Isolated liver chemo perfusion for hepatic metastases from uveal melanoma: a report of 38 cases.

Aim: To evaluate the outcomes of isolated liver chemo perfusion in patients with hepatic metastases from uveal melanoma. Materials and methods: Cardiovascular surgeons are often involved in the treatment of oncological diseases. Isolated liver chemoperfusion requires the use a heart-lung machine. A little more than 300 operations of isolated liver chemoperfusion have been performed worldwide. From 2020 to 2023, 38 cases of isolated liver chemoperfusion were performed at the Kostroma Clinical Oncological Dispensary. Results: There were 3 deaths, 2 due to liver failure. The remaining patient had hepatic artery thrombosis, who despite emergency thrombectomy and repair of common hepatic artery succumbed to multiorgan failure. Bleeding was diagnosed in 7 patients in the postoperative period. In all cases, relaparotomy was performed to stop bleeding. Subsequently, no special features were noted. The median disease-free survival was 5.4 months. The median overall survival was 20.3 months at the time of submission of this manuscript. Conclusions: Isolated liver chemoperfusion is a safe method of regional chemotherapy and can be considered in patients with isolated hepatic metastases from uveal melanoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01620-6.

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic188Re radionuclide for nuclear medicine.

Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH2MOFs and conjugated them with clinically utilized radionuclide188Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq mg-1. Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was (20.9 ± 1.3) h, and nanoparticles enabled it to passively accumulate and retain in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH2for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine.

Properties and Printability of the Synthesized Hydrogel Based on GelMA.

Gelatin methacryloyl (GelMA) has recently attracted increasing attention. Unlike other hydrogels, it allows for the adjustment of the mechanical properties using such factors as degree of functionalization, concentration, and photocrosslinking parameters. In this study, GelMA with a high degree of substitution (82.75 ± 7.09%) was synthesized, and its suitability for extrusion printing, cytocompatibility, and biocompatibility was studied. Satisfactory printing quality was demonstrated with the 15% concentration hydrogel. The high degree of functionalization led to a decrease in the ability of human adipose-derived stem cells (ADSCs) to adhere to the GelMA surface. During the first 3 days after sowing, proliferation was observed. Degradation in animals after subcutaneous implantation was slowed down.

Octahedra-Tilted Control of Displacement Disorder and Dielectric Relaxation in Mn-Doped SrTiO3 Single Crystals.

Strontium titanate SrTiO3 (STO) is a canonical example of a quantum paraelectric, and its doping with manganese ions unlocks its potential as a quantum multiferroic candidate. However, to date, the specifics of incorporation of the manganese ion into the perovskite lattice and its impact on structure-property relationships are debatable questions. Herein, using high-precision X-ray diffraction of a Mn (2 atom %)-doped STO single crystal, clear fingerprints of the displacement disorder of Mn cations in the perovskite B-sublattice are observed. Moreover, near the temperature of the antiferrodistortive transition, the off-center Mn position splits in two, providing the unequal potential barrier's distribution for possible local atomic hopping. A link with this was found via analysis of the dielectric response that reveals two Arrhenius-type relaxation processes with similar activation energies (35 and 43 meV) and attempt frequencies (1 × 1011 and ∼1.6 × 1010 Hz), suggesting similar dielectric relaxation mechanisms.

Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ.

Transfer of regenerative approaches into clinical practice is limited by strict legal regulation of in vitro expanded cells and risks associated with substantial manipulations. Isolation of cells for the enrichment of bone grafts directly in the Operating Room appears to be a promising solution for the translation of biomedical technologies into clinical practice. These intraoperative approaches could be generally characterized as a joint concept of tissue engineering in situ. Our review covers techniques of intraoperative cell isolation and seeding for the creation of tissue-engineered grafts in situ, that is, directly in the Operating Room. Up-to-date, the clinical use of tissue-engineered grafts created in vitro remains a highly inaccessible option. Fortunately, intraoperative tissue engineering in situ is already available for patients who need advanced treatment modalities.

On the Pathomorphological Pattern of the Efficiency of Photodynamic Therapy of Murine Melanoma B16 Using a New Photosensitizer Based on Chlorin e6 Conjugate with a Prostate-Specific Membrane Antigen.

Photodynamic therapy (PDT) is an effective treatment for a number of solid malignancies. In this work, the antitumor efficacy of photodynamic therapy for murine B16 melanoma with intravenous administration of a new photosensitizer (PS) based on the chlorin e6 conjugate with a prostate-specific membrane antigen (PSMA) was studied in vivo. We have previously published the data obtained in the first part of the study: the dynamics of PS accumulation in the tumor and surrounding tissues and the antitumor efficacy of the photodynamic therapy, which was evaluated by the regression parameters and morphological characteristics of the tumors-including by the complete regression of the tumors, the absolute growth rate of the tumors among the mice with continued tumor growth, and an increase in life expectancy compared to the control. The criterion for a complete cure was the absence of signs of tumor recurrence within 90 days after therapy. The conducted studies demonstrated the high efficiency of the new photosensitizer for the photodynamic therapy of B16 melanoma. This article presents a continuation of this work, including histological studies of the zones exposed to laser irradiation on the 21st day after treatment and an assessment of the therapeutic potential of photodynamic therapy for the destruction of tumor cells. Pathological studies in the zones of photodynamic exposure revealed that the effectiveness of the PDT depended on the PS dose and the laser irradiation parameters.

Cartilage Formation In Vivo Using High Concentration Collagen-Based Bioink with MSC and Decellularized ECM Granules.

The aim of this study was to verify the applicability of high-concentration collagen-based bioink with MSC (ADSC) and decellularized ECM granules for the formation of cartilage tissue de novo after subcutaneous implantation of the scaffolds in rats. The printability of the bioink (4% collagen, 2.5% decellularized ECM granules, derived via 280 µm sieve) was shown. Three collagen-based compositions were studied: (1) with ECM; (2) with MSC; (3) with ECM and MSC. It has been established that decellularized ECM granules are able to stimulate chondrogenesis both in cell-free and MSC-laden scaffolds. Undesirable effects have been identified: bone formation as well as cartilage formation outside of the scaffold area. The key perspectives and limitations of ECM granules (powder) application have been discussed.

Complex correlations between microstructure and magnetic behavior in SrFe12O19 hexaferrite nanoparticles.

The magnetic properties of SrFe12O19 (SFO) hard hexaferrites are governed by the complex relation to its microstructure, determining their relevance for permanent magnets´ applications. A set of SFO nanoparticles obtained by sol-gel self-combustion synthesis was selected for an in-depth structural X-Rays powder diffraction (XRPD) characterization by means of G(L) line-profile analysis. The obtained crystallites´ size distribution reveal a clear dependence of the size along the [001] direction on the synthesis approach, resulting in the formation of platelet-like crystallites. In addition, the size of the SFO nanoparticles was determined by transmission electron microscopy (TEM) analysis and the average number of crystallites within a particle was estimated. These results have been evaluated to illustrate the formation of single-domain state below a critical value, and the activation volume was derived from time dependent magnetization measurements, aiming to clarify the reversal magnetization process of hard magnetic materials.

Bioprinting of Cartilage with Bioink Based on High-Concentration Collagen and Chondrocytes.

The study was aimed at the applicability of a bioink based on 4% collagen and chondrocytes for de novo cartilage formation. Extrusion-based bioprinting was used for the biofabrication. The printing parameters were tuned to obtain stable material flow. In vivo data proved the ability of the tested bioink to form a cartilage within five to six weeks after the subcutaneous scaffold implantation. Certain areas of cartilage formation were detected as early as in one week. The resulting cartilage tissue had a distinctive structure with groups of isogenic cells as well as a high content of glycosaminoglycans and type II collagen.

Micronectagriseola Horvath, 1899 - a new species of the family Corixidae (Heteroptera) for the fauna of the Middle Urals.

BACKGROUND: Micronecta (Micronecta) griseola Horvath, 1899 is a representative of water bugs of the family Corixidae. It is expanding its range eastwards according to our observations in Russia. In the last decade, the species has become more common in Western Siberia. NEW INFORMATION: The article presents the first records of M.griseola from the territory of the Middle Urals (Russia). The distribution of the species and the features of its biology are considered.

Evolution of Griffiths phase and critical behaviour of La1-x Pb x MnO3±y solid solutions.

Polycrystalline La1-x Pb x MnO3±y (x = 0.3, 0.35, 0.4) solid solutions were prepared by solid state reaction method and their magnetic properties have been investigated. Rietveld refinement of x-ray powder diffraction patterns showed that all samples are single phase and crystallized with the rhombohedral structure in the R-3c space group. A second order paramagnetic to ferromagnetic (FM) phase transition was observed for all materials. The Griffiths phase (GP), identified from the temperature dependence of the inverse susceptibility, was suppressed by increasing magnetic field and showed a significant dependence on A-site chemical substitution. The critical behaviour of the compounds was investigated near to their Curie temperatures, using intrinsic magnetic field data. The critical exponents (ß, γ and δ) are close to the mean-field approximation values for all three compounds. The observed mean-field like behaviour is a consequence of the GP and the formation of FM clusters. Long-range FM order is established as the result of long-range interactions between FM clusters. The magnetocaloric effect was studied in terms of the isothermal entropy change. Our study shows that the material with the lowest chemical substitution (x = 0.3) has the highest potential (among the three compounds) as magnetic refrigerant, owing to its higher relative cooling power (258 J kg-1 at 5 T field) and a magnetic phase transition near room temperature.

Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival.

The outer membrane is a key virulence determinant of gram-negative bacteria. In Yersinia pestis, the deadly agent that causes plague, the protein Ail and lipopolysaccharide (LPS)6 enhance lethality by promoting resistance to human innate immunity and antibiotics, enabling bacteria to proliferate in the human host. Their functions are highly coordinated. Here we describe how they cooperate to promote pathogenesis. Using a multidisciplinary approach, we identify mutually constructive interactions between Ail and LPS that produce an extended conformation of Ail at the membrane surface, cause thickening and rigidification of the LPS membrane, and collectively promote Y. pestis survival in human serum, antibiotic resistance, and cell envelope integrity. The results highlight the importance of the Ail-LPS assembly as an organized whole, rather than its individual components, and provide a handle for targeting Y. pestis pathogenesis.

Radioprotective Activity of the Nitric Oxide Synthase Inhibitor T1023. Toxicological and Biochemical Properties, Cardiovascular and Radioprotective Effects.

In this work, studies were performed to investigate the toxicological, biochemical, vasotropic and radiomodifying properties of the new nitric oxide synthase (NOS) inhibitor, compound T1023. Toxicological studies included the estimation of acute toxicity in mice after i.p. administration of T1023. Radiometric analysis and electron paramagnetic resonance spectroscopy were used to study NOS-inhibitory properties of T1023 in vitro and in vivo, respectively. T1023 vasoactive properties were studied in rat central hemodynamics. Radiobiological experiments were performed using endogenous and exogenous spleen colony formation as well as 30-day survival tests. The morphological changes in peripheral blood and bone marrow (BM) induced with T1023 were analyzed in mice during hematopoietic acute radiation syndrome (H-ARS). It was shown that T1023 is a sufficiently safe compound (LD10 of 317 mg/kg; LD50 of 410 mg/kg). It is an effective competitive NOS-inhibitor that is 10-to-15-fold selective to endothelial and inducible NOS (IC50 for nNOS, iNOS, eNOS: 52.3, 3.2 and 5.1 µM, respectively). Its NOS-inhibitory activity is realized in vivo and is accompanied by an increase in vascular tone. Its single i.p. administration in doses greater than 1/8 LD10 provides significant (40-50%) and long-lasting (more than 90 min) weakening of cardiac output, which can cause transient hypoxia. In radiobiological studies, T1023 proved to be a hypoxic radioprotector. Its radioprotective effect was observed only when administered prophylactically [single i.p dose, 5-120 min before total-body irradiation (TBI)] and only in doses that reduced cardiac output (1/8 LD10 and more, 40 mg/kg for mice), and was correlated in time with the dynamics of circulatory depression. Its radioprotective effect was not observed when administered in vitro and in the first 4 h after TBI. The optimal radioprotective doses of T1023 are relatively safe (1/ 5-1/4 LD10). In addition, T1023 effectively prevents H-ARS and gastrointestinal acute radiation syndrome (G-ARS) in experimental animals in vivo: dose modifying factor of 1.6-1.9. In the H-ARS mouse model, the prophylactic effect of T1023 (75 mg/kg, single i.p. injection) was accompanied by clinically significant effects. There was an express decrease in the degree of indicators of early BM devastation (by 40%) and maximal neutropenia and thrombocytopenia (2-2.5 times), in addition to a reduction in recovery time (by 30-40%). The obtained experimental results and literature data indicate that NOS inhibitors are an independent class of vasoactive radioprotectors with a specific hypoxic mechanism of action. NOS inhibitors provide new opportunities for developing effective and safe tools for the prevention of ARS.

Two Isoforms of Yersinia pestis Plasminogen Activator Pla: Intraspecies Distribution, Intrinsic Disorder Propensity, and Contribution to Virulence.

It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of the C-terminal tail of Pla and makes this protein slightly more prone for disorder-based protein-protein interactions, suggesting that the T259 Pla could be functionally more active than the I259 Pla. This assumption was proven experimentally by assessing the coagulase and fibrinolytic activities of the two Pla isoforms in human plasma, as well as in a direct fluorometric assay with the Pla peptide substrate. The virulence testing of Pla-negative or expressing the I259 and T259 Pla isoforms Y. pestis subsp. microtus and subsp. pestis strains did not reveal any significant difference in LD50 values and dose-dependent survival assays between them by using a subcutaneous route of challenge of mice and guinea pigs or intradermal challenge of mice. However, a significant decrease in time-to-death was observed in animals infected with the epidemic T259 Pla-producing strains as compared to the parent Pla-negative variants. Survival curves of the endemic I259 Pla+ strains fit between them, but significant difference in mean time to death post infection between the Pla-strains and their I259 Pla+ variants could be seen only in the isogenic set of subsp. pestis strains. These findings suggest an essential role for the outer membrane protease Pla evolution in Y. pestis bubonic infection exacerbation that is necessary for intensification of epidemic process from endemic natural focality with sporadic cases in men to rapidly expanding epizootics followed by human epidemic outbreaks, local epidemics or even pandemics.

Yersinia pestis Caf1 Protein: Effect of Sequence Polymorphism on Intrinsic Disorder Propensity, Serological Cross-Reactivity and Cross-Protectivity of Isoforms.

Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the Caf1 proteins exist in three isoforms, the global type Caf1NT1 (Ala48 Phe117), type Caf1NT2 (Ser48 Phe117) found in Transcaucasian-highland and Pre-Araks natural plague foci #4-7, and a novel Caf1NT3 type (Ala48 Val117) endemic in Dagestan-highland natural plague focus #39. Both minor types are the progenies of the global isoform. In this report, Caf1 polymorphism was analyzed by comparing predicted intrinsic disorder propensities and potential protein-protein interactivities of the three Caf1 isoforms. The analysis revealed that these properties of Caf1 protein are minimally affected by its polymorphism. All protein isoforms could be equally detected by an immunochromatography test for plague at the lowest protein concentration tested (1.0 ng/mL), which is the detection limit. When compared to the classic Caf1NT1 isoform, the endemic Caf1NT2 or Caf1NT3 had lower immunoreactivity in ELISA and lower indices of self- and cross-protection. Despite a visible reduction in cross-protection between all Caf1 isoforms, our data suggest that polymorphism in the caf1 gene may not allow the carriers of Caf1NT2 or Caf1NT3 variants escaping from the Caf1NT1-mediated immunity to plague in the case of a low-dose flea-borne infection.

Polar Order and Frustrated Antiferromagnetism in Perovskite Pb2MnWO6 Single Crystals.

Single crystals of the multiferroic double-perovskite Pb2MnWO6 have been synthesized and their structural, thermal, magnetic and dielectric properties studied in detail. Pure perovskite-phase formation and stoichiometric chemical composition of the as-grown crystals are confirmed by X-ray single-crystal and powder diffraction techniques as well as energy-dispersive X-ray and inductively coupled plasma mass spectrometry. Detailed structural analyses reveal that the crystals experience a structural phase transition from the cubic space group (s.g.) Fm3̅m to an orthorhombic structure in s.g. Pn21a at about 460 K. Dielectric data suggest that a ferrielectric phase transition takes place at that same temperature, in contrast to earlier results on polycrystalline samples, which reported a transition to s.g. Pnma and an antiferroelectric low-temperature phase. Magnetic susceptibility measurements indicate that a frustrated antiferromagnetic phase emerges below 8 K. Density functional theory based calculations confirm that the cationic order between Mn and W is favorable. The lowest total energy was found for an antiferromagnetically ordered state. However, analyses of the calculated exchange parameters revealed strongly competing antiferromagnetic interactions. The large distance between the magnetic atoms, together with magnetic frustration, is shown to be the main reason for the low value of the ordering temperature observed experimentally. We discuss the structure-property relationships in Pb2MnWO6 and compare these observations to reported results on related Pb2BWO6 perovskites with different B cations.

Structure of a zwitterionic O-polysaccharide from Photorhabdus temperata subsp. cinerea 3240.

A phosphorylated O-polysaccharide was isolated from the lipopolysaccharide of an entomopathogenic bacterium Photorhabdus temperata subsp. cinerea 3240 and studied by sugar analysis, dephosphorylation, and (1)H and (13)C NMR spectroscopy. The following structure of the linear trisaccharide repeating unit of the O-polysaccharide was established: →3)-ß-D-GalpNAc4PEtN-(1→4)-ß-D-GlcpA-(1→3)-ß-D-FucpNAc4N-(1→ where GlcA indicates glucuronic acid, FucNAc4N 2-acetamido-4-amino-2,4,6-trideoxygalactose, and PEtN 2-aminoethyl phosphate.

Structure of the O-polysaccharide of Photorhabdus temperata subsp. temperata XlNach(T) containing a novel branched monosaccharide, 3,6-dideoxy-4-C-[(S)-1,2-dihydroxyethyl]-d-xylo-hexose.

O-Polysaccharide was isolated from the lipopolysaccharide of an entomopathogenic bacterium Photorhabdus temperata subsp. temperata XlNach(T). Sugar analysis after full acid hydrolysis of the polysaccharide revealed D-glucose, D-mannose, D-galactose, D-GalNAc, and a branched monosaccharide, 3,6-dideoxy-4-C-[(S)-1',2'-dihydroxyethyl]-D-xylo-hexose (Sug), which was isolated as a 1,2'-anhydro furanose derivative. The following structure of the polysaccharide was established by 1D and 2D 1H and 13C NMR spectroscopy:

Structure of the O-polysaccharide of Photorhabdus luminescens subsp. laumondii containing D-glycero-D-manno-heptose and 3,6-dideoxy-3-formamido-D-glucose.

The O-polysaccharide from the lipopolysaccharide of a symbiotic bacterium Photorhabdus luminescens subsp. laumondii TT01 from an insect-pathogenic nematode was studied by sugar analysis and (1)H and (13)C NMR spectroscopy and found to contain D-glycero-D-manno-heptose (DDHep) and 3,6-dideoxy-3-formamido-D-glucose (D-Qui3NFo). The following structure of the pentasaccharide repeating unit of the O-polysaccharide was established:

Glutinoin, a novel antioxidative ellagitannin from Alnus glutinosa cones with glutinoic acid dilactone moiety.

The crude aqueous ethanol extract of the cones of Alnus glutinosa (L.) Gaertn. (Betulaceae; black alder, European alder) was obtained and further partitioned between water and various organic phases. The active water and butanol phases were subjected to assay-guided (DPPH) fractionation using repetitive RP HPLC until individual compounds were isolated. Their antioxidative activities, measured as SC50 values, were evaluated. The chemical structures of the isolated compounds were elucidated with the help of mass spectroscopy, (1)H NMR technique, UV spectroscopy, and chemical approaches. One novel ellagitannin, glutinoin (2), along with two known compounds, pedunculagin (1) and praecoxin D (3), were isolated and found to contribute to antioxidative activity of the A. glutinosa cones extract. The activities (SC50) of 1-3 were evaluated as 0.95 (1), 1.00 (2) and 1.01 µg mL⁻¹ (3). The scavenging effects of glutinoin (2) and praecoxin D (3) were reported for the first time.