Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.

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Objective Implantation of tissue-engineered tracheal grafts represents a visionary strategy for the reconstruction of tracheal wall defects after resections and may develop into a last chance for a number of patients with severe cicatricial stenosis. The use of a decellularized tracheal substrate would offer an ideally stiff graft, but the matrix density would challenge efficient remodeling into a living cartilage. In this study, we hypothesized that the pores of decellularized laser-perforated tracheal cartilage (LPTC) tissues can be colonized by adult nasal chondrocytes (NCs) to produce new cartilage tissue suitable for the repair of tracheal defects. Design Human, native tracheal specimens, isolated from cadaveric donors, were exposed to decellularized and laser engraving–controlled superficial perforation (300 μm depth). Human or rabbit NCs were cultured on the LPTCs for 1 week. The resulting revitalized tissues were implanted ectopically in nude mice or orthotopically in tracheal wall defects in rabbits. Tissues were assayed histologically and by microtomography analyses before and after implantation. Results NCs were able to efficiently colonize the pores of the LPTCs. The extent of colonization (i.e., percentage of viable cells spanning >300 μm of tissue depth), cell morphology, and cartilage matrix deposition improved once the revitalized constructs were implanted ectopically in nude mice. LPTCs could be successfully grafted onto the tracheal wall of rabbits without any evidence of dislocation or tracheal stenosis, 8 weeks after implantation. Rabbit NCs, within the LPTCs, actively produced new cartilage matrix. Conclusion Implantation of NC-revitalized LPTCs represents a feasible strategy for the repair of tracheal wall defects.

This article reports the electrospinning technique for the manufacturing of multilayered scaffolds for bile duct tissue engineering based on an inner layer of polycaprolactone (PCL) and an outer layer either of a copolymer of D,L-lactide and glycolide (PLGA) or a copolymer of L-lactide and ε-caprolactone (PLCL). A study of the degradation properties of separate polymers showed that flat PCL samples exhibited the highest resistance to hydrolysis in comparison with PLGA and PLCL. Irrespective of the liquid-phase nature, no significant mass loss of PCL samples was found in 140 days of incubation. The PLCL- and PLGA-based flat samples were more prone to hydrolysis within the same period of time, which was confirmed by the increased loss of mass and a significant reduction of weight-average molecular mass. The study of the mechanical properties of developed multi-layered tubular scaffolds revealed that their strength in the longitudinal and transverse directions was comparable with the values measured for a decellularized bile duct. The strength of three-layered scaffolds declined significantly because of the active degradation of the outer layer made of PLGA. The strength of scaffolds with the PLCL outer layer deteriorated much less with time, both in the axial (p-value = 0.0016) and radial (p-value = 0.0022) directions. A novel method for assessment of the physiological relevance of synthetic scaffolds was developed and named the phase space approach for assessment of physiological relevance. Two-dimensional phase space (elongation modulus and tensile strength) was used for the assessment and visualization of the physiological relevance of scaffolds for bile duct bioengineering. In conclusion, the design of scaffolds for the creation of physiologically relevant tissue-engineered bile ducts should be based not only on biodegradation properties but also on the biomechanical time-related behavior of various compositions of polymers and copolymers.

На экспериментальной модели хронического фиброзирующего повреждения печени (крысы-самцы породы Вистар (n=60), затравка CCl 4 , длительность эксперимента 90 суток) изучена эффективность клеточной терапии при коррекции хронической печеночной недостаточности. Выполнено 3 группы опытов: I группа (n=10)-контрольная (введение физиологического раствора); II группа (n=20)-введение в печень суспензии клеток донорской печени в дозе 8-10×10 6 клеток; III группа (n=30)-введение в печень ассоциатов клеток донорской печени и донорских мультипотентных мезенхимальных стромальных клеток костного мозга в соотношении 5:1 и в суммарной дозе 8-10×10 6 клеток на микрочастицах инъекционного гетерогенного биополимерного гидрогеля СфероГЕЛЬ (клеточно-инженерные конструкции). Установлено, что клеточная терапия во II и III группах опытов способствовала достоверно ускоренной нормализации нарушенных функций печени: к 30-м суткам вместо 90-х суток в контроле (I группа). При этом достоверные различия в темпе нормализации функциональных показателей печени во II и III группах отсутствовали. Однако гистологический анализ показал, что через 90 суток темп дефиброзирования ткани печени в III группе был существенно более выражен, чем во II группе. Полученный эффект можно объяснить тем, что разработанные клеточно-инженерные конструкции обеспечивают адекватные условия для пролонгированной жизнедеятельности трансплантированных клеток. Ключевые слова: печеночная недостаточность, клеточная терапия, клеточно-инженерные конструкции.

A growing number of studies report dermal malignancies mimicking diabetic foot ulcers (DFUs). We reviewed clinical cases reporting malignant tumours misdiagnosed to be DFU aiming to identify factors contributing to misdiagnosis. We systematically searched in PubMed for clinical cases reporting on misdiagnosis of DFU in patients with cancer. A chi-square analysis was conducted to show the link between the incidence of initial DFU misdiagnosis and patient age, gender and wound duration. Lesions misdiagnosed to be DFU were subsequently diagnosed as melanoma (68% of the cases), Kaposi's sarcoma (14%), squamous cell carcinoma (11%), mantle cell lymphoma, and diffuse B-cell lymphoma (both by 4%). Older age (≥65 years) was associated with a significantly increased risk of malignancy masked as DFU (OR: 2.452; 95% CI: 1.132 to 5.312; P value = .019). The risk of such suspicion in older patients (age ≥ 65 years) was 145% higher than in younger patients (age < 65 years).Clinicians should maintain a high level of awareness towards potentially malignant foot lesions in elderly patients with diabetes (age ≥ 65).diabetic foot ulcer, malignancy, melanoma, misdiagnosis, skin cancer Key Messages• reports of diabetic foot ulcer (DFU) are increasing in number, and there are several accounts of malignancies misdiagnosed as DFU • the vast majority of malignancies misdiagnosed as DFU are melanomas (71%) • patients at ages above 65 years have more than twice (Â2.5) higher chance of DFU misdiagnosis

Обзор посвящен истории создания тканеинженерных конструкций, применяемых в хирургическом лечении различных заболеваний в гинекологии и урогинекологии. Приведены основные принципы, возможности, преимущества и недостатки разработок по лечению пролапса тазовых органов, синдрома недержания мочи и частичному органозамещению с применением клеточных структур. Описаны результаты работ, опубликованные за последние 15 лет, в которых определяются чувствительность и специфичность тканеинженерных конструкций на примере лабораторных животных. Этот обзор подчеркивает достижения в тканеинженерных технологиях для проведения регенерации сложных тканей и органов, а также позволяет судить о важности данных инновационных разработок для клиники. Авторы информируют об отсутствии конфликта интересов.

Objective: to study the effectiveness of correcting the morphofunctional characteristics of the liver in an experimental model of chronic liver disease (CLD), using implanted cell-engineered constructs (CECs).Materials and methods. Experiments were carried out on male Wistar rats (n = 80) aged 6–8 months with an initial weight of 230–250 g. CLD was modeled by inoculating the rats with 60% CCl4 oil solution for 42 days based on a modified scheme. Microgel based on recombinant spidroin rS1/9 was used as a matrix for CECs fabrication. Allogeneic liver cells (LCs) and multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) from a healthy donor were used as the cellular component of the CECs. The effectiveness of the corrective effect of the implanted CECs was assessed in an experimental CLD model (n = 60) in two groups of rats: Group 1 (control, n = 20, 1 mL of saline solution was injected into the damaged liver parenchyma) and Group 2 (experimental, n = 40, CECs containing allogenic LCs and BM-MSCs in a 5 : 1 ratio in a volume of 1 mL were implanted into the damaged liver parenchyma). For long-term monitoring of the CEC state, the CECs were labeled by additional inclusion in Cytodex-3. The effectiveness of the regulatory effect of CECs on regenerative processes in the liver was evaluated using biochemical, morphological and morphometric techniques, as well as by flow cytometry at 90 days after implantation.Results. In the control group, the mortality rate in CLD was 25%. There was no death in the experimental group with CLD after CEC implantation. The CECs were found to have a corrective effect on the biochemical and morphological parameters of the liver in CLD during 90 days of follow-up, with concomitant preservation of structural cellular homeostasis in the implanted CECs. Conclusion. Implantation of CECs in the liver facilitates effective correction of CLD by activating regenerative processes in the damaged liver, which is due to long-term preservation of structural cellular homeostasis in the CECs.