Immune Regulatory Activities Research Articles

The Potential Effectiveness of an Ancient Chinese Herbal Formula Yupingfeng-San for Prevention of COVID-19: A Systematic Review

The COVID-19 has been spreading all over the world, and human health is at stake. Conventional medicine played an important role in the treatment and syndrome relief, while there is limited research evidence to support any prevention or antiviral treatment for COVID-19. YupingfengSan is a classic formula with the effect of replenishing qi, consolidating exterior, and arresting sweating. YupingfengSan has been widely used to treat various diseases in China and Southeast Asia for hundreds of years. Accumulating evidence suggests that YPFS has both immune-regulatory and anti-virus effects clinically, but leaving the mechanism elusive. In this paper, we reviewed the recent progress of YupingfengSan in immune-regulatory and anti-virus activities, including the effect on mucosal immunity, biological antagonism, macrophages, adaptive immunity, and NK cells. From this systematic review, we speculate that YPFS can play an effective role in the prevention of SARS-CoV-2, but further experimental studies are expected to investigate the specific mechanisms. This review suggests an alternative direction for the prevention of COVID-19.

Effect of Amygdalin on Murine Melanoma Cancer Cell Line and Normal Human Fibroblast Cells

Background and Objectives: Melanoma is the most aggressive and fatal type of skin cancer caused by the uncontrolled proliferation of melanocytes. The ineffectiveness of existing therapies has encouraged researchers to use herbal medicines. Amygdalin is a natural cyanogenic glycoside that is found in fruits and seeds of different plants and has antiproliferative, antioxidant, and immune-regulating activities. In this study, we aim to evaluate the effect of amygdalin against murine melanoma cancer cell line and normal human fibroblast cells. Methods: The murine melanoma cancer cell line (B16F10) and human foreskin fibroblasts (HFF) cells were exposed to different concentrations of amygdalin and dacarbazine (a standard anticancer drug) for 24 and 48 hours. The half-maximal inhibitory concentration (IC50) of amygdalin was obtained using the MTT assay and analyzed in GraphPad Prism and Excel applications. Results: Amygdalin had a high cytotoxic effect on the melanoma cell line within 48 hours of exposure, which is comparable to the cytotoxicity of dacarbazine at the same time. Amygdalin had no cytotoxic effect on HFF cells, while dacarbazine caused a high toxicity on HFF cells. Conclusion: Amygdalin, by inhibiting the proliferation of cancer cells in a dose-dependent manner, may prevent the adverse effects of chemical drugs on healthy cells and can be an appropriate treatment option for melanoma.

Bruton's tyrosine kinase inhibition suppresses pathological retinal angiogenesis.

Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1-knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis.

Adaptive copy number variations of ancient prokaryotic genes in marine fish colonization

During extensive evolution, higher eukaryotes have acquired numerous prokaryotic genes, some of which have experienced adaptive copy number variations (CNVs) in response to changing environments. The specific contribution of ancient prokaryotic genes to the evolutionary dynamics of marine fish remains unclear. In this study, we investigated ancient prokaryotic genes in 33 freshwater and 14 non-freshwater fish species. Non-freshwater fish exhibited a higher proportion of these genes (25.84 %) compared to freshwater fish (17.66 %), though functional categories showed similarity, suggesting genetic conservation. Comprehensive CNV analysis identified 24 genes with significantly higher copy numbers in non-freshwater fish, enriched in glycerolipid metabolism, immune regulation, and catechol O-methyltransferase activity. Eight of these genes displayed increased copy numbers in marine populations compared to Asian freshwater populations. These findings indicate that CNVs in genes related to glycerolipid metabolism, immune regulation, and methyltransferase activity may play crucial roles in marine adaptation at global and regional evolutionary scales.

Poricoic acid a ameliorates high glucose-induced podocyte injury by regulating the AMPKα/FUNDC1 pathway.

Poricoic acid A (PAA), a major triterpenoid component of Poria cocos with anti-tumor, anti-fibrotic, anti-inflammatory, and immune-regulating activities, has been shown to induce podocyte autophagy in diabetic kidney disease (DKD) by downregulating FUN14 domain containing 1 (FUNDC1). This study aimed to identify the role of adenosine monophosphate-activated protein kinase alpha (AMPKα) in PAA-mediated phosphorylation of FUNDC1 in podocyte injury occurring in the pathogenesis of DKD. A cellular model of renal podocyte injury was established by culturing MPC5 cells under high-glucose (HG) conditions. MPC5 cells were subjected to transfection with small interfering RNA (siRNA) targeting AMPKα or siRNA targeting FUNDC1, an AMPKα activator, or PAA. PAA treatment induced the phosphorylation of AMPKα in HG-cultured podocytes. AMPKα activation was implicated in the inhibitory effect of PAA on FUNDC phosphorylation in HG-cultured podocytes. Treatment targeting the AMPKα activator also significantly augmented proliferation, migration, mitochondrial membrane potential, and autophagy levels, while reducing apoptosis levels, inhibiting oxidative stress, and suppressing the release of proinflammatory factors in HG-cultured MPC5 cells. In contrast, insufficient expression of AMPKα reversed the effects of PAA on the proliferation, migration, and apoptosis of podocytes and further exacerbated the reduction of phosphorylated FUNDC1 expression in podocytes under HG conditions. AMPKα is involved in the regulation of FUNDC1 phosphorylation by PAA in HG-induced podocyte injury. Furthermore, the AMPKα/FUNDC1 pathway plays a crucial regulatory role in HG-induced podocyte injury. These findings support AMPKα, FUNDC1, and the AMPKα/FUNDC1 pathway as targets for PAA intervention.

Quantitative Changes and Transformation Mechanisms of Saponin Components in Chinese Herbal Medicines during Storage and Processing: A Review.

Saponins are an important class of active components in Chinese herbal medicines (CHMs), which are present in large quantities in Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, Polygonati Rhizoma, etc., and have immune regulation, anti-tumor, anti-inflammatory, anti-cardiovascular disease, and hypoglycemic activities. Storage and processing are essential processes in the production process of CHMs which affect the stability of saponin components and then reduce the medicinal and economic value. Therefore, it is of great importance to investigate the effects of storage and processing conditions on the content of saponin components in CHMs. In this paper, the effects of various storage and processing factors, including temperature, pH, enzymes, meta lions, extraction methods, etc., on the saponin content of CHMs are investigated and the underlying mechanisms for the quantitative changes of saponin are summarized. These findings may provide technical guidance for the production and processing of saponin-rich CHMs.

Immune regulatory and anti-resorptive activities of tanshinone IIA sulfonate attenuates rheumatoid arthritis in mice.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and painful joint destruction. Current treatments are helpful in RA remission, but strong immunosuppressive activity and patient resistance are clinical issues. This study explores a dual-action inhibitor, possessing both anti-inflammatory and anti-resorptive properties, as a novel treatment for RA. Therapeutic efficacy and mechanisms of ectosteric (tanshinone IIA sulfonate [T06]) and active site-directed (odanacatib [ODN]) inhibitors of cathepsin K (CatK) were evaluated in RA mouse models. Pathology was assessed through biochemical analyses and histopathological examination. Flow cytometry analysis was performed to characterize immune cells. Anti-inflammatory effects of T06 on nuclear factor kappa beta (NF-κB) pathway were studied in macrophages. T06 effectively lowered the number of joint-resident immune cells, accompanied by significantly reduced production of inflammatory cytokines and collagenolytic proteases. This also included the suppression of Th17 cells and IL-17, resulting in the reduction of osteoclasts in arthritic joints and amplification of the overall anti-resorptive effect of T06, which has been attributed to its selective inhibition of the collagenolytic activity of CatK by preventing its oligomerization. The anti-inflammatory mechanism of T06 was based on blocking the phosphorylation of IκBα in the NF-κB pathway, resulting in reduced activation and expression of inflammatory cytokines. In contrast, ODN had no effect on inflammation and disease progression and was limited to the inhibition of CatK. The combined anti-resorptive and anti-inflammatory activities characterize T06 as a novel therapeutic agent for RA.

Botanical Bioflavonoid Composition from Scutellaria baicalensis- and Acacia catechu-Protected Mice against D-Galactose-Induced Immunosenescence, and Cyclophosphamide Induced Immune Suppression.

Oxidative stress and chronic inflammation create a perpetual cycle in the elderly, where impaired immune function amplifies susceptibility to oxidative damage, and oxidative stress further weakens the immune response. This cycle is particularly detrimental to the respiratory system of the elderly, which is an easy target for constant exogenous harmful attacks during cold/flu season or under heavy air pollution. Herbal medicines that protect respiratory function are seen as safer alternatives to conventional therapies; however, there is limited availability of scientifically validated, safe, and effective natural supplements for these conditions. In this study, we evaluated a standardized bioflavonoid composition, UP446, that contains bioactives from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu as a natural and nutritional supplement for its antioxidative and immunoregulatory effects in oxidative stress-accelerated aging and chemically induced immune suppression mouse models. Immunosenescence was induced through the repeated subcutaneous inoculation of D-galactose (D-Gal) at a dose of 500 mg/kg/day in CD-1 mice. UP446 was administered orally at doses of 100 mg/kg and 200 mg/kg starting in the fifth week of immunosenescence induction. This study lasted a total of ten weeks. All mice received a quadrivalent influenza vaccine 2 weeks before termination. Whole blood, serum, spleen homogenate, and thymus tissues were processed for analysis. Cyclophosphamide (Cy)-induced immunosuppression was triggered by three consecutive injections of cyclophosphamide at 80 mg/kg/day, followed by the oral administration of UP446 for 18 days at doses of 100 mg/kg and 200 mg/kg. Blood was collected from each animal at necropsy, and serum was isolated for IgA and IgG ELISA analysis. UP446 was found to improve immune response, as evidenced by the stimulation of innate (NK cells) and adaptive immune responses (T cells and cytotoxic T cells), an increase in antioxidant capacity (glutathione peroxidase), the preservation of vital immune organs (the thymus), and a reduction in NFκB. UP446 also increased serum levels of IgA and IgG. The findings presented in this report demonstrate the antioxidative, anti-inflammatory, and immune-regulatory activities of UP446, suggesting its potential use in respiratory conditions involving immune stress due to aging, oxidative stress, and/or pathogenic challenges.

Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

Pharmacological actions of the bioactive compounds of Epimedium on the male reproductive system: current status and future perspective.

Compounds isolated from Epimedium include the total flavonoids of Epimedium, icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium, its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.

Research progress of Gastrodia elata Blume polysaccharides: a review of chemical structures and biological activities.

Gastrodia elata Blume (G. elata), listed as one of the 34 precious Chinese medicines, servers a dual purpose as both a medicinal herb and a food source. Polysaccharide is the main active ingredient in G. elata, which has pharmacological activities such as immune regulation, anti-oxidation, anti-cancer, anti-aging, neuroprotection and antibacterial activity and so on. The biological activities of G. elata polysaccharide (GPs) is closely related to its chemical structures. However, no a review has synthetically summarized the chemical structures and pharmacological activities of GPs. This study delves into the chemical structures, pharmacological action of GPs, offering insights for the future development an application of these compounds.

Ascites-derived hsa-miR-181a-5p serves as a prognostic marker for gastric cancer-associated malignant ascites

BackgroundPeritoneal carcinomatosis was the main reason leading to gastric cancer (GC)-related death. We aimed to explore the roles of dysregulated microRNAs (miRNAs) and related immune regulation activities in GC-associated malignant ascites.MethodsGSE126399 were downloaded from GEO database. Differentially expressed miRNAs in GC ascites samples was firstly screened, and critical miRNAs were further investigated by LASSO (least absolute shrinkage and selection operator) logistic regression and random forest (RF) algorithm. Receiver operating characteristic of critical miRNAs was also constructed. Moreover, functional analysis, immune cell infiltration associated with differentially expressed mRNAs were further analyzed. After selecting key modules by weighted gene co-expression network analysis, mRNAs related with survival performance and transcription factor (TF)-miRNA-mRNA network were constructed.ResultsHsa-miR-181b-5p was confirmed as critical differentially expressed miRNAs in GC ascites. Then, the tumor samples were divided into high- and low- expression groups divided by mean expression levels of hsa-miR-181b-5p, and subjects with high hsa-miR-181b-5p levels had better survival outcomes. In total, 197 differentially expressed mRNAs associated with hsa-miR-181b-5p levels were obtained, and these mRNAs were mainly enriched in muscle activity and vascular smooth muscle contraction. Hsa-miR-181b-5 was positively related with activated CD4 T cells and negatively related with eosinophil. 17 mRNAs were selected as mRNAs significantly related with prognosis of GC, such as PDK4 and RAMP1. Finally, 75 TF-miRNA-mRNA relationships were obtained, including 15 TFs, hsa-miR-181b-5p, and five mRNAs.ConclusionOur data suggest that the differentially expressed hsa-miR-181b-5p in ascites samples of GC patients may be a valuable prognostic marker and a potential target for therapeutic intervention, which should be validated in the near future.

Structural characterization and innate immunomodulatory effect of glucomannan from Bletilla striata

The crude polysaccharide of Bletilla striata in this study was extracted by water extraction and alcohol precipitation and further purified by gel column to yield the purified component Bletilla striata polysaccharide (BSP). Its structure and innate immune regulation activity were studied. BSP mainly comprises mannose and glucose, with a monosaccharide molar ratio of 2.9:1 and a weight-average molecular weight of 28,365 Da. It is a new low-molecular-weight water-soluble neutral glucomannan. BSP contains a → 6)-β-Manp-(1→, →4)-β-Glcp-(1→, →4)-β-Manp-(1 → and →3)-α-Manp-(1 → linear main chain, containing β-Glcp-(1 → and β-Manp-(1 → two branched chain fragments were connected to the Man residue at position 4. BSP can enhance the anti-infection ability of Caenorhabditis elegans against Pseudomonas aeruginosa, significantly improve the phagocytic ability of RAW264.7 macrophages, stimulate the secretion of NO and TNF-α, and have good innate immune regulation activity. These findings guide the use of Bletilla striata polysaccharides with immunomodulatory action.

Mechanisms of Laser Acupuncture – Hypotheses and Evidence

Laser acupuncture, a rising complementary therapy, applies a low-intensity laser to acupuncture points, yet its underlying mechanisms remain unclear. Proposed hypotheses include modulation of cellular signaling, tissue repair, and immune modulation. Laser acupuncture may stimulate energy flow, neurotransmitter release, cellular changes, immune regulation, and neuroendocrine activity. Additionally, the biophoton theory suggests an involvement of ultra-weak photon radiation from cells. Litscher et al. explore these mechanisms through neurophysiological analysis, biochemical measurements, imaging techniques, and clinical trials. They documented subtle human brain responses following laser stimulation, potentially modulating the ascending reticular activating system. However, further research is needed to validate and expand these findings for broader clinical application of laser acupuncture.

Antioxidant and Anti-Fatigue Effects of a Standardized Botanical Extract Fraction (HemoHIM) in Forced-Exercised Aged Mice.

HemoHIM is a standardized medicinal herbal preparation consisting of extracts of Angelica gigas Nakai, Cnidium officinale Makino, and Paeonia lactiflora Pallas that possesses immune regulatory activities. This study aimed to research the potential antioxidant effects of HemoHIM and its capacity for reducing fatigue in aged mice subjected to forced exercise. After administering HemoHIM 125 (500 mg/kg orally) for 4 weeks in 8-month-old female C57BL/6 mice (4 groups of 10 mice), various parameters were evaluated. The analyses revealed that HemoHIM enhanced swimming time and grip strength. In addition, it significantly reduced serum lactate levels and increased liver glutathione peroxidase (GPx) levels after exercise challenge. The expression levels of antioxidant enzymes and factors, including nuclear factor erythroid 2-related factor-2 (Nrf-2), heme oxygenase 1, superoxide dismutase, GPx, and glutathione reductase, were significantly higher in liver and muscle tissues of mice treated with HemoHIM. These results indicate that HemoHIM might function as an anti-fatigue and antioxidant agent by modulating the Nrf-2 signaling pathway.

Advances in research on the anti-tumor mechanism of Astragalus polysaccharides.

The dry root of the soybean plant Astragalus membranaceus (Fisch) Bge. var. mongholicus (Bge) Hsiao or A. membranaceus (Fisch) Bge, Astragali Radix (AR) has a long medicinal history. Astragalus polysaccharide (APS), the natural macromolecule that exhibits immune regulatory, anti-inflammatory, anti-tumor, and other pharmacological activities, is an important active ingredient extracted from AR. Recently, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosis. In addition, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body's immunity. This macromolecule has prospects for broad application in tumor therapy through various pathways. In this article, we present the latest progress in the research on the anti-tumor effects of APS and its underlying mechanisms, aiming to provide novel theoretical support and reference for its use in cancer therapy.

The King of Chinese Medicine——Glycyrrhiza glabra (Licorice): All-round Inquiry in its Chemical Composition, Pharmacodynamics, Traditional and Medicinal Value

Licorice, a perennial herb of Leguminosa, is one of the oldest and most widely used herbal medicines worldwide. Its distinct sweet flavor and rich medicinal value make it an integral component of traditional Chinese medicine (TCM) formulations, which continue to be widely employed. The main chemical constituents of licorice include triterpenoid saponins, flavonoids, and polysaccharides. Experimental and clinical studies have demonstrated that various extracts and pure compounds derived from licorice exhibit a wide range of pharmacological properties including anti-inflammatory, antioxidant, antimicrobial, antiviral, antitumor, immune-regulatory, and neuroprotective activities. The bioactive constituents of licorice offer therapeutic benefits for cardiovascular and cerebrovascular diseases, diabetes mellitus, and liver disorders. This comprehensive review discusses the primary chemical constituents of licorice and their pharmacological activities, describes in vivo and in vitro models employed for studying licorice, and its potential targets and mechanisms of action. Furthermore, we discuss the toxicological profile, side effects, dosage recommendations, and clinical applications of licorice. This review aims to establish a foundation for further research on the safe and effective utilization of licorice while facilitating an in-depth exploration of its properties and fostering the development of novel therapeutic agents. Graphical abstract: http://links.lww.com/AHM/A102

VqNAC44 enhances stilbene synthesis and disease resistance in Chinese wild grape by interacting with VqMYB15

As significant phytoalexins, stilbene compounds can improve the stress resistance of grapes under biotic and abiotic stress conditions and have biological effects such as antitumour, antioxidant, immune regulation and cardiovascular protection activities in humans. RESVERATROL SYNTHASE (RS), also known as STILBENE SYNTHASE (STS), is the critical enzyme regulating stilbene synthesis and has been identified in a few plant species. However, the regulatory mechanisms of stilbene synthesis are uncertain. In this study, an NAC family transcription factor from Vitis quinquangularis, named VqNAC44, was characterized as an indirect regulator of stilbene synthesis. It is worth noting that VqNAC44 did not bind to the STS promoter nor did it interact with the STS protein but interacted with the MYB transcription factor VqMYB15. This interaction between VqMYB15 and VqNAC44 was validated by a yeast two-hybrid assay and bimolecular fluorescence complementation. Overexpressing VqNAC44 in Arabidopsis thaliana significantly increased its tolerance to biotic and abiotic stresses. Transient overexpression of VqNAC44 and VqMYB15 in grape leaves resulted in increased expression of the STS gene and increased production of stilbene compounds. The experimental results confirmed that VqNAC44 regulated stilbene synthesis by interacting with VqMYB15, thereby enhancing the plant stress resistance.

In vitro inhibition of Pseudomonas aeruginosa PAO1 biofilm formation by DZ2002 through regulation of extracellular DNA and alginate production.

Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen associated with biofilm infections, which can lead to persistent infections. Therefore, there is an urgent need to develop new anti-biofilm drugs. DZ2002 is a reversible inhibitor that targets S-adenosylhomocysteine hydrolase and possesses anti-inflammatory and immune-regulatory activities. However, its anti-biofilm activity has not been reported yet. Therefore, we investigated the effect of DZ2002 on P. aeruginosa PAO1 biofilm formation by crystal violet staining (CV), real-time quantitative polymerase chain reaction (RT-qPCR) and confocal laser scanning microscopy (CLSM). The results indicated that although DZ2002 didn't affect the growth of planktonic PAO1, it could significantly inhibit the formation of mature biofilms. During the inhibition of biofilm formation by DZ2002, there was a parallel decrease in the synthesis of alginate and the expression level of alginate genes, along with a weakening of swarming motility. However, these results were unrelated to the expression of lasI, lasR, rhII, rhIR. Additionally, we also found that after treatment with DZ2002, the biofilms and extracellular DNA content of PAO1 were significantly reduced. Molecular docking results further confirmed that DZ2002 had a strong binding affinity with the active site of S-adenosylhomocysteine hydrolase (SahH) of PAO1. In summary, our results indicated that DZ2002 may interact with SahH in PAO1, inhibiting the formation of mature biofilms by downregulating alginate synthesis, extracellular DNA production and swarming motility. These findings demonstrate the potential value of DZ2002 in treating biofilm infections associated with P. aeruginosa.

Immunological and homeostatic pathways of alpha -1 antitrypsin: a new therapeutic potential.

α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.