A prospective randomized study on limits of colposcopy and histology: the skill of colposcopist and colposcopy-guided biopsy in diagnosis of cervical intraepithelial lesions.

Background: The main objective of our study was to evaluate the colposcopist ability to correctly identify the worst area of a cervical lesion where biopsy should be performed; the secondary objective was to investigate the influence of the colposcopist skill in grading cervical preneoplastic lesions.

Methods: 296 patients referred for colposcopy were enrolled in a prospective study. All patients were randomized in two groups: in the first group, "senior group", the colposcopy was performed by an experienced colposcopist; in the second group, "junior group", the colposcopy was performed by a less experienced colposcopist.

Can Small Chemical Modifications of Natural Pan-inhibitors Modulate the Biological Selectivity? The Case of Curcumin Prenylated Derivatives Acting as HDAC or mPGES-1 Inhibitors.

Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C5 (isopentenyl, 5-8), C10 (geranyl, 9-12), and C15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E2 synthase-1 (mPGES-1).

L-ergothioneine supplementation during culture improves quality of bovine in vitro-produced embryos.

The aim of this study was to evaluate whether supplementation of bovine culture medium with the natural antioxidant L-ergothioneine (LE), improves in vitro blastocyst development and quality, assessed as resistance to cryopreservation, total cells number, cellular differentiation, and apoptosis index. Abattoir-derived oocytes were matured and fertilized in vitro according to standard procedure. Twenty hours after IVF, presumptive zygotes were cultured in synthetic oviduct fluid with 0, 0.

Comparison of bidirectional barbed suture Stratafix and conventional suture with intracorporeal knots in laparoscopic myomectomy by office transvaginal hydrolaparoscopic follow-up: a preliminary report.

Objectives: To compare surgical outcomes of different types of intracorporeal sutures for laparoscopic posterior myomectomy, by a prospective randomized study.

Study Design: Prospective randomized study on 47 patients with single posterior intramural myoma (4-7cm in diameter) undergoing laparoscopic myomectomy. The patients enrolled were divided into two groups, one operated using conventional suture in double strand, and the other with bidirectional barbed suture Stratafix.

Endometrioma size is a relevant factor in selection of the most appropriate surgical technique: a prospective randomized preliminary study.

Objectives: To assess and compare the ovarian reserve in patients with different-sized endometriomas undergoing cystectomy or ablative surgery in order to determine the best surgical approach to safeguard healthy ovarian tissue.

Study Design: Prospective randomized study on 48 patients with unilateral single ovarian endometriomas. Patients were allocated into two groups based on endometrioma size: <5cm (n=26, Group A, small endometriomas) and ≥5cm (n=22, Group B, large endometriomas).

Effect of pour-on alphacypermethrin on feed intake, body condition score, milk yield, pregnancy rates, and calving-to-conception interval in buffaloes.

The aims of this study were to assess the efficacy of alphacypermethrin (ACYP) on pediculosis due to Haematopinus tuberculatus and to evaluate the influence of the treatment on productive and reproductive performance in buffaloes (Bubalus bubalis) reared in an intensive system. The trial was performed on 56 pluriparous buffaloes at 86.8 ± 8.

In-office transvaginal hydrolaparoscopy: a step-by-step, intraoperative pain evaluation.

Purpose: Transvaginal hydrolaparoscopy (THL) is a mini-invasive technique, which allows exploration of the posterior pelvis. THL can be carried out as an office procedure and may replace hysterosalpingography and laparoscopy for the diagnosis of infertility. The aim of this study was to assess pain level during each step of THL.

Identification and mechanism of action analysis of the new PARP-1 inhibitor 2″-hydroxygenkwanol A.

Background: Poly(ADP-ribose) polymerase 1 (PARP-1) activity has been implicated in the pathogenesis of numerous diseases as cancer, inflammation, diabetes and neurodegenerative disorders, therefore the research for new PARP-1 inhibitors is still an active area.

Methods: To identify new potential PARP-1 inhibitors, we performed a screening of a small-molecule library consisting of polyphenols isolated from plants used in the traditional medicine, by Surface Plasmon Resonance (SPR). Biochemical and cellular assays were performed to confirm SPR results and select the promising candidate(s).

9H-purine scaffold reveals induced-fit pocket plasticity of the BRD9 bromodomain.

The 2-amine-9H-purine scaffold was identified as a weak bromodomain template and was developed via iterative structure based design into a potent nanomolar ligand for the bromodomain of human BRD9 with small residual micromolar affinity toward the bromodomain of BRD4. Binding of the lead compound 11 to the bromodomain of BRD9 results in an unprecedented rearrangement of residues forming the acetyllysine recognition site, affecting plasticity of the protein in an induced-fit pocket. The compound does not exhibit any cytotoxic effect in HEK293 cells and displaces the BRD9 bromodomain from chromatin in bioluminescence proximity assays without affecting the BRD4/histone complex.

Structural Insights for the Optimization of Dihydropyrimidin-2(1H)-one Based mPGES-1 Inhibitors.

The recently crystallized structure of microsomal prostaglandin E2 synthase 1 (mPGES-1) in complex with the inhibitor LVJ (PDB code: 4BPM) offered new structural information for the optimization of the previously identified lead compound 1 (IC50 = 4.16 ± 0.47 μM), which contains the privileged dihydropyrimidin-2-one chemical core.

Molecular decodification of gymnemic acids from Gymnema sylvestre. Discovery of a new class of liver X receptor antagonists.

The individual chemical components of commercial extract of Gymnema sylvestre, a medicinal plant used in the traditional systems of the Indian medicine for its antidiabetic and hypolipidemic properties, were isolated and evaluated for their capability to act as modulators of nuclear and membrane receptors involved in glucose and lipid homeostasis. The study disclosed for the first time that individual gymnemic acids are potent and selective antagonists for the β isoform of LXR. Indeed the above activity was shared by the most abundant aglycone gymnemagenin (10) whereas gymnestrogenin (11) was endowed with a dual LXRα/β antagonistic profile.

Targeting the Hsp90 C-terminal domain by the chemically accessible dihydropyrimidinone scaffold.

Hsp90 C-terminal ligands are potential new anti-cancer drugs alternative to the more studied N-terminal inhibitors. Here we report the identification of a new dihydropyrimidinone binding the C-terminus, which is not structurally related to other well-known natural and nature-inspired inhibitors of this second druggable Hsp90 site.

Molecular mechanism of tanshinone IIA and cryptotanshinone in platelet anti-aggregating effects: an integrated study of pharmacology and computational analysis.

Tanshinone IIA and cryptotanshinone are two pharmacologically active diterpenoids extracted from the roots of Salvia milthiorriza Bunge, a plant used in Chinese traditional medicine for the treatment of some cardiovascular and cerebrovascular disease. Until now, the molecular mechanisms of action of these two diterpenoids on platelets are partially known. To clarify this aspect, here we utilized an integrated study of pharmacology and computational analysis.

Effect of resveratrol supplementation during culture on the quality and cryotolerance of bovine in vitro produced embryos.

The aim of the study was to evaluate whether resveratrol supplementation of bovine culture medium improves in vitro blastocyst development, embryo cryotolerance and cell numbers. Abattoir-derived oocytes were matured and fertilized in vitro according to standard procedure. Twenty hours after IVF, zygotes were cultured in SOF medium, supplemented with 0 (control, n=439), 0.

Structural evidence of N6-isopentenyladenosine as a new ligand of farnesyl pyrophosphate synthase.

N6-isopentenyladenosine (i6A), a modified nucleoside belonging to the cytokinin family, has shown in humans many biological actions, including antitumoral effects through the modulation of the farnesyl pyrophosphate synthase (FPPS) activity. To investigate the relationship between i6A and FPPS, we undertook an inverse virtual screening computational target searching, testing i6A on a large panel of 3D protein structures involved in cancer processes. Experimentally, we performed an NMR investigation of i6A in the presence of FPPS protein.

Hyalachelins A-C, unusual siderophores isolated from the terrestrial myxobacterium Hyalangium minutum.

Three new siderophores, termed hyalachelins A-C (1-3), were isolated from the terrestrial myxobacterium Hyalangium minutum. Their structures were determined by 2D NMR and HR-MS/MS experiments, and their stereochemical configuration was established by a combination of NMR data, quantum mechanical calculations, and circular dichroism experiments. Hyalachelins are unusual catecholate-type siderophores that bear a 3,7,8-trihydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

Synthetic cyanoacrylic glue in the prevention of post-operative lymphocele after pelvic lymphadenectomy in patients with uterine malignancies: A prospective, single-blind, preliminary study.

Objectives: Lymphoceles are among the most common post-operative complications of pelvic lymphadenectomy, with a reported incidence of 1% to 29% in gynecology oncology. Several studies evaluated the effectiveness of biological glues on reducing lymphoceles, but no data on gynecological patients are available. We evaluated the effectiveness of cyanoacrylic glues (n-butyl cyanoacrylate) (Glubran 2 - GEM s.

Pharmacological evaluation and docking studies of α,β-unsaturated carbonyl based synthetic compounds as inhibitors of secretory phospholipase A₂, cyclooxygenases, lipoxygenase and proinflammatory cytokines.

Arachidonic acid and its metabolites have generated high level of interest among researchers due to their vital role in inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as synergistic anti-inflammatory effect. A series of novel α,β-unsaturated carbonyl based compounds were synthesized and evaluated for their inhibitory activity on secretory phospholipase A₂ (sPLA₂), cyclooxygenases (COX), soybean lipoxygenase (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-α.

Exploration of the dihydropyrimidine scaffold for the development of new potential anti-inflammatory agents blocking prostaglandin E₂ synthase-1 enzyme (mPGES-1).

Agents targeting microsomal prostaglandin E2 synthase-1 (mPGES-1) would inhibit only PGE2 production induced by inflammatory stimuli and thus could represent a valuable alternative to non-steroidal anti-inflammatory drugs (NSAIDs) as they should be free from the severe side effects of the classic anti-inflammatory drugs. Although several mPGES-1 inhibitors have been so far identified, none of them is currently in clinical trials, therefore the discovery of new molecular platforms, able to interfere with this interesting target, is urgently required. Here, we report the results of a focused collection of dyhidropyrimidin-2(1H)-one based molecules projected by Virtual Screening computational techniques.

New steroids with a rearranged skeleton as (h)P300 inhibitors from the sponge Theonella swinhoei.

Swinhoeisterols A (1) and B (2), two novel sterols with an unprecedented 6/6/5/7 ring system, were isolated from the sponge Theonella swinhoei. The structures and absolute configurations were elucidated by spectroscopic analysis, X-ray single-crystal diffraction, modified Mosher's method, and TDDFT/ECD calculations. The cytotoxicity of these compounds toward A549 and MG-63 cells encourages studies on their potential target using an inverse virtual screening approach.

Bio-inspired benzo[k,l]xanthene lignans: synthesis, DNA-interaction and antiproliferative properties.

In this work twelve benzo[k,l]xanthene lignans were synthesized by biomimetic, Mn-mediated oxidative coupling of caffeic esters and amides. These compounds, bearing different flexible pendants at position C1/C2 of the aromatic core, interact with DNA in a dual mode, as confirmed by DF-STD NMR analysis and molecular docking: the planar core acts as a base pair intercalant, whereas the flexible pendants act as minor groove binders. Their antiproliferative activity was evaluated on a panel of six tumor cell lines: HT-29, Caco-2, HCT-116 (human colon carcinoma), H226, A549 (human lung carcinoma), and SH-SY5Y (human neuroblastoma).

GRP78 mediates cell growth and invasiveness in endometrial cancer.

Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Very recently we reported for the first time that GRP78 is increased in endometrial tumors. However, whether GRP78 could play a role in the growth and/or invasiveness of endometrial cancer cells is still unknown.

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of (13)C chemical shifts.

In this paper the stereostructural investigation of two new oxygenated polyketides, plakilactones G and H, isolated from the marine sponge Plakinastrella mamillaris collected at Fiji Islands, is reported. The stereostructural studies began on plakilactone H by applying an integrated approach of the NOE-based protocol and quantum mechanical calculations of (13)C chemical shifts. In particular, plakilactone H was used as a template to extend the application of NMR-derived interproton distances to a highly flexible molecular system with simultaneous assignment of four non-contiguous stereocenters.

Direct interaction of garcinol and related polyisoprenylated benzophenones of Garcinia cambogia fruits with the transcription factor STAT-1 as a likely mechanism of their inhibitory effect on cytokine signaling pathways.

Garcinol (1), a polyisoprenylated benzophenone occurring in Garcinia species, has been reported to exert anti-inflammatory activity in LPS-stimulated macrophages, through inhibition of NF-κB and/or JAK/STAT-1 activation. In order to provide deeper insight into its effects on the cytokine signaling pathway and to clarify the underlying molecular mechanisms, 1 was isolated from the fruits of Garcinia cambogia along with two other polyisoprenylated benzophenones, guttiferones K (2) and guttiferone M (3), differing from each other in their isoprenyl moieties and their positions on the benzophenone core. The affinities of 1-3 for the STAT-1 protein have been evaluated by surface plasmon resonance and molecular docking studies and resulted in KD values in the micromolar range.