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Three unusual amino-phloroglucinols, named helichrytalicines A-C, along with seventeen known compounds including acetophenones, tremetrone derivatives, low-molecular weight phenols, flavonol glucosides, have been isolated from the medium-polar extract of Helichrysum italicum (Roth) G. Don, a medicinal plant typical of the Mediterranean vegetation. The structures of the compounds have been elucidated based on extensive 2D-NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and HSQC-TOCSY, along with Q-TOF HRMS 2 analysis. Stereostructure of the new compounds has been elucidated by Mosher's method and NOESY experiment. Antimicrobial properties against Staphylococcus epidermidis of selected compounds have been evaluated. [ABSTRACT FROM AUTHOR]

The phytochemical study of Bellis sylvestris has been carried out. This study led to the isolation of 28 secondary metabolites belonging to different classes. The structures of these compounds have been elucidated on the basis of extensive 2D-NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and HSQC-TOCSY, along with Q-TOF HRMS 2 analysis. Three of them, two megastimane derivatives and a glycoside of 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone, were reported for the first time. The compounds isolated from Bellis sylvestris were tested for their antimicrobial activity against some microorganisms associated with urinary tract infections ( Proteus mirabilis , Pseudomonas aeruginosa , Streptococcus aureus and Candida albicans ). The bacterial strains showed variable degrees of susceptibility to the compounds. Selected compounds were evaluated for their anti-biofilm properties against Pseudomonas aeruginosa and Candida albicans . Caffeic and rosmarinic acids were the once showing a higher reduction rate of biofilm formation. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis , a human pathogen, is a Gram-negative bacillus and a compulsory intracellular parasite. It is the most common cause of bacterial sexually transmitted infections in both industrialized and developing countries. In women, untreated genital infections can result in devastating consequences such as pelvic inflammatory disease, ectopic pregnancy, and even infertility. Lactobacillus crispatus is an important urogenital species that is routinely found in the vagina of healthy women. Lactobacilli are involved in the maintenance of the normal vaginal microbiota and their dominance in the vagina suggests that they play a crucial role in protecting the genitourinary tract against pathological conditions. Lactobacilli can act through the activation of the immune system, but C. trachomatis is able to effectively evade immune surveillance in some individuals. The aim of our study was to investigate the immunomodulatory efficacy of the potential probiotic strain L. crispatus in HeLa and J774 cells subjected to C. trachomatis infection by studying the expression of the inflammatory cytokines IL-6, IL-8, TNF-α and IL-10. Our results demonstrated, firstly, the lack of any cytotoxic effect on the epithelial cells and macrophages when treated with L. crispatus and its supernatant; in addition, L. crispatus and its supernatant inhibited C. trachomatis adhesion and infectivity in human epithelial cells and macrophages. Our study then showed that L. crispatus and its supernatant reduced IL-6, IL-8 and TNF-α production in C. trachomatis -infected HeLa and J774 cells. In contrast, a significant upregulation of the IL-10 expression in HeLa and J774 cells by L. crispatus and supernatant was also demonstrated. Our data indicate that L. crispatus specifically enhances the production of the IL-10 anti-inflammatory cytokine in contrast to the inhibitory effect of L. crispatus on the pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Lymphedematous areas are sites of regional immune destabilization depicting a typical example of an immunocompromised cutaneous district (ICD). This study evaluates the expression of some components of the skin innate immunity on lymphedematous limbs with the aim to clarify some facets of the ICD. Patients selected underwent two skin biopsies: One was obtained from the limb affected by lymphedema, another from the contralateral healthy limb. Expression of some components of the skin innate immunity was analyzed by reverse transcription-polymerase chain reaction. Stronger gene expression of Toll-like receptor 2 (TLR-2), human β-defensin 2 (HBD-2), desmoglein 1, desmoglein 3, matrix metallopeptidase 9 (MMP-9), and interleukin 10 (IL-10) was found in keratinocytes derived from the affected limb compared with that of keratinocytes derived from contralateral healthy limb. Downregulation of survivin and vasoactive intestinal polypeptide (VIP) gene expression was found in the affected limbs. No induction of IL-1α and tumor necrosis factor α (TNF-α) was detectable in keratinocyte cultures obtained from both lymphedematous and normal limbs. Different phases and components of skin innate immunity turned out to be altered in the lymphedematous sites. Molecular alterations were similar in all patients recruited in the study. These changes might favor the local appearance or progression of opportunistic diseases such as tumors, infections, and immune-mediated skin disorders. [ABSTRACT FROM AUTHOR]

Abstract: Two new acylated styrylpyrones, one 5-methoxy-1(3H)-isobenzofuranone glucoside and a hydroxymethyl-orcinol derivative, along with sixteen known aromatic metabolites, including lignans, quinic acid derivatives low-molecular weight phenol glucosides, have been isolated from the methanol extract of Helichrysum italicum, a medicinal plant typical of the Mediterranean vegetation. The structures of these compounds have been elucidated on the basis of extensive 2D-NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and HSQC-TOCSY, along with Q-TOF HRMS2 analysis. Selected compounds were evaluated for their anti-biofilm properties against Pseudomonas aeruginosa. [Copyright &y& Elsevier]

Abstract: The most important function of the skin is the formation of a barrier between the “inside” and the “outside” of the organism, which prevents invasion of pathogens and fends off chemical assaults as well as the unregulated loss of water and solutes. The physical barrier is mainly localized in the stratum corneum, which consists of protein-enriched cells and lipid-enriched intercellular domains. Any modifications in epidermal differentiation and lipid composition results in altered barrier function, a central event in various skin alterations and diseases. This contribution presents a brief description of the structure of the skin, paying attention to the most important components responsible for skin barrier function. [Copyright &y& Elsevier]

Helicobacter pylori colonizes the human stomach and causes gastric disease. The resulting gastric damage is a multi-step process involving several molecular factors and different target cells. Th1 cytokines released by neutrophils and lymphoid cells that infiltrate gastric mucosa, nitric oxide production and inducible nitric oxide synthase (iNOS) are associated with immune activation and tissue injury. Many other molecular processes such as apoptosis, as well as angiogenic factors and integrins, are involved in H. pylori pathogenesis. We used cancer gastric cells AGS and MKN as experimental models to evaluate apoptotic rates, iNOS gene expression with and without the presence of interferon-γ (IFN-γ), placenta growth factor gene expression and αv modulation. Our results show that AGS cells stimulated with H. pylori underwent apoptosis. Moreover, the addition of IFN-γ caused a further increase in iNOS gene expression and in the apoptotic rates. We also found early modulation in PlGF and αv expression, and noted that p53 and bax gene expression was involved in the apoptotic process. Taken together, these findings demonstrate that H. pylori employs a series of mechanisms to avoid the host defense and cause gastric mucosa damage. One H. pylori pathogenic mechanism for causing gastric damage is the induction of iNOS-dependent apoptosis that is strongly enhanced by IFN-γ. Thus, data obtained indicate that Th1 cytokines such as IFN-γ, via modulation of iNOS gene expression, may contribute to an increase in the pathogenicity of H. pylori infections. [Copyright &y& Elsevier]

Herein we report the preparation of 3,4-dibenzylfurans and some oxidized derivatives with lignan backbone. The compounds were prepared using the Friedel-Crafts reaction with BF 3 etherate as catalyst, demethylation with iodocyclohexane, acetylation and oxidation reactions. The antimicrobial activity was evaluated through their capacity to inhibit the growth of Gram positive and Gram negative bacteria, and of the yeast Candida albicans. Among ten products assayed four furans displayed a good antimicrobial activity against Staphylococcus aureus , S. epidermidis and C. albicans ; on the contrary, none of the compounds were active against Pseudomonas aeruginosa. One of them inhibited the growth of S. aureus , S. epidermidis (biofilm producer strain) and C. albicans at 16 μg/mL, showing a bactericidal activity already after one hour of treatment. In summary, the results suggest a possible use of these derivatives for general disinfection practices or antimicrobial agents in cosmesis skin-care. [ABSTRACT FROM AUTHOR]

Abstract: Human β-defensin 2 is an antimicrobial peptide that is produced by several epithelial cells after stimulation with micro-organisms and inflammatory mediators. Gram-negative bacteria, which are typically detected in periodontal pockets in periodontitis, elicit a stronger antibacterial peptide response of human β-defensin 2 by epithelial cells. In this study, we investigated whether Chlamydia pneumoniae is able both to enter and grow in human gingival fibroblasts (HGF), to modify the production of cytokines, and is involved in regulation of β-defensin 2 expression. Gingival fibroblasts discarded from periodontal procedures on healthy young individuals were infected with viable C. pneumoniae or with heat- or ultraviolet-inactivated organisms at a multiplicity of infection of 4 inclusion-forming units per cell. Our results demonstrate that after 48 h of incubation with viable C. pneumoniae, gingival fibroblasts showed a proliferative response as seen by both colorimetric assay and direct cell count (40% and 45%, respectively). Moreover, cells incubated with viable or ultraviolet light-inactivated C. pneumoniae organisms showed an increase in the levels of interleukin-6, interleukin-10 and human β-defensin 2 in a time-dependent fashion, while the cells infected with heat-killed bacteria did not show a significant production either of the cytokines or β-defensin 2 at any time. In conclusion, we demonstrate the correlation between multiplication of C. pneumoniae in human gingival fibroblasts and release of interleukin-6, interleukin-10 and up-regulation of β-defensin 2, suggesting that gingival fibroblasts may be a periodontium niche for obligate intracellular C. pneumoniae and may play a role in innate gingival immune system and inflammatory response mechanisms of periodontitis. [Copyright &y& Elsevier]

Abstract: Epithelia in the human airways, from the nasal aperture to the alveoli, are covered in a protective film of fluid containing a number of antimicrobial proteins. Defensins are single-chain, strongly cationic peptides and are one of the most extensively studied classes of antimicrobial peptides. Moxifloxacin (MXF) is a fluoroquinolone that acts against both Gram positive and Gram negative bacteria. In this study, we evaluated the effects of HBD2, MXF and the association MXF/HBD2 on some cytokines and on the ICAM-1 expression in LPS-stimulated A549 cells. Our results suggest that by lowering the epithelial cell-derived IL-1β, IL-6, IL-8 and ICAM-1 expression, the MXF/HBD2 association interferes with the multifunctional cytokine network evolving during inflammatory processes of the respiratory tract; this anti-inflammatory potential could be of great value in the treatment of inflammatory disorders. [Copyright &y& Elsevier]

The occurrence of increased antibiotic resistance has reduced the availability of drugs effective in the control of infectious diseases, especially those caused by various combinations of bacteria and/or fungi that are often associated with poorer patient outcomes. In the hunt for novel antibiotics of interest to treat polymicrobial diseases, molecules bearing guanidine moieties have recently come to the fore in designing and optimizing antimicrobial agents. Due to their remarkable antibacterial and antifungal activities, labdane diterpenes are also attracting increasing interest in antimicrobial drug discovery. In this study, six different guanidines prenylated with labdanic fragments were synthesized and evaluated for their antimicrobial properties. Assays were carried out against both non-resistant and antibiotic-resistant bacteria strains, while their possible antifungal activities have been tested on the yeast Candida albicans. Two of the synthesized compounds, namely labdan-8,13(R)-epoxy-15-oyl guanidine and labdan-8,13(S)-epoxy-15-oyl guanidine, were finally selected as the best candidates for further developments in drug discovery, due to their antimicrobial effects on both Gram-negative and Gram-positive bacterial strains, their fungicide action, and their moderate toxicity in vivo on zebrafish embryos. The study also provides insights into the structure-activity relationships of the guanidine-functionalized labdane-type diterpenoids. [Display omitted] • Synthesis of acyl guanidines prenylated with labdanic diterpenoids. • Acylguanidines with a broad-spectrum antimicrobial activity. • Synergistic action of acylguanidines in combination with known antibiotics. • A short synthesis of natural ent -gomeric acids via a tandem HWE-oxa Michael reactions. [ABSTRACT FROM AUTHOR]