Molecular dynamics simulations have been used to investigate the confinement packing characteristics of small hydrophilic （N-acetyl-glycine-methylamide, Nagma） and hydrophobic ...（N-acetyl-leucine-methylamide, Nalma） biomolecules in large diameter single-wall carbon nanotubes （SWCNTs）. We find that hydrophilic biomolecules easily fill the nanotube and self organize into a geometrical configuration which reminds the water structural organization under SWCNT confinement. The packing of hydrophilic biomolecules inside the cylinder confines all water molecules in its core, which enhances their mobility. Conversely, hydrophobic biomolecules accommodate into the nanotubes with a trend for homogeneous filling, which generate unstable small pockets of water and drive toward a state of dehydration. These results shed light on key parameters important for the encapsulation of biomolecules with direct relevance for long-term storage and prevention of degradation.
Bacterial surface molecules are crucial for the establishment of a successful rhizobia-legume symbiosis, and, in most bacteria, are also critical for adherence properties, surface colonization, and ...as a barrier for defense. Rhizobial mutants defective in the production of exopolysaccharides (EPSs), lipopolysaccharides (LPSs), or capsular polysaccharides are usually affected in symbiosis with their plant hosts. In the present study, we evaluated the role of the combined effects of LPS and EPS II in cell-to-cell and cell-to-surface interactions in Sinorhizobium meliloti by studying planktonic cell autoaggregation, biofilm formation, and symbiosis with the host plant Medicago sativa. The lpsB mutant, which has a defective core portion of LPS, exhibited a reduction in biofilm formation on abiotic surfaces as well as altered biofilm architecture compared with the wild-type Rm8530 strain. Atomic force microscopy and confocal laser microscopy revealed an increase in polar cell-to-cell interactions in the lpsB mutant, which might account for the biofilm deficiency. However, a certain level of biofilm development was observed in the lpsB strain compared with the EPS II-defective mutant strains. Autoaggregation experiments carried out with LPS and EPS mutant strains showed that both polysaccharides have an impact on the cell-to-cell adhesive interactions of planktonic bacteria. Although the lpsB mutation and the loss of EPS II production strongly stimulated early attachment to alfalfa roots, the number of nodules induced in M. sativa was not increased. Taken together, this work demonstrates that S. meliloti interactions with biotic and abiotic surfaces depend on the interplay between LPS and EPS II.
Uveal melanoma, in spite of its rarity, represents the most common primitive intraocular malignant neoplasm of the adults; it affects choroid, ciliary bodied and iris and remains clinically silent ...for a long time, being accidentally discovered by routine ophthalmic exams. Prognosis of uveal melanoma is poor and frequently characterized by liver metastases, within 10-15 years from diagnosis. Autophagy is a multi-step catabolic process by which cells remove damaged organelles and proteins and recycle nutrients. It has been hypothesized that in early stages of tumorigenesis autophagy has a tumor suppressor role while, in more advanced stages, it may represent a survival mechanism of neoplastic cells in response to stress. Several proteins related to autophagy cascade have been investigated in numerous subtypes of human cancer, with overall controversal results. In this paper we studied the immunohistochemical expression of 3 autophagy related proteins (Beclin-1, p62 and ATG7) in a cohort of 85 primary uveal melanoma treated by primary enucleation (39 with metastasis and 46 non metastatic) and correlated their expression with clinico-pathological parameters and blood vascular microvessel density, in order to investigate the potential prognostic role of autophagy in this rare neoplasm. We found that high immunohistochemical levels of Beclin-1 correlated with a lower risk of metastasis and higher disease-free survival times, indicating a positive prognostic role for Beclin-1 in uveal melanoma. No statistically significative differences regarding the expression of ATG7 and p62 between metastatic and non metastatic patients was detected.
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•Protein-polymer conjugation with biodegradable polymers.•Multiple technique approach for the protein conjugate’s characterization.•Proteins still folded and active in physiological ...conditions after bioconjugation.•Trend between the properties of the conjugates and the polymer molar mass.
Protein-polymer conjugates are used to treat several diseases. PEGylation, i.e. the modification with poly(ethylene glycol) (PEG) is the currently used strategy. However, due to its non-biodegradability, the design of effective and degradable conjugates is of both academic and industry potential. We present the preparation and studies of the activity and stability of novel biodegradable myoglobin-polyphosphoester conjugates. Poly(ethyl ethylene phosphate) (PEEP) is a water-soluble polyphosphoester, which had been reported to be biocompatible and biodegradable. PEEP is a promising candidate as a degradable substitute for the “gold standard” PEG, which can cause long-term effects, as it is not degradable. PEEPylated conjugates with a variable degree of polymer grafting were synthesized, characterized (with online triple detection size exclusion chromatography, mass spectrometry, and gel electrophoresis), and compared with PEGylated analogs. We highlight differences in how the structure, the number, and the length of the polymer influence the properties of the conjugates. Overall, the analyses conducted (including activity assay, calorimetry, and fluorimetry measurements) show that the covalent attachment of the polymer does not irrevocably affect the protein’s features under physiological conditions, suggesting the potential of this new class of polymers for the design of a new generation of fully degradable conjugates.
Aberrant p53 immunohistochemical expression is used to identify the copy-number-high/TP53-mutant subgroup of endometrial cancer (EC). We aimed to determine the diagnostic accuracy of p53 ...immunohistochemistry as surrogate for TP53 sequencing through a systematic review and meta-analysis.
Electronic databases were searched from their inception to June 2019. All studies assessing p53 expression and TP53 mutations in EC were included. Diagnostic accuracy was assessed based on area under the curve (AUC). Immunohistochemical criteria used to define aberrant p53 expression were “overexpression” and “overexpression or complete absence”. Subgroup analysis was based on the sequencing technique adopted (Polymerase Chain Reaction + sequencing, or next generation sequencing, NGS).
Thirteen observational studies with 727 endometrial cancers were included. Both “overexpression” and “overexpression or complete absence” showed high diagnostic accuracy (AUC = 0.9088 and 0.9030, respectively). The subgroup with “overexpression” and NGS showed the best results, with very high diagnostic accuracy (AUC = 0.9927).
In conclusion, immunohistochemistry for p53 is a highly accurate surrogate of TP53 sequencing. Overexpression of p53 in ≥70−80% showed the best accuracy in predicting TP53 mutations. Further studies in this field should adopt optimized immunohistochemical procedures and take into account less common p53 patterns (e.g. cytoplasmic expression).
Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have ...investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased β‐catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth‐related factors.
Malus pumila Mill. cv Annurca extract was tested on hair follicle dermal papilla cells, demonstrating its ability to reduce intracellular reactive oxygen species and to induce the expression of hair growth‐related factors. AT HAIR‐FUL AA® may be a potential therapeutically useful natural substance for preventing or treating hair loss.
L. Greuter belonging to the Asteraceae family, is an aromatic herbaceous plant native to the Mediterranean region. This plant species has been extensively studied for its biological activities, ...including antioxidant, antitumor, antimicrobial, antifungal, anti-inflammatory, anticholinesterase, and antityrosinase, and for its peculiar metabolic profile. In particular, bioactivities are related to terpenes and flavonoids metabolites, such as borneol (
), tomentosin (
), inuviscolide (
). However,
is also well known for causing health problems both in animals and humans. Moreover, the species is currently undergoing a dramatic northward expansion of its native range related to climate change, now including North Europe, California, and Australia. This review represents an updated overview of the 52 literature papers published in Scopus and PubMed dealing with expansion, chemistry (262 different compounds), pharmacological effects, and toxicology of
up to October 2021. The review is intended to boost further studies to determine the molecular pathways involved in the observed activities, bioavailability, and clinical studies to explore new potential applications.
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