Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand.

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}(μ-pydz)]Cl (C1), [{Pt(ibn)Cl}(μ-pydz)]Cl (C2), [{Pt(1,3-pn)Cl}(μ-pydz)]Cl (C3) and [{Pt(1,3-pnd)Cl}(μ-pydz)]Cl (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1-C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis, fluorescence emission spectroscopy and molecular docking.

The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.

Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people.

The Pt(-pr-thiosal)2 and BCL1 Leukemia Lymphoma: Antitumor Activity In Vitro and In Vivo.

B cell malignancies are, despite the development of targeted therapy in a certain percentage of the patients still a chronic disease with relapses, requiring multiple lines of therapy. Regimens that include platinum-based drugs provide high response rates in different B cell lymphomas, high-risk chronic lymphocytic leukemia (CLL), and devastating complication of CLL, Richter's syndrome. The aim of this study was to explore the potential antitumor activity of previously synthetized platinum(IV) complex with alkyl derivatives of thyosalicilc acid, PtCl2(-pr-thiosal)2, toward murine BCL1 cells and to delineate possible mechanisms of action.

Contrasting Roles of the Galectin-3 in the Schizophrenia Onset, Clinical Presentation, and Somatic Comorbidity.

The role of the Galectin-3 (Gal-3) has already been explored in various somatic diseases, considering its engagement in infection, acute and chronic inflammation, and autoimmunity. Additionally, it has been recognized that Gal-3 is included in neuroinflammation and neurodegeneration, so we presented the possibility for its involvement in neuroprogression in schizophrenia. Gal-3 possibly participates in the early life programming of schizophrenia, also in the specific response to viral infections as a "second hit" later in life, and as a part of a unique systemic somatic dysfunction leading to the specific mental changes.

Interleukin-33 pretreatment promotes metastatic growth of murine melanoma by reducing the cytotoxic capacity of CD8 T cells and enhancing regulatory T cells.

Interleukin-33 (IL-33) regulates innate and acquired immune response to pathogens, self-antigens and tumors. IL-33 effects on tumors depend on the dose and mode of administration along with the type of malignancy. We studied the effects of IL-33 on the development of primary and metastatic melanoma induced by B16-F1 cell line in C57BL/6 mice.

The Zn(-pr-thiosal) complex attenuates murine breast cancer growth by inducing apoptosis and G1/S cell cycle arrest.

We investigated the antitumor effects of zinc(II) complex with -propyl thiosalicylic acid [Zn(-pr-thiosal)] in 4T1 murine breast cancer model.  The Zn(-pr-thiosal) complex reduced primary tumor growth and induced tumor cell apoptosis. The Zn(-pr-thiosal) complex disrupted the balance between pro- and antiapoptotic Bcl-2 family members in 4T1 cells and induced G1/S cell cycle arrest.

Conformational analysis and in vitro immunomodulatory and insulinotropic properties of the frog skin host-defense peptide rhinophrynin-27 and selected analogs.

The study investigates conformational analysis and the in vitro cytokine-mediated immunomodulatory and insulin-releasing activities of rhinophrynin-27 (ELRLPEIARPVPEVLPARLPLPALPRN; RP-27), a proline-arginine-rich peptide first isolated from skin secretions of the Mexican burrowing toad Rhinophrynus dorsalis (Rhinophrynidae). In both water and 50% trifluoroethanol-water, the peptide adopts a polyproline type II helical conformation with a high degree of deviation from the canonical collagen-like folding and a pronounced bend in the molecule at the Glu residue. Incubation of mouse peritoneal cells with RP-27 significantly (P < 0.

Deletion of Galectin-3 attenuates acute pancreatitis in mice by affecting activation of innate inflammatory cells.

Acute pancreatitis is characterized by autodigestion of pancreatic cells followed by acute inflammation leading to pathology and death. In experimental acute pancreatitis, pancreatic acinar cells and infiltrating macrophages express Galectin-3 but its role in pathology of this disease is unknown. Therefore, we studied its role using Galectin-3 deficient mice.

Immunomodulatory, insulinotropic, and cytotoxic activities of phylloseptins and plasticin-TR from the Trinidanian leaf frog Phyllomedusa trinitatis.

The aim of the study was to determine the in vitro immunomodulatory, cytotoxic, and insulin-releasing activities of seven phylloseptin-TR peptides and plasticin-TR, first isolated from the frog Phyllomedusa trinitatis. The most cationic peptides, phylloseptin-1.1TR and phylloseptin-3.

Diverse Expression of IL-32 in Diffuse and Intestinal Types of Gastric Cancer.

Introduction: Gastric cancer (GC) represents one of the most common cancers worldwide, frequently diagnosed at advanced stages with poor prognosis, indicating on need for new diagnostic and prognostic markers. The aim of the study was to determine the expression of IL-32, proinflammatory and angiogenic mediators, in patients with diffuse and intestinal gastric cancer and the relationship with clinicopathological aspects.

Material And Methods: The tissue samples of diffuse and intestinal types of tumor of 70 patients with gastric cancer were analyzed.

IL-33 receptor (ST2) deficiency downregulates myeloid precursors, inflammatory NK and dendritic cells in early phase of sepsis.

Background: Sepsis is a life-threatening disease mediated by profound disturbances in systemic inflammatory response to infection. IL-33 is multifunctional regulator of numerous aspects of innate and adaptive immune response. The aim of this article was to further evaluate the role of IL-33 receptor (ST2) in different pathways of innate immunity during early polymicrobial sepsis.

The organic ester -diethyl-()-ethylenediamine--di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis.

Pharmacological treatment of cancer is mostly limited by drug-toxicity and resistance. It has been noticed that new organic ester ligand, diethyl-()-ethylenediamine--di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE-EDCP) showed effective cytotoxic capacities against several human and mouse cancer cell lines. However, its effects on tumor growth and metastasis are unexplored.

Attenuation of NK cells facilitates mammary tumor growth in streptozotocin-induced diabetes in mice.

Diabetic patients have higher incidence and mortality of cancer. Recent study revealed that hyperglycemia-induced oxidative stress is involved in the acceleration of tumor metastasis. We used model of high-dose streptozotocin-induced diabetes to investigate its effect on tumor growth and modulation of antitumor immune response of 4T1 murine breast cancer in BALB/c mice.

The Potential of Frog Skin-Derived Peptides for Development into Therapeutically-Valuable Immunomodulatory Agents.

The aim of this article is to review the immunoregulatory actions of frog skin-derived peptides in order to assess their potential as candidates for immunomodulatory or anti-inflammatory therapy. Frog skin peptides with demonstrable immunomodulatory properties have been isolated from skin secretions of a range of species belonging to the families Alytidae, Ascaphidae, Discoglossidae, Leptodactylidae, Pipidae and Ranidae. Their effects upon production of inflammatory and immunoregulatory cytokines by target cells have been evaluated ex vivo and effects upon cytokine expression and immune cell activity have been studied in vivo by flow cytometry after injection into mice.

Interleukin-6 in Schizophrenia-Is There a Therapeutic Relevance?

Renewing interest in immune aspects of schizophrenia and new findings about the brain-fat axis encourage us to discuss the possible role of interleukin-6 (IL-6) in schizophrenia. Previously, it was suggested that a primary alteration of the innate immune system may be relevant in schizophrenia. Functional dichotomy of IL-6 suggests that this chemical messenger may be responsible for regulating the balance between pro- and anti-inflammatory responses, with tissue-specific properties at the periphery and in the central nervous system.

The frog skin host-defense peptide frenatin 2.1S enhances recruitment, activation and tumoricidal capacity of NK cells.

Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen.

Angiogenic and lymphangiogenic profiles in histological variants of papillary thyroid carcinoma.

Introduction: Papillary thyroid carcinoma (PTC) is a well‑differentiated tumor that occurs in several histological variants whose biological behaviors remain unclear. Angiogenesis and lymphangiogenesis are critical processes that enable tumor progression.

Objectives: The aim of this study was to evaluate the angiogenic and lymphangiogenic phenotypes of PTC, considering the differences between histological variants.

Circulating and tissue galectin-1 and galectin-3 in colorectal carcinoma: association with clinicopathological parameters, serum CEA, IL-17 and IL23.

Purpose: Galectins are modulators of many processes critical for tumor progression and metastasis but their clinical significance is still unclear. The objective of this study was to analyze the clinical significance of Galectin-1 and Galectin-3 in the tissue and sera of patients with colorectal carcinoma (CRC). Examined were also their association with serum CEA, IL-17 and IL-23 in CRC patients.

Galectin-3 Ablation Enhances Liver Steatosis, but Attenuates Inflammation and IL-33-Dependent Fibrosis in Obesogenic Mouse Model of Nonalcoholic Steatohepatitis.

The importance of Galectin-3 (Gal-3) in obesity-associated liver pathology is incompletely defined. To dissect the role of Gal-3 in fibrotic nonalcoholic steatohepatitis (NASH), Gal-3-deficient (LGALS3(-/-)) and wild-type (LGALS3(+/+)) C57Bl/6 mice were placed on an obesogenic high fat diet (HFD, 60% kcal fat) or standard chow diet for 12 and 24 wks. Compared to WT mice, HFD-fed LGALS3(-/-) mice developed, in addition to increased visceral adiposity and diabetes, marked liver steatosis, which was accompanied with higher expression of hepatic PPAR-γ, Cd36, Abca-1 and FAS.

In vivo administration of the frog skin peptide frenatin 2.1S induces immunostimulatory phenotypes of mouse mononuclear cells.

Host-defense peptides secreted by epithelial cells exhibit cytotoxic and immunoregulatory effects in order to protect the organism against invading microorganisms. Antimicrobial peptides derived from frog skin display both immunostimulatory and immunosuppressive actions as demonstrated by in vitro cytokine production by macrophages. Frenatin 2.

Anti-cancer, immunoregulatory, and antimicrobial activities of the frog skin host-defense peptides pseudhymenochirin-1Pb and pseudhymenochirin-2Pa.

Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog Pseudhymenochirus merlini (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC50<12 μM) against non-small cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells but are also hemolytic against human erythrocytes (LC50=28±2 μM for Ps-1Pb and LC50=6±1 μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC50 against non-neoplastic human umbilical vein (HUVEC) cells=68±2 μM).

Effects of tigerinin peptides on cytokine production by mouse peritoneal macrophages and spleen cells and by human peripheral blood mononuclear cells.

The tigerinins are a family of cationic, cyclic peptides of unknown biological function produced in the skins of diverse frog species. Tigerinin-1R (RVCSAIPLPICH.NH2) from Hoplobatrachus rugulosus (Dicroglossidae), tigerinin-1V (RICYAMWIPYPC) from Lithobates vaillanti (Ranidae), and tigerinin-1M (WCPPMIPLCSRF.

Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells.

The role of IL-33/ST2 pathway in antitumor immunity is unclear. Using 4T1 breast cancer model we demonstrate time-dependent increase of endogenous IL-33 at both the mRNA and protein levels in primary tumors and metastatic lungs during cancer progression. Administration of IL-33 accelerated tumor growth and development of lung and liver metastases, which was associated with increased intratumoral accumulation of CD11b(+) Gr-1(+) TGF-β1(+) myeloid-derived suppressor cells (MDSCs) that expressed IL-13α1R, IL-13-producing Lin(-) Sca-1(+) ST2(+) innate lymphoid cells (ILCs) and CD4(+) Foxp3(+) ST2(+) IL-10(+) Tregs compared to untreated mice.