN4, RN8, and RN12. No side effect was mentioned in the included studies. Conclusion: Moxibustion can produce a good effect in the treatment and rehabilitation of patients with COVID-19. It is safe, effective, simple, and noninvasive and should be included as standard care.

Inflammation-related proteomics demonstrate landscape of fracture blister fluid in patients with acute compartment syndrome.

Background: Blisters are tense vesicles or bullae that arise on swollen skin and are found in a wide range of injuries. As a complication of fracture, fracture blisters are considered soft tissue injuries, which often lead to adverse effects such as prolonged preoperative waiting time and increased risk of surgical site infection. However, our previous study found that in patients with acute compartment syndrome, fracture blisters may be a form of compartment pressure release, but the specific mechanism has not been revealed. Here, we mapped out the proteomic landscape of fracture blister fluid for the first time and compared its expression profile to cupping and burn blisters. Methods: First, fluid samples were collected from 15 patients with fracture blisters, 7 patients with cupping blisters, and 9 patients with burn blisters. Then, the expression levels of 92 inflammatory proteins were measured using the Olink Target 96 Inflammation panel. Protein profiles were compared across the three groups using Differential Protein Expression Analysis and Principal Component Analysis (PCA). Results: Fracture blisters had significantly higher levels of 50 proteins in comparison to cupping and 26 proteins in comparison to burn blisters. Notably, PCA showed fracture blisters closely resembled the protein expression profile of burn blisters but were distinct from the protein expression profile of cupping blisters. Conclusion: Our study provides the first characterization of fracture blister fluid using proteomics, which provides a valuable reference for further analysis of the difference between blisters caused by fractures and those caused by other pathogenic factors. This compendium of proteomic data provides valuable insights and a rich resource to better understand fracture blisters.

Dietary Inflammatory Index and Fractures in Midlife Women: Study of Women's Health Across the Nation.

CONTEXT: While evidence suggests that chronic, low-grade inflammation is a risk factor for bone loss and fractures, the potential relation between an inflammatory dietary profile and greater fracture risk is uncertain. OBJECTIVE: We examined whether a more inflammatory diet, consumed during pre- and early perimenopause, is associated with more incident fractures starting in the menopause transition (MT) and continuing into postmenopause. METHODS: Dietary inflammatory potential was quantified using 2 energy-adjusted dietary inflammatory index scores: one for diet only (E-DII), and one for diet plus supplements (E-DII-S). We included 1559 women from the Study of Women's Health Across the Nation, with E-DII and E-DII-S scores from the baseline visit (during pre- or early perimenopausal), and up to 20 years of follow-up. We excluded women using bone-beneficial medications at baseline; subsequent initiators were censored at first use. The associations of E-DII or E-DII-S (each tested as separate exposures) with incident fracture were examined using Cox proportional hazards regression. RESULTS: Adjusted for age, BMI, cigarette use, diabetes, MT stage, race/ethnicity, prior fracture, bone-detrimental medication use, aspirin or nonsteroidal anti-inflammatory drug use, and study site, greater E-DII and E-DII-S (tested separately) were associated with more future fractures. Each SD increment in E-DII and E-DII-S predicted 28% (P = .005) and 21% (P = .02) greater fracture hazard, respectively. Associations were essentially unchanged after controlling for bone mineral density. CONCLUSION: A more pro-inflammatory diet in pre- and early perimenopause is a risk factor for incident fracture. Future studies should consider whether reducing dietary inflammation in midlife diminishes fracture risk.

Salvianolic acid A alleviates atherosclerosis by inhibiting inflammation through Trc8-mediated 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation.

BACKGROUND: Atherosclerosis is the most prevalent cardiovascular disease and remains the major contributor to death and mortality globally. Salvianolic acid A (SalA) is a water-soluble phenolic acid that benefits atherosclerosis. However, the mechanisms of SalA protecting against atherosclerosis remain unclear. PURPOSE: We aimed to determine whether SalA prevents atherosclerosis by modulating 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) degradation via the ubiquitin-proteasomal pathway. METHODS: The animal and cellular models of atherosclerosis were established by subjecting apolipoprotein E (ApoE) knockout mice to a high-fat diet (HFD) and exposing human umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein (ox-LDL), respectively. RESULTS: Our results showed that similar to atorvastatin, SalA suppressed atherosclerotic plaque formation, improved serum lipid accumulation, and reduced cholesterol levels in HFD-fed ApoE-/- mice. Moreover, SalA protected HUVECs from ox-LDL-caused cell viability reduction and lipid accumulation. The mechanism study revealed that SalA reduced the production of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6, and augmented the generation of the anti-inflammatory cytokine IL-10 in ApoE-/- mice and HUVECs, accompanied by increased HMGCR ubiquitination and degradation via translocation in renal carcinoma on chromosome 8 (Trc8), insulin-induced gene (Insig)1 and Insig2. Furthermore, the knockdown of Trc8 abolished the SalA-induced HMGCR degradation and anti-atherosclerosis activity. CONCLUSION: SalA rescues atherosclerosis by inhibiting inflammation through the Trc8-regulated degradation of HMGCR. These findings underscore Trc8 as a potential target of atherosclerosis.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

Effect of the phosphate binder sucroferric oxyhydroxide in dialysis patients on endogenous calciprotein particles, inflammation, and vascular cells.

BACKGROUND: Calciprotein particles (CPPs), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in dialysis patients, with putative links to vascular calcification, endothelial dysfunction and inflammation. We hypothesized that phosphate binder therapy with sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels and attenuate pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro. METHODS: This secondary analysis of a randomised controlled crossover study compared the effect of 2-week phosphate binder washout with high-dose (2000 mg/day) and low-dose (250 mg/day) SO therapy in 28 haemodialysis patients on serum CPP levels, inflammatory cytokine/chemokine arrays and human aortic smooth muscle cell (HASMC) and coronary artery endothelial cell (HCAEC) bioassays. RESULTS: In our cohort (75% male, 62 ± 12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP levels {-62% [95% confidence interval (CI) -76 to -44], P < .0001 and -38% [-62 to -0.14], P < .001, respectively} compared with washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in interleukin-6 (IL-6) and IL-8. Exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8 and vascular cell adhesion protein 1) compared with washout. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of the CPP-containing fraction from patient sera. Effects of CPP removal were confirmed in an independent cohort of chronic kidney disease patients. CONCLUSIONS: High-dose SO reduced endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.

Inflammation, sauna bathing, and all-cause mortality in middle-aged and older Finnish men: a cohort study.

Inflammation and sauna bathing are each related to the risk of all-cause mortality. The interplay between inflammation, sauna bathing and all-cause mortality is not well understood. We aimed to evaluate the separate and joint associations of inflammation (high sensitivity C-reactive protein, hsCRP) and frequency of sauna bathing (FSB) with all-cause mortality in a cohort of Caucasian men. We used the Kuopio Ischaemic Heart Disease Study cohort comprising 2575 men aged 42-61 years at baseline. Serum hsCRP was measured using an immunometric assay and sauna bathing habits were assessed by a self-administered questionnaire. High sensitivity CRP was categorized as normal and high (≤ 3 and > 3 mg/L, respectively) and FSB as low and high (defined as ≤ 2 and 3-7 sessions/week respectively). A total of 1618 deaths occurred during a median follow-up of 27.8 years. Comparing high vs normal hsCRP levels, the multivariable-adjusted HR (95% CI) for all-cause mortality was 1.27 (1.13-1.44). Comparing high vs low FSB, the multivariable-adjusted HR (95% CI) for all-cause mortality was 0.86 (0.76-0.97). Compared with normal hsCRP-low FSB, high hsCRP-low FSB was associated with an increased risk of all-cause mortality 1.28 (1.12-1.47), with no evidence of an association for high hsCRP-high FSB and all-cause mortality risk 1.06 (0.81-1.40). Positive additive and multiplicative interactions were found between hsCRP and FSB in relation to mortality. In a general Finnish male population, both hsCRP and FSB are each independently associated with all-cause mortality. However, frequent sauna baths appear to offset the increased all-cause mortality risk related to high hsCRP levels.

Ameliorating effects of electroacupuncture on the low-grade intestinal inflammation in rat model of diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIM: We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: IBS-D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS-D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS-D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t-test or Mann-Whitney U-test. Differences among more than two groups were compared using one-way ANOVA or Kruskal-Wallis test. RESULTS: After modeling, the results of HE staining in intestinal tract of IBS-D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS-D rats were correlated with the changes of intestinal mucosa. CONCLUSION: EA may treat intestinal LGI in IBS-D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.

Attenuation of low-grade chronic inflammation by phytonutrients: A computational systems biology analysis.

BACKGROUND: Low-grade chronic inflammation (LGCI) is a strong and independent risk factor for many chronic diseases, like cardiovascular, musculoskeletal, metabolic, and neurological conditions. Dietary intervention studies have reported evidence for the role of plant-derived flavonoids in modulation of LGCI. This research explores the efficacy of Fruit/Berry/Vegetable (FBV) juice powder on LGCI. METHODS: The study employs computational systems biology: 1) to identify biomolecular mechanisms of LGCI; 2) to identify the bioactive compounds of FBV juice powder and their specific effects on mechanisms of LGCI; and, 3) to predict the quantitative effects of those bioactive compounds on LGCI. RESULTS: Four molecular pathways that are affected by the compounds of FBV include: 1) TNF-α production; 2) CCL2 production; 3) IL-1ß production; and 4) reactive oxygen species production. The bioactive compounds including luteolin, epicatechin, epigallocatechin gallate, lycopene, quercetin, vitamin A, vitamin C and vitamin E in FBV significantly lowered TNF-α production, CCL2 production, IL-1ß production, and reactive oxygen species production. CONCLUSION: FBV provides a combination of active ingredients that synergistically affect multiple modalities of low grade chronic inflammation to help improve blood circulation and energy levels, and lower muscle soreness.

Effect of different dietary fats on inflammation and glucose intolerance in high fructose and high fat fed experimental animals.

OBJECTIVES: Diet is the major modifiable risk factor for the onset of insulin resistance and its progression into diabetes. In the present study the effect of various dietary fats on inflammatory homeostasis and glucose tolerance is investigated in high fat and high fructose fed mice model. METHODS: C57/BL6J mice were divided into four groups and fed a casein-based diet containing high fructose (45%) and high fat (24%) (clarified butter oil [CBO]; safflower oil [SFFO] and lard oil [LO]) for 120 days; oral glucose tolerance (OGTT), plasma lipid profile and plasma & adipose tissue cytokines levels were compared with the control diet (10% groundnut oil and 59.5% starch) fed animals. RESULTS: The total cholesterol and triglycerides were higher in CBO and LO fed animals with glucose intolerance and increased body weights; liver and white adipose tissue weights were higher in CBO and LO fed animals respectively. CBO feeding increased the plasma (IFN-γ) and adipose tissue cytokines (IFN-γ, IL-10, IL-6 & TNF-α). LO feeding increased plasma IFN-γ, TNF-α and IL-1ß and adipose tissue IL-6. SFFO feeding decreased body weight and tissue cytokines and increased plasma IFN-γ levels without causing impairment in the glucose tolerance. CONCLUSIONS: Consumption of a high fructose and high fat diet which mimic the present-day dietary pattern resulted in altered inflammatory homeostasis and impairment in glucose tolerance in 24% CBO and LO fed animals. The deleterious effects of high fructose feeding were reversed in SFFO fed mice possibly due to the presence of oleic and linoleic acids.

Qing Zao Fang (QZF) Alleviates the Inflammatory Microenvironment of the Submandibular Gland in Sjögren's Syndrome Based on the PI3K/Akt/HIF-1α/VEGF Signaling Pathway.

Sjögren's syndrome (SS) which could lead to a disorder of our immune system is a chronic autoimmune disease characterized by invading exocrine glands such as salivary glands and lacrimal glands and other exocrine glands. Its common symptom is dry mouth and dry eyes, often accompanied by a large number of lymphocyte infiltrations and can involve other organs to cause complex clinical manifestations. In this study, we aimed at investigating the effect of QZF in SS, identifying the molecular mechanism in modulating autoimmune response, and determining the important roles of these factors' function as a modulator in the pathogenesis of SS. The NOD mice were utilized to establish the rats' model of Sjögren's syndrome. After 10 weeks' hydroxychloroquine and QZF in different dose interference, submandibular gland tissue was collected. The therapeutic effect of QZF on SS rats was identified, and the results suggest the comparable potential to hydroxychloroquine. In submandibular gland tissue, interleukin- (IL-) 17 was significantly lower in high-dose QZF than that in SS rats and the focal lymphocytes were highly attenuated. Moreover, we found that PI3K/Akt signals were activated and the downstream HIF-1α/VEGF signals were enhanced in SS rats whose protein expression could be inhibited by QZF treatment. In addition, QZF could modulate autophagy in submandibular gland tissue and then inhibit the inflammation response and therefore facilitate the tissue repair.

Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases.

Phenotyping cardiovascular illness and recognising heterogeneities within are pivotal in the contemporary era. Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1ß and -6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship. As for future perspectives, artificial intelligence in conjunction with machine learning could better elucidate the sequencing of the microbiome and data mining. Comprehensively understanding the interplay between the gut microbiome and its cardiovascular impact will help identify future therapeutic targets, affording holistic care for patients with cardiovascular diseases.

Alumina nanoparticles-induced heterophil extracellular traps exacerbate liver injury by regulating oxidative stress and inflammation in chickens.

Widely used alumina nanoparticles (Al2O3 NPs) exposed to the environment pose a serious threat to human and animal health. The formation of heterophil extracellular traps (HETs) is a mechanism of innate immune defense against infection, but excessive HETs cause pathological damage. Here, we aim to explore the influence and mechanism of Al2O3 NPs on the formation of HETs in vitro, and further investigate the role of HETs release in histopathological damage after Al2O3 NPs treatment. Immunofluorescence analysis showed that Al2O3 NPs induced the formation of HETs, which was characterized by modified histones and elastase in the DNA backbone. Fluorescence microplate analysis showed that HETs formation was dependent on NADPH oxidase, P38, extracellular regulated protein kinases (ERK1/2) pathways and glycolysis. In vivo investigation showed that Al2O3 NPs significantly caused HETs release and liver damage. Biochemical analysis showed that Al2O3 NPs inhibited the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). Real-time fluorescence quantification results showed that Al2O3 NPs caused the overexpression of inflammation-related molecules interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), caspase-1 and caspase-11. All these changes were significantly changed by DNase I (Degradation reagent for HETs). Together, these suggest that Al2O3 NPs-induced HETs exacerbate liver injury by regulating oxidative stress and inflammatory responses, which provide a new perspective and potential prophylaxis and treatment targets for Al2O3 NPs toxicological research.

Preliminary experience on the use of sucrosomial iron in hemodialysis: focus on safety, hemoglobin maintenance and oxidative stress.

PURPOSE: Iron is usually administered in hemodialysis patients by parenteral route, as oral absorption is poor due to high hepcidin levels. However, administrations of intravenous iron and iron overload are associated with high oxidative stress and systemic inflammation that can affect patient survival. With this study, we evaluated an alternative type of oral iron for the treatment of anemia in hemodialysis patients. The formulation consists in ferric pyrophosphate covered by phospholipids plus sucrose ester of fatty acid matrix, named sucrosomial iron, whose absorption is not influenced by hepcidin. METHODS: Twenty-four (24) patients undergoing chronic hemodialysis switched iron supplementation from intravenous (ferric gluconate 62.5 mg weekly) to oral (sucrosomial iron, 90 mg weekly in 3 administrations of 30 mg) route for 3 months. Classical anemia, iron metabolism, inflammation and nutritional biomarkers were monitored, as well as biomarkers of oxidative stress, such as protein-bound di-tyrosines, protein carbonylation, advanced oxidation protein products and protein thiols. RESULTS: Over the 3 months, hemoglobin values remained stable, as the values of hematocrit and mean corpuscular volume. In parallel, other anemia parameters dropped, including ferritin, transferrin saturation and serum iron. On the other side, nutritional biomarkers, such as total proteins and transferrin, increased significantly during the time frame. We also observed a significant decrease in white blood cells as well as a non-significant reduction in C-reactive protein and some oxidative stress biomarkers, such as protein carbonyls and di-tyrosines. CONCLUSION: Our study demonstrates that a therapy with sucrosomial iron in hemodialysis patients is safe and can maintain stable hemoglobin levels in a three-month period with a possible beneficial effect on oxidative stress parameters. However, the reduction of ferritin and transferrin saturation suggests that a weekly dosage of 90 mg is not sufficient in hemodialysis patients in the long time to maintain hemoglobin.

Preliminary study on alleviation of heat-induced intestinal inflammation through compensatory effects of glucose oxidase.

1. The influence of glucose oxidase (GOD) supplementation on growth, gut inflammation and its compensatory effects in broilers was investigated before and after heat stress.2. Before heat stress, one-day-old broilers were divided into two groups: the control (CON) and GOD (100 g/t complete feed) groups. On d 21, the CON group was equally divided into CON1 and CON2 groups, and heat stress (35°C) was applied to the CON2 and GOD groups for 8 h/day to the end of the study, d 27 of age. The chickens were either killed before heat stress and 2 d after heat stress for the determination of cytokines in the liver and ileum, serum antioxidant enzymes and ileal microbiota. Growth performance was determined before and 7 d after heat stress.3. The GOD decreased Clostridiales and Enterobacteriaceae families of bacteria and increased ileal nuclear factor-κB, interleukin-1ß, and interferon-γ (P < 0.05) before heat stress. The broilers exhibited compensatory effects, including increases in ileal sirtuin-1, heat shock protein 70 expression, liver nuclear factor erythroid 2-related factor 2 content, serum total antioxidant capacity and glutathione peroxidase level (P < 0.05). At 2 d after heat stress, inflammatory factors were increased in both the CON2 and GOD groups, but the levels were lower in the GOD than CON2 (P < 0.05). On d 7 after heat stress, GOS alleviated heat stress induced growth retardation (P < 0.05).4. These data suggested that GOD supplementation in broiler diets before heat stress stimulated intestinal oxidative stress and produced a compensatory response, which prevented a rapid increase in intestinal inflammatory factors and helped to maintain growth performance under heat stress.