How could nanobiotechnology improve treatment outcomes of anti-TNF-α therapy in infammatory bowel disease? Current knowledge, future directions

Despite significant advances in therapeutic possibilities for the treatment of inflammatory bowel disease (IBD) in recent years, there is still a big room for improvement. In particular, biological treatment can induce not only clinical remission but also mucosal healing of the gastrointestinal tract. Among these therapeutic molecules, anti-tumor necrosis factor-alpha (anti-TNF-$\alpha$) antibodies were the first to revolutionize treatment algorithms in IBD. However, due to the parenteral route of administration and systemic mode of action, TNF-$\alpha$ blockers are characterised by high rates of immunogenicity-related loss of response and serious adverse events. Moreover, intravenous or subcutaneous therapy is not considered patient-friendly and requires occasional, direct contact with healthcare centres. To overcome these limitations, several attempts have been made to design oral pharmaceutical formulations of these molecules. It is hypothesized that oral anti-TNF-$\alpha$ antibodies therapy can directly provide a targeted and potent anti-inflammatory effect in the inflamed gastrointestinal tissues without significant systemic exposure, improving long-term treatment outcomes and safety. In this review, we discuss the current knowledge and future perspectives regarding different approaches made towards entering a new era of oral anti-TNF-$\alpha$ therapy, namely, the tailoring of biocompatible nanoparticles with anti-TNF-$\alpha$ antibodies for site-specific targeting to IBD. In particular, we discuss the latest concepts applying the achievements of nanotechnology-based drug design in this area.Portuguese Science and Technology Foundation (FCT/MCT), European Funds (PRODUCER/COMPETE)—project UIDB/04469/2020 (strategic fund), co-fnanced by FEDER, under the Partnership Agreement PT2020. The study was also supported by the National Science Centre within the MINIATURA 4 for a single research activity (Grant No. 2020/04/X/ST5/00789) and by the START 2021 Program of the Foundation for Polish Science (FNP) granted to Aleksandra Zielińska.info:eu-repo/semantics/publishedVersio

Cancer nanopharmaceuticals: physicochemical characterization and in vitro/in vivo applications

Physicochemical, pharmacokinetic, and biopharmaceutical characterization tools play a key role in the assessment of nanopharmaceuticals potential imaging analysis and for site-specific delivery of anti-cancers to neoplastic cells/tissues. If diagnostic tools and therapeutic approaches are combined in one single nanoparticle, a new platform called nanotheragnostics is generated. Several analytical technologies allow us to characterize nanopharmaceuticals and nanoparticles and their properties so that they can be properly used in cancer therapy. This paper describes the role of multifunctional nanoparticles in cancer diagnosis and treatment, describing how nanotheragnostics can be useful in modern chemotherapy, and finally, the challenges associated with the commercialization of nanoparticles for cancer therapy.This research was funded by The National Centre for Research and Development (Grant Number INNOMED/I/11/NCBR/2014) from the Innovative Economy Operational Programme founds, in the framework of the European Regional Development Fund, by the Institute of Human Genetics, Polish Academy of Sciences by the internal grant for the implementation of a single scientific activity, and by the Portuguese Science and Technology Foundation (FCT/MCT), European Funds (PRODER/COMPETE)-project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Two- and three-dimensional spectrofluorimetric qualitative analysis of selected vegetable oils for biomedical applications

Vegetable oils obtained from different plants are known for their beneficial effects on prophylaxis and supportive treatment of a great deal of inflammatory-mediated conditions. Their wide range of saturated and unsaturated fatty acids, and the presence of other ingredients (e.g., tocopherols, chlorophylls), provide them with anti-inflammatory, antioxidant and anticancer properties, which are worth being exploited. In this study, we have carried out the spectrofluorometric analysis of selected vegetable oils, namely apricot (Prunus armeniaca) kernel oil; blueberry (Vaccinium spp.) seed oil; argan (Argania spinosa) nut oil; kiwi (Actinidia deliciosa) seed oil; grape (Vitis vinifera) seed oil; evening primrose (Oenothera biennis) oil and meadowfoam (Limnanthes alba) seed oil, with the purpose to detect their fluorescent ingredients for further identification and bioactivity comparison. The obtained two- (2D) and three-dimensional (3D) emission spectra offered a complete description of the fluorescent components of the mixture and revealed different features for studied oils.This work was supported by the projects M-ERA-NET/0004/2015 (PAIRED) and strategic funds, UIDB/04469/2020 (CEB), UIDB/04033/2020 (CITAB) and UIDB/00616/2020 (CQ-VR), from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) from national funds, and cofinanced by FEDER, under the Partnership Agreement PT2020. This work was also supported by the Foundation for the Development of Biotechnology and Genetics POLBIOGEN, Jugosłowia ´nska 57, 60–159 Poznan, Poland.info:eu-repo/semantics/publishedVersio

Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.</p> <p>Methods</p> <p>The analysis of microdeletions was conducted using fluorescence <it>in situ </it>hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the <it>HIRA (TUPLE1, DGCR1</it>) region at 22q11 was used for the hybridisation.</p> <p>Results</p> <p>Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated <it>de novo</it>.</p> <p>Conclusions</p> <p>Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted children's parents.</p

Lunasin – a bioactive peptide from triticale (X Triticosecale Wittmack ) seeds, inhibits proliferation of cancer HeLa and SK-OV-3 cells

The presented study demonstrates the influence of lunasin, a bioactive peptide isolated from seeds of winter triticale, on the proliferation of neoplastic cells. In order to conduct investigations, 2S fraction low-molecular-weight albumin proteins were extracted. SDS-PAGE electrophoresis separation of extracts indicated the presence of a 5 kDa peptide in the crude extract, which corresponded to the weight of lunasin. The next stage of protein purification involved ion-exchange column chromatography in an FPLC system on DEAE Sepharose Fast Flow. The separation of biomolecules by means of 2D electrophoresis confirmed that a peptide with an isoelectric point was present in the area, with a pH of about 5.5 and molecular mass of about 5 kDa. The presence of lunasin in the purified samples was confirmed by Western blot. The lunasin peptide affected the proliferation of cervical cancer (HeLa) and ovarian cancer (SK-OV-3) cell lines. The average decrease in the HeLa cell proliferation rate was 17%. The SK-OV-3 cell line was more susceptible to inhibition by the protein fraction containing lunasin than HeLa cells, with an average decrease in the proliferation rate of 48%

Lunasin – a bioactive peptide from triticale (X Triticosecale Wittmack ) seeds, inhibits proliferation of cancer HeLa and SK-OV-3 cells

The presented study demonstrates the influence of lunasin, a bioactive peptide isolated from seeds of winter triticale, on the proliferation of neoplastic cells. In order to conduct investigations, 2S fraction low-molecular-weight albumin proteins were extracted. SDS-PAGE electrophoresis separation of extracts indicated the presence of a 5 kDa peptide in the crude extract, which corresponded to the weight of lunasin. The next stage of protein purification involved ion-exchange column chromatography in an FPLC system on DEAE Sepharose Fast Flow. The separation of biomolecules by means of 2D electrophoresis confirmed that a peptide with an isoelectric point was present in the area, with a pH of about 5.5 and molecular mass of about 5 kDa. The presence of lunasin in the purified samples was confirmed by Western blot. The lunasin peptide affected the proliferation of cervical cancer (HeLa) and ovarian cancer (SK-OV-3) cell lines. The average decrease in the HeLa cell proliferation rate was 17%. The SK-OV-3 cell line was more susceptible to inhibition by the protein fraction containing lunasin than HeLa cells, with an average decrease in the proliferation rate of 48%

Association analysis of vitamin D receptor gene polymorphisms with bone mineral density in young women with Graves' disease

Graves' (GD) hyperthyroidism induces accelerated bone turnover that leads to decreased bone mineral density (BMD). The role of the VDR gene in predisposition to primary osteoporosis has been recognized. Recent studies show associations between the VDR gene polymorphisms and susceptibility to autoimmune diseases. Here we analyzed if VDR gene polymorphisms: BsmI, ApaI, TaqI, and FokI may predispose women with Graves' hyperthyroidism to BMD reduction or to disease development. The subjects were 75 premenopausal female Polish patients with GD and 163 healthy women. The genotyping was performed by the use of the restriction fragment length polymorphism analysis (RFLP). We studied the association of the VDR polymorphisms and their haplotypes with patients' BMD and also SNPs and haplotypes association with Graves' disease. We found a strong linkage disequilibrium for the BsmI, ApaI, and TaqI polymorphims that formed three most frequent haplotypes in Graves' women: baT (47.9%), BAt (34.9%), and bAT (16.4%). We did not show statistically significant association of analyzed VDR polymorphisms or haplotypes with decreased bone mineral density in Graves' patients. However, the presence of F allele had a weak tendency to be associated with Graves' disease (with OR=1.93; 95% CI: 0.97-3.84; p=0.058). In conclusion: VDR gene polymorphisms do not predict the risk of decreased BMD in Polish women with Graves'. It may be speculated that the F allele carriers of the VDR-FokI polymorphism are predisposed to Graves' disease development