Anti-inflammatory Functions Research Articles

Molecularly imprinted composite membranes with the dual imprinted network for highly selective separation of acteoside

Acteoside (ACT) is the main active ingredient in phenylethanoid glycosides (PhGs) and it has anti-inflammatory, liver-protecting, and memory-enhancing functions. It remained a challenge to develop an imprinted membrane with high permselectivity for separation of ACT from PhGs. In this paper, ACT was used as a template molecule to design dual imprinted molecularly imprinted composite membranes (DIMICMs). The dual imprinted network structure was constructed and played a vital role in DIMICMs. On one hand, ACT imprinted network was formed on the surface of ACT-KH570/PDA/CMK-3@PVDF, and it can recognize and adsorb ACT. On the other hand, the imprinted filler ACT-KH570/PDA/CMK-3 was mixed with PVDF powder to construct the ACT imprinted network in the membrane, and the imprinted network can further recognize and accommodate the ACT. The dual imprinted network acted synergistically for dual recognition of ACT. The result showed that the DIMICMs had the high permselectivity (β = 14.61), selectivity (α = 4.64) and rebinding capacity (105.58 mg/g). The designed approach of DIMICMs with a dual imprintednetwork provided a strategy for the separation of natural products.

Favourable HDL composition in endurance athletes is not associated with changes in HDL in vitro antioxidant and endothelial anti-inflammatory function.

Given the failure of high-density lipoprotein (HDL) raising therapies to reduce cardiovascular disease risk, attention has turned towards HDL composition and vascular protective functions. In individuals with insulin resistance, exercise interventions recover HDL function. However, the effect of exercise on HDL in otherwise healthy individuals is unknown. This cross-sectional study aimed to measure HDL composition and antioxidant/endothelial anti-inflammatory function in insulin sensitive endurance athlete and healthy control men. HDL was isolated using density gradient ultracentrifugation. HDL composition was measured using microplate assays for apolipoprotein A-I, total cholesterol content and apolipoprotein M. HDL protein composition was measured using nano-liquid chromatography tandem mass spectrometry. HDL subclass distribution was measured by native gel electrophoresis. HDL in vitro antioxidant function was measured by paraoxonase-1 activity assay and anti-inflammatory function assessed in endothelial cells. Compared with controls, endurance athlete HDL had higher apolipoprotein A-1 (1.65 ± 0.62 mg/ml vs 1.21 ± 0.34 mg/ml, P=0.028) and higher total cholesterol content (2.09 ± 0.44 mmol/L vs 1.54 ± 0.33 mmol/L, P<0.001). Proteomics revealed higher apolipoprotein A-II, A-IV and D and transthyretin in endurance athlete HDL versus controls. There was no difference observed in in vitro HDL antioxidant or anti-inflammatory functions between controls and endurance athletes. Despite a more favourable composition, endurance athlete HDL did not have higher in vitro antioxidant or anti-inflammatory function. It is possible that HDL has a ceiling of function, i.e. that healthy HDL function cannot be enhanced by endurance exercise.

Cloperastine Reduces IL-6 Expression via Akt/GSK3/Nrf2 Signaling in Monocytes/Macrophages and Ameliorates Symptoms in a Mouse Sepsis Model Induced by Lipopolysaccharide.

Cloperastine (CLP) is a drug with a central antitussive effect that is used to treat bronchitis. Therefore, we have attempted to examine the anti-inflammatory effects of CLP. CLP reduced the secretion of interleukin (IL)-6, a pro-inflammatory cytokine, from RAW264.7 monocyte/macrophage-linage cells treated with lipopolysaccharide (LPS). IL-6 is a biomarker of sepsis and has been suggested to exacerbate its symptoms. We found that the intraperitoneal administration of CLP reduced IL-6 levels in the lungs and also improved hypothermia in mice with LPS-induced sepsis. CLP ameliorated kidney pathologies such as congestion and increased the survival rate of mice administered with a lethal dose of LPS. To reveal the mechanisms underlying the anti-inflammatory function of CLP, we analysed the intracellular signaling in LPS-treated RAW264.7 cells. CLP induced the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3 (GSK3) and also increased the amount of nuclear factor erythroid-2-related factor 2 (Nrf2) in RAW264.7 cells with/without LPS. Wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), reduced the upregulated phosphorylation levels of Akt and GSK3 and the increased amount of Nrf2. It also halted the reduction of IL-6 secretion caused by CLP. These results suggest that CLP has an anti-inflammatory function via Akt/GSK3/Nrf2 signaling and could be a candidate drug for the treatment of inflammatory diseases, including sepsis.

Oral administration of anti-lipopolysaccharide factor isoform 3 via the bait microalga for controlling bacterial infection of Atlantic Bay scallop (Argopecten irradians)

In order to reduce antibiotic application in aquaculture, an antimicrobial peptide anti-lipopolysaccharide factor isoform 3 (ALFPm3) with highly effective inhibitory activity against pathogens was introduced to bay scallop (Argopecten irradians) using bait microalga Tetraselmis subcordiformis as a delivery system. To improve its expression and stability, a fusion of two alfpm3 genes (alfpm3–2) was inserted into an expression vector and transformed into T. subcordiformis chloroplast, followed by in vitro and in vivo functional evaluations of the antimicrobial activities of ALFPm3–2 by minimum inhibitory concentration method and bay scallop breeding experiment, respectively. The results showed that the transformants of T. subcordiformis and the purified ALFPm3–2 had significant inhibitory effects on Vibrio parahaemolyticus and Staphylococcus aureus in vitro, while feeding the transformants reduced the colonization of the two pathogens in bay scallops, which further reduced bay scallops’ mortality by 28.67 % as revealed in infection test. Furthermore, daily oral administration of ALFPm3–2 could improve the gut microbial community and reduce the inflammatory response. Combined with changes in immune factors and endotoxin, it indicated that exogenous ALFPm3–2 played antimicrobial and anti-inflammatory functions in the guts of bay scallops. Overall, this study provided strong evidence to support the oral administration of antimicrobial peptides via microalgae in aquaculture.

Growth hormone-releasing hormone and cancer.

The hypothalamic hormone growth hormone-releasing hormone (GHRH), in addition to promoting the synthesis and release of growth hormone (GH), stimulates the proliferation of human normal and malignant cells by binding to GHRH-receptor (GHRH-R) and its main splice variant, SV1. Both GHRH and GHRH-Rs are expressed in various cancers, forming a stimulatory pathway for cancer cell growth; additionally, SV1 possesses ligand independent proliferative effects. Therefore, targeting GHRH-Rs pharmacologically has been proposed for the treatment of cancer. Various classes of synthetic GHRH antagonists have been developed, endowed with strong anticancer activity in vitro and in vivo, in addition to displaying anti-inflammatory, antioxidant and immune-modulatory functions. GHRH antagonists exert indirect effects by blocking the pituitary GH/hepatic insulin-like growth factor I (IGF-I) axis, or directly inhibiting the binding of GHRH on tumor GHRH-Rs. Additionally, GHRH antagonists block the mitogenic functions of SV1 in tumor cells. This review illustrates the main findings on the antitumor effects of GHRH antagonists in experimental human cancers, along with their underlying mechanisms. The development of GHRH antagonists, with reduced toxicity and high stability, could lead to novel therapeutic agents for the treatment of cancer and inflammatory diseases.

AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp-/- mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.

Silk fibroin/chitosan-based anal fistula scaffolds loaded with curcumin and 5-aminosalicylic acid

The present work describes the development of silk fibroin (SF)/chitosan (CS)-based porous composite anal fistula scaffold (SCAFS) with anti-inflammatory and healing functions. The SCAFS comprises an inner layer made from degummed silk fiber using a vertical braiding machine, and an outer layer created by freeze-drying a mixture of short SF fibers and curcumin (CUR)/5-aminosalicylic acid (5-ASA) loaded SF/CS solution. Results revealed that the SCAFS has high porosity of 42.4 %, remarkable water absorption rate of 370.5 %, robust dry/wet compression resistance of 12.28 ± 2.61 N/3.08 ± 0.43 N. The in vitro &in vivo biocompatibility and anti-inflammatory effect of SCAFS were further examined. The expression of pro-inflammatory cytokine TNF-α, anti-inflammatory cytokine IL-10, CD31 and CD68 was determined by immunohistochemistry (IHC) staining, H&E staining, Immunofluorescence (IF) staining and Masson assay. The results showed that the scaffolds possess a sustainable drug release above 400 h, better biocompatibility and anti-inflammatory effect than the control groups (p < 0.05). Thus, the SCAFS has potential application in the treatment of Crohn's disease.

Sesquiterpenes from the fruits of Piper longum L. and their anti-inflammatory activity

The fruits of Piper longum are called long pepper, which are well-known culinary spice as well as traditional medicine. In present work, thirteen sesquiterpenes including four undescribed compounds were isolated from P. longum fruits. Compound 1 was a rare methylated bisabolane-type sesquiterpene. Compounds (−)-3 and (+)-3 were a pair of enantiomers of an uncommon humulane which were separated by chiral HPLC. The absolute configurations of compounds 1–3 were confirmed through the means of spectroscopic data analyses, 13C NMR calculations employing DP4+ probability analyses, and ECD calculations. Compounds 2 and 11 presented moderated inhibitory effect on the NO release in LPS-induced RAW264.7 cells with IC50 values of 30.65 ± 0.90 and 38.48 ± 2.42 μM, respectively. Above results enriched the chemical information of P. longum fruits, and meanwhile provided scientific evidences for the anti-inflammatory function of P. longum fruits.

Potential Player of Platelet in the Pathogenesis of Cardiotoxicity: Molecular Insight and Future Perspective.

Cancer patients may encounter the onset of cardiovascular disease due to tumor advancement or chemotherapy, commonly known as "cardiotoxicity." In this respect, the conventional chemotherapy treatment protocol involves a mixture of different medications. These medications can be detrimental to cardiac tissue, consequently exposing the patient to the possibility of irreversible cardiac injury. The enhancement of oxidative stress and inflammation is an important mechanism of chemotherapeutic agents for developing cardiotoxicity. Regarding their dual pro- and anti-inflammatory functions, platelets can significantly influence the progression or suppression of cardiotoxicity. Therefore, the expression of platelet activatory markers can serve as valuable prognostic indicators for cardiotoxicity. The primary objective of this study is to examine the significance of platelets in cardiotoxicity and explore potential strategies that could effectively target malignant cells while minimizing their cytotoxic impact, such as cardiotoxicity and thrombosis.

Ginsenosides as Promising Therapeutic Agents for Glioma: Mechanisms of Action and Future Perspectives

Abstract: Brain cancers, particularly gliomas, are a significant cause of mortality worldwide. Gliomas are primary tumors of the central nervous system (CNS) and are characterized by diverse clinical and biological features. Despite advancements in clinical approaches and surgical techniques, the treatment of high-grade gliomas still poses multiple challenges. This article focuses on a key active substance found in Panax ginseng called Ginsenosides. Ginsenosides belong to a specific class of triterpenoid saponins and have demonstrated various therapeutic effects, including neuroprotective, anticancer, anti-inflammatory, and neuroprotective functions. These compounds have shown potential in the treatment of gliomas and other cancers. Several pathways associated with ginsenosides, such as Rg3, Rh2, Rd, and Rb1, have been extensively studied, and these compounds have been proposed as potential targets in glioma treatment. The precise mechanisms of action of ginsenosides in gliomas are still being investigated, but their ability to modulate various signalling pathways and exert multiple therapeutic effects makes them promising candidates for further research and development. Clinical trials and additional studies are necessary to validate their therapeutic benefits and determine the optimal dosage, administration route, and potential combination with other treatment modalities. In summary, ginsenosides, the active compounds found in Panax ginseng, exhibit various therapeutic effects, including potential anti-cancer properties in gliomas. Their ability to modulate multiple pathways makes them promising targets for further research in the field of glioma treatment. However, more studies are required to establish their effectiveness and safety in clinical settings.

Hyperbaric oxygen therapy in the ATLS/ACLS resuscitative management of acutely ill or severely injured patients with severe anemia: a review.

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen can resupply adenosine triphosphate for energy for gene expression and reparative and anti-inflammatory cellular function. This advantageous effect is termed the hyperbaric oxygen paradox. Similarly, the normobaric oxygen paradox has been used to elicit erythropoietin expression. Referfusion injury after an ischemic insult can be ameliorated by hyperbaric oxygen administration. Oxygen toxicity can be averted by short hyperbaric oxygen exposure times with air breaks during treatments and also by lengthening the time between hyperbaric oxygen sessions as the treatment advances. Hyperbaric chambers can be assembled to provide everything available to a patient in modern-day intensive care units. The complication rate of hyperbaric oxygen therapy is very low. Accordingly, hyperbaric oxygen, when safely available in hospital settings, should be considered as an adjunct for the management of critically injured or ill patients with disabling anemia.

Histone deacetylase 7 activates 6-phosphogluconate dehydrogenase via an enzyme-independent mechanism that involves the N-terminal protein-protein interaction domain.

Histone deacetylase 7 (HDAC7) is a member of the class IIa family of classical HDACs with important roles in cell development, differentiation, and activation, including in macrophages and other innate immune cells. HDAC7 and other class IIa HDACs act as transcriptional repressors in the nucleus but, in some cell types, they can also act in the cytoplasm to modify non-nuclear proteins and/or scaffold signalling complexes. In macrophages, HDAC7 is a cytoplasmic protein with both pro- and anti-inflammatory functions, with the latter activity involving activation of the pentose phosphate pathway (PPP) enzyme 6-phosphogluconate dehydrogenase (6PGD) and the generation of anti-inflammatory metabolite ribulose-5-phosphate. Here, we used ectopic expression systems and biochemical approaches to investigate the mechanism by which HDAC7 promotes 6PGD enzyme activity. We reveal that HDAC7 enzyme activity is not required for its activation of 6PGD and that the N-terminal protein-protein interaction domain of HDAC7 is sufficient to initiate this response. Mechanistically, the N-terminus of HDAC7 increases the affinity of 6PGD for NADP+, promotes the generation of a shorter form of 6PGD, and enhances the formation of higher order protein complexes, implicating its scaffolding function in engagement of the PPP. This contrasts with the pro-inflammatory function of HDAC7 in macrophages, in which it promotes deacetylation of the glycolytic enzyme pyruvate kinase M2 for inflammatory cytokine production.

12440 Exploring The Potential Protective Role Of The Bacterial-derived Metabolite Indole-3-propionic Acid Against Obesogenic Insults In Placenta Cell Lines

Abstract Disclosure: J. Ernst: None. L. Conlon: None. R. Gupta: None. L. Kang: None. M.E. Heard-Lipsmeyer: None. Obesity during pregnancy is associated with detrimental changes in placental function that lead to the development of complications such as gestational diabetes and preeclampsia as well as altered metabolism in the offspring. With the incidence of obesity reaching epidemic levels world-wide, it is imperative to find mechanisms to mitigate these risks during pregnancy. The gut-microbiome is a diverse system that regulates numerous body functions through the secretion of specific metabolites. Gut dysbiosis has recently emerged as one mechanism that contributes to placental dysfunction and clear associations between obesity and gut dysbiosis are evident. Indole-3-propionic acid (IPA) is a gut microbiome-derived metabolite that has anti-inflammatory, anti-oxidative stress and glucose regulatory functions, all of which are dysregulated in obesity. Previous studies have found diminished levels of IPA in serum of women with overweight/obesity. However, it remains unknown what the physiological functions of IPA are in the placenta and if it could have potential protective effects against perturbations caused by obesity. The objective of this study is to determine what physiological role IPA plays in the placenta and if IPA can protect against obesogenic insults that contribute to placental pathology. For this study, we developed an in vitro model of obesity where two human placental cell lines, BeWo (choriocarcinoma) and HTR8 (normal immortalized trophoblasts) were cultured in media conditioned by mature human adipocytes (ACM). RNA sequencing (RNAseq) analysis was used to determine acute effects of IPA treatment after 24 hours in the presence and absence of ACM. We further examined the influence of IPA on insulin signaling with physiological and hyperinsulinemia levels of insulin at 24 and 72 hours utilizing QPCR and western blot analyses. RNAseq analysis revealed treatment with physiological levels of IPA induced changes in genes associated with normal placental function, autophagy and inflammatory mediated processes and other pathways. Our RNAseq analysis offers initial insight into the molecular mechanisms of IPA in placental cells. Future analyses will investigate the potential role of insulin signaling, glucose homeostasis and oxidative stress. Collectively, this study highlights the importance of a healthy gut microbiome and potentially serves as a window of opportunity to mitigate the onset or severity of pregnancy-related disorders such as gestational diabetes by enhancing the gut microbiome prior to pregnancy. Presentation: 6/1/2024

12440 Exploring The Potential Protective Role Of The Bacterial-derived Metabolite Indole-3-propionic Acid Against Obesogenic Insults In Placenta Cell Lines

Abstract Disclosure: J. Ernst: None. L. Conlon: None. R. Gupta: None. L. Kang: None. M.E. Heard-Lipsmeyer: None. Obesity during pregnancy is associated with detrimental changes in placental function that lead to the development of complications such as gestational diabetes and preeclampsia as well as altered metabolism in the offspring. With the incidence of obesity reaching epidemic levels world-wide, it is imperative to find mechanisms to mitigate these risks during pregnancy. The gut-microbiome is a diverse system that regulates numerous body functions through the secretion of specific metabolites. Gut dysbiosis has recently emerged as one mechanism that contributes to placental dysfunction and clear associations between obesity and gut dysbiosis are evident. Indole-3-propionic acid (IPA) is a gut microbiome-derived metabolite that has anti-inflammatory, anti-oxidative stress and glucose regulatory functions, all of which are dysregulated in obesity. Previous studies have found diminished levels of IPA in serum of women with overweight/obesity. However, it remains unknown what the physiological functions of IPA are in the placenta and if it could have potential protective effects against perturbations caused by obesity. The objective of this study is to determine what physiological role IPA plays in the placenta and if IPA can protect against obesogenic insults that contribute to placental pathology. For this study, we developed an in vitro model of obesity where two human placental cell lines, BeWo (choriocarcinoma) and HTR8 (normal immortalized trophoblasts) were cultured in media conditioned by mature human adipocytes (ACM). RNA sequencing (RNAseq) analysis was used to determine acute effects of IPA treatment after 24 hours in the presence and absence of ACM. We further examined the influence of IPA on insulin signaling with physiological and hyperinsulinemia levels of insulin at 24 and 72 hours utilizing QPCR and western blot analyses. RNAseq analysis revealed treatment with physiological levels of IPA induced changes in genes associated with normal placental function, autophagy and inflammatory mediated processes and other pathways. Our RNAseq analysis offers initial insight into the molecular mechanisms of IPA in placental cells. Future analyses will investigate the potential role of insulin signaling, glucose homeostasis and oxidative stress. Collectively, this study highlights the importance of a healthy gut microbiome and potentially serves as a window of opportunity to mitigate the onset or severity of pregnancy-related disorders such as gestational diabetes by enhancing the gut microbiome prior to pregnancy. Presentation: 6/1/2024

C5a Induces Inflammatory Signaling and Apoptosis in PC12 Cells through C5aR-Dependent Signaling: A Potential Mechanism for Adrenal Damage in Sepsis.

The complement system is critically involved in the pathogenesis of sepsis. In particular, complement anaphylatoxin C5a is generated in excess during sepsis, leading to cellular dysfunction. Recent studies have shown that excessive C5a impairs adrenomedullary catecholamine production release and induces apoptosis in adrenomedullary cells. Currently, the mechanisms by which C5a impacts adrenal cell function are poorly understood. The PC12 cell model was used to examine the cellular effects following treatment with recombinant rat C5a. The levels of caspase activation and cell death, protein kinase signaling pathway activation, and changes in inflammatory protein expression were examined following treatment with C5a. There was an increase in apoptosis of PC12 cells following treatment with high-dose C5a. Ten inflammatory proteins, primarily involved in apoptosis, cell survival, and cell proliferation, were upregulated following treatment with high-dose C5a. Five inflammatory proteins, involved primarily in chemotaxis and anti-inflammatory functions, were downregulated. The ERK/MAPK, p38/MAPK, JNK/MAPK, and AKT protein kinase signaling pathways were upregulated in a C5aR-dependent manner. These results demonstrate an apoptotic effect and cellular signaling effect of high-dose C5a. Taken together, the overall data suggest that high levels of C5a may play a role in C5aR-dependent apoptosis of adrenal medullary cells in sepsis.

The Role of Omentin-1 and Fibroblast Growth Factor-23 in Iraqi Patients with Prostate Cancer during Chemotherapy

Background: Omentin-1 is mainly expressed in stromal vascular cells of adipose tissue and can also be expressed in airway goblet cells, mesothelial cells, and vascular cells. Fibroblast growth factor 23 (FGF-23), generated by bone cells, regulates phosphate and vitamin D metabolism by regulating phosphate reabsorption in the kidneys and inhibiting vitamin D activation. Vitamin D is a fat-soluble vitamin that regulates calcium absorption, bone health, and immunological function. Prostate cancer is a significant health concern for men worldwide. Several studies demonstrated a link between these variables and cancer as they exert important anti-inflammatory, antioxidative, and anti-cancer functions. Objectives: To assess the impact of Omentin and FGF-23 biochemical functions, as well as the anti-cancer properties of vitamin D. Subjects and methods: This is a case-control study on serum samples collected from Iraqi prostate cancer patients after receiving chemotherapy at Al Amal Center in Imam Hussein Medical City in Karbala between November 2022 to May 2023. The serum samples were collected from two groups: control group consisted of 30 healthy males. Patient group consisted of 30 prostate cancer patients after receiving chemotherapy, both groups aged 45 – 80 years. The two groups were matched for body mass index. ELISA technology was used to estimate serum levels of the aforementioned biochemical parameters with vitamin D. Results: patient group had a significantly higher FGF-23 level than control group (309.5±41.65) versus (163.1±22.4) (p&lt;0.001). On the other hand, Irisin, Omentin and Vitamin D mean serum concentrations were significantly lower in-patient group (15.2±4.24), (13.8±4.28) and (4.4±0.69) (p&lt;0.001), respectively, compared to control group (60.8±3.5), (38.8±6.59), and (18.9±2.36), respectively. (ROC) curve analysis identified the best AUC values of FGF-23, Omentin, and Vitamin D (0.995, 0.959, 0.937), respectively, which suggests a high level of accuracy. Conclusions: These parameters may serve as critical indicators for prostate cancer patients and their disease progress. Vitamin D insufficiency is a risk factor for these individuals.

Microalgae as feed additives in poultry: A review on the health-promoting effects

This review explores the effects of the inclusion of microalgal biomass in feed on the health of poultry (broilers and laying hens). Microalgae have emerged as a promising feed additive, valued not only for their rich nutritional profile, but also for their bioactive substances. Bioactive compounds, such as phenolics, polyunsaturated fatty acids, oligosaccharides and carotenoids, exhibit antioxidant, anti-inflammatory, antibacterial, and antiviral functions, which hold promise for promoting poultry health. With the ban on prophylactic antibiotic use in feed, microalgal biomass emerges as an innovative feed additive to enhance growth performance and prevent health issues in poultry. This review extensively explains the critical health parameters of poultry, including histology of the intestinal tract, intestinal permeability, immunity, antioxidant status and prebiotic effects on the intestinal microbiome. Furthermore, it offers valuable insights into the inclusion of microalgae in poultry feed, promoting these health parameters. It concludes with suggestions for further research and practical recommendations on how to improve poultry health using microalgal biomass.

Identification of functional heterogeneity of immune cells and tubular-immune cellular interplay action in diabetic kidney disease.

Renal inflammation plays key roles in the pathogenesis of diabetic kidney disease (DKD). Immune cell infiltration is the main pathological feature in the progression of DKD. Sodium glucose cotransporter 2 inhibitor (SGLT2i) were reported to have antiinflammatory effects on DKD. While the heterogeneity and molecular basis of the pathogenesis and treatment with SGLT2i in DKD remains poorly understood. To address this question, we performed a single-cell transcriptomics data analysis and cell cross-talk analysis based on the database (GSE181382). The single-cell transcriptome analysis findings were validated using multiplex immunostaining. A total of 58760 cells are categorized into 25 distinct cell types. A subset of macrophages with anti-inflammatory potential was identified. We found that Ccl3+ (S100a8/a9 high) macrophages with anti-inflammatory and antimicrobial in the pathogenesis of DKD decreased and reversed the dapagliflozin treatment. Besides, dapagliflozin treatment enhanced the accumulation of Pck1+ macrophage, characterized by gluconeogenesis signaling pathway. Cell-cross talk analysis showed the GRN/SORT1 pair and CD74 related signaling pathways were enriched in the interactions between tubular epithelial cells and immune cells. Our study depicts the heterogeneity of macrophages and clarifies a new possible explanation of dapagliflozin treatment, showing the metabolism shifts toward gluconeogenesis in macrophages, fueling the anti-inflammatory function of M2 macrophages, highlighting the new molecular features and signaling pathways and potential therapeutic targets, which has provided an important reference for the study of immune-related mechanisms in the progression of the disease.

Dietary curcumin supplementation enhances growth performance and anti-inflammatory functions by modulating gut microbiota, microbiota-derived metabolites, and expression of inflammation-related genes in broilers.

Curcumin (CUR) is a natural polyphenolic substance that has been widely used since ancient times for its multiple beneficial functions. However, whether CUR affects growth performance of broilers by altering gut microbiota and metabolite and the underlying mechanism are largely unknown. This study was conducted to evaluate the effect of dietary CUR supplementation on growth performance, anti-inflammatory function, intestinal morphology and barrier, cecum microbiota and metabolite profile of broilers. Sixty 1-day-old male broilers were randomly divided into control group (CON, fed a control diet) and CUR group (fed a control diet supplemented with 200mg/kg CUR) after 2 days of adaptation. Results showed that after feeding to 52-day-old, compared with CON broilers, the CUR broilers showed improved feed utilization efficiency and growth performance. Furthermore, the CUR broilers showed an improved intestinal morphology, which was demonstrated by a lower crypt depth in the jejunum. The 16S rRNA gene sequencing and non-targeted metabonomics (LC-MS/MS) analysis results showed that the cecum microbiota ecology and function were significantly improved, and the abundance of beneficial flora and metabolites were increased, while the harmful bacteria and metabolites were significantly decreased. In addition, RT-qPCR results showed that CUR significantly reduced inflammatory responses, promoted the formation of the mucosal barrier and enhanced digestion, absorption and transport of lipids and glucose related genes expression in the intestine. These above findings demonstrated that dietary CUR supplementation improved growth performance, intestinal morphology and anti-inflammatory functions, mainly by manipulating cecum microbiota and microbiota-derived metabolites, which provides a credible explanation for the growth-promoting effect and anti-inflammatory functions of CUR and aids our understanding of the mechanisms underlying.

Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) are chronic immune-mediated diseases which primarily target the intestines. In recent years, the development and regulatory approval of various immunotherapies, both biological agents and small molecules, that target specific pathways of the IBD-associated inflammatory cascade have revolutionized the treatment of IBD. Small molecules offer the advantages of oral administration and short wash-out times. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of ceramide, which exerts its functions after binding to five G-protein-coupled receptors (S1PR1-S1PR5). Concerning IBD, S1P participates in the egress of lymphocytes from the secondary lymphoid tissue and their re-circulation to sites of inflammation, mainly through S1PR1 binding. In addition, this system facilitates the differentiation of T-helper cells towards proinflammatory immunophenotypes. Recently, S1P modulators have offered a valuable addition to the IBD treatment armamentarium. They exert their anti-inflammatory function via sequestration of T cell subsets in the lymphoid tissues and prevention of gut homing. In this review, we revisit the role of the S1P/S1PR axis in the pathogenesis of IBD and discuss efficacy and safety data from clinical trials and real-world reports on the two S1PR modulators, ozanimod and etrasimod, that are currently approved for IBD treatment, and comment on their potential positioning in the IBD day-to-day management. We also present recent data on emerging S1P modulators. Finally, based on the successes and failures of S1PR modulators in IBD, we discuss future avenues of IBD treatments targeting the S1P/S1PR axis.