In vitro and in vivo immunomodulatory activity of sulfated polysaccharide from Porphyra haitanensis

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

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The immunomodulatory activity of SerpinB3 an protease-inhibitor in vivo and in vitro

Digestive and Liver Disease ◽

10.1016/j.dld.2017.01.056 ◽

2017 ◽

Vol 49 (1) ◽

pp. e26

Author(s):

A. Cappon ◽

G. Villano ◽

S. Quarta ◽

A. Biasiolo ◽

C. Turato ◽

...

Keyword(s):

Protease Inhibitor ◽

Immunomodulatory Activity

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A novel antioxidant sulfated polysaccharide from the algae Gracilaria caudata: In vitro and in vivo activities

Food Hydrocolloids ◽

10.1016/j.foodhyd.2018.12.007 ◽

2019 ◽

Vol 90 ◽

pp. 28-34 ◽

Cited By ~ 21

Author(s):

Poliana O. Cavalcante Alencar ◽

Glauber C. Lima ◽

Francisco Clark N. Barros ◽

Luís E.C. Costa ◽

Carla Vivianne P.E. Ribeiro ◽

...

Keyword(s):

Sulfated Polysaccharide

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Anticoagulant Properties of a Green Algal Rhamnan-type Sulfated Polysaccharide and Its Low-molecular-weight Fragments Prepared by Mild Acid Degradation

Marine Drugs ◽

10.3390/md16110445 ◽

2018 ◽

Vol 16 (11) ◽

pp. 445 ◽

Cited By ~ 7

Author(s):

Xue Liu ◽

Peng Du ◽

Xiao Liu ◽

Sujian Cao ◽

Ling Qin ◽

...

Keyword(s):

Molecular Weight ◽

Anticoagulant Activity ◽

Sulfated Polysaccharide ◽

Low Molecular Weight ◽

Thrombin Time ◽

Acid Degradation ◽

Molecular Weights ◽

Green Algal

The active sulfated polysaccharide from seaweed possesses important pharmaceutical and biomedical potential. In the study, Monostroma sulfated polysaccharide (MSP) was obtained from Monostroma angicava, and the low-molecular-weight fragments of MSP (MSP-Fs: MSP-F1–MSP-F6) were prepared by controlled acid degradation. The molecular weights of MSP and MSP-F1–MSP-F6 were 335 kDa, 240 kDa, 90 kDa, 40 kDa, 24 kDa, 12 kDa, and 6.8 kDa, respectively. The polysaccharides were sulfated rhamnans that consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ units with partial sulfation at C-2 of →3)-α-l-Rhap-(1→ and C-3 of →2)-α-l-Rhap-(1→. Anticoagulant properties in vitro of MSP and MSP-F1–MSP-F6 were evaluated by studying the activated partial thromboplastin time, thrombin time, and prothrombin time. Anticoagulant activities in vivo of MSP and MSP-F4 were further evaluated; their fibrin(ogen)olytic activities in vivo and thrombolytic properties in vitro were also assessed by D-dimer, fibrin degradation products, plasminogen activator inhibitior-1, and clot lytic rate assays. The results showed that MSP and MSP-F1–MSP-F4 with molecular weights of 24–240 kDa had strong anticoagulant activities. A decrease in the molecular weight of MSP-Fs was accompanied by a decrease in the anticoagulant activity, and higher anticoagulant activity requires a molecular weight of over 12 kDa. MSP and MSP-F4 possessed strong anticoagulant activities in vivo, as well as high fibrin(ogen)olytic and thrombolytic activities. MSP and MSP-F4 have potential as drug or helpful food supplements for human health.

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Sulfated polysaccharide isolated from Globularia alypum L.: Structural characterization, in vivo and in vitro anticoagulant activity, and toxicological profile

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2018.11.044 ◽

2019 ◽

Vol 123 ◽

pp. 335-342 ◽

Cited By ~ 5

Author(s):

Zohra Ghlissi ◽

Fatma Krichen ◽

Rim Kallel ◽

Ikram Ben Amor ◽

Tahiya Boudawara ◽

...

Keyword(s):

Structural Characterization ◽

Anticoagulant Activity ◽

Sulfated Polysaccharide ◽

Globularia Alypum ◽

Toxicological Profile

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766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs)

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.766 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A801-A801

Author(s):

Sachin Bhagchandani ◽

Lauren Milling ◽

Bin Liu ◽

Timothy Fessenden ◽

Stefani Spranger ◽

...

Keyword(s):

Survival Rates ◽

Immunomodulatory Activity ◽

Systemic Delivery ◽

Antibody Treatment ◽

Tlr Agonists ◽

Cytokine Levels ◽

Systemic Side Effects ◽

Tolerable Dose

BackgroundAlthough toll-like receptor (TLR) agonists such as imidazoquinoline derivatives (IMDs) have been well researched and are FDA approved as topical solutions for treatment of skin cancer, their systemic delivery for treatment of metastatic disease has not been successful due to toxicity issues. Therefore, to lessen the degree of the adverse effects of intravenous delivery of IMDs such as resiquimod (R848), a bottlebrush prodrug (BPD) system enabling controlled release of R848 at tunable rates was designed and synthesized. We hypothesized that this approach would allow for minimizing the release of the free drug in serum, allowing for a higher concentration to accumulate in the tumor while minimizing systemic side effects.MethodsR848 was conjugated to a bottlebrush polymer with different linkers designed to precisely tune the R848 release rate. The release rates of the drug delivered through this system were first tested in PBS. These prodrug formulations were validated for drug activity in vitro in mouse and human TLR reporter cells. The maximum tolerable dose was defined by monitoring weight loss and serum cytokine levels upon intravenous administration at multiple concentrations. Finally, anti-tumor efficacy of the BPD system was tested in vivo using the MC38 colon cancer model as a monotherapy and in combination with anti-PD-1 antibody treatment.ResultsThe in-vitro half-lives of the conjugated drugs varied from a few days to over a month when tested in PBS. The different BPDs demonstrated linker dependent TLR activation upon culturing with TLR reporter cells validating the immunomodulatory activity of R848. It was found that the R848-BPDs, which accumulated at the tumor site over time, significantly delayed tumor growth and improved survival rates, which was further enhanced when used in combination with anti-PD-1.ConclusionsOverall, our research suggests that our R848-BPD platform allows for safe, systemic delivery of TLR agonists to activate the immune system in treatment of cancer.

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Evaluation of The Antioxidant, Antidiabetic and Immunomodulatory Activity of Cydonia oblonga Fruit Extract

Chiang Mai University Journal of Natural Sciences ◽

10.12982/cmujns.2021.052 ◽

2021 ◽

Vol 20 (3) ◽

Author(s):

Fatma Zahra Sakhri ◽

Sakina Zerizer ◽

Chawki Bensouici

Keyword(s):

Free Radicals ◽

Cation Radical ◽

Antidiabetic Activity ◽

Immunomodulatory Activity ◽

Ferrous Ions ◽

Cydonia Oblonga ◽

Innate Defense ◽

Hydroethanolic Extract

Dietary natural antioxidant consumption can protect the human body from several diseases induced by free radicals. The aim of this study was to evaluate the antioxidant, antidiabetic and immunomodulatory properties of Cydonia oblonga fruit. For this; hydroethanolic extract of Cydonia oblonga fruit (HECO) was examined for antioxidant activity using DPPH free radical sc avenging, ABTS cation radical decolorization, Cupric reducing antioxidant capacity (CUPRAC), and Metal Chelating on ferrous ions activities. The inhibitory activity of the extract against α-glucosidase enzyme was also investigated. HECO was tested in vivo for the immunomodulatory activity on non-specific immunity by the carbon clearance test. The content of the nonenzymatic antioxidant reduced glutathione (GSH) in liver tissue of used mice was estimated. in vitro studies revealed that the HECO has an inhibitory concentration (IC50) value of 249.26 ± 3.75μg/mL, 117.34 ± 1.41 μg/ml for DPPH and ABTS scavenging activity respectively. As well as the ability to reduce cupric (167.17 ± 1.15μg/mL) and iron (Fe) (417.98 ± 48.82μg/mL). The extract showed antidiabetic activity as evidenced by its capacity to inhibit the α-glucosidase enzyme (IC50: 326.48 ± 18.56 µg/mL) near the acarbose (IC50: 275.98 ± 1.57 µg/mL) used as a positive control. In addition, our results showed that HECO at the concentration of 50 and 100 mg/kg significantly increased the clearance rate of carbon from the bloodstream concomitant with increased liberation of GSH from liver cells. This study demonstrates that HECO is effective in scavenging free radicals and can serve as potent antioxidants that provide potential treatment and prevention for diabetes with benefits on the innate defense system. Keywords: Antidiabetic, Antioxidant, Cydonia oblonga, Hydroethanolic extract, Phagocytic activity

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Immunomodulatory activity of IR700-labelled affibody targeting HER2

Cell Death and Disease ◽

10.1038/s41419-020-03077-6 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Justyna Mączyńska ◽

Chiara Da Pieve ◽

Thomas A. Burley ◽

Florian Raes ◽

Anant Shah ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Light Irradiation ◽

Immunomodulatory Activity ◽

Her2 Positive ◽

Immunological Responses ◽

Cancer Cell Death ◽

Immature Dendritic Cells

Abstract There is an urgent need to develop therapeutic approaches that can increase the response rate to immuno-oncology agents. Photoimmunotherapy has recently been shown to generate anti-tumour immunological responses by releasing tumour-associated antigens from ablated tumour cell residues, thereby enhancing antigenicity and adjuvanticity. Here, we investigate the feasibility of a novel HER2-targeted affibody-based conjugate (ZHER2:2395-IR700) selectively to induce cancer cell death in vitro and in vivo. The studies in vitro confirmed the specificity of ZHER2:2395-IR700 binding to HER2-positive cells and its ability to produce reactive oxygen species upon light irradiation. A conjugate concentration- and light irradiation-dependent decrease in cell viability was also demonstrated. Furthermore, light-activated ZHER2:2395-IR700 triggered all hallmarks of immunogenic cell death, as defined by the translocation of calreticulin to the cell surface, and the secretion of ATP, HSP70/90 and HMGB1 from dying cancer cells into the medium. Irradiating a co-culture of immature dendritic cells (DCs) and cancer cells exposed to light-activated ZHER2:2395-IR700 enhanced DC maturation, as indicated by augmented expression of CD86 and HLA-DR. In SKOV-3 xenografts, the ZHER2:2395-IR700-based phototherapy delayed tumour growth and increased median overall survival. Collectively, our results strongly suggest that ZHER2:2395-IR700 is a promising new therapeutic conjugate that has great potential to be applicable for photoimmunotherapy-based regimens.

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