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HPV infection is involved in the etiology of a number of nonmalignant, premalignant and malignant cutaneous lesions. One of them is the so-called giant condyloma of Buschke-Löwenstein type (Buschke-Löwenstein tumor, BLT), which sometimes can imitate clinically other tumors or tumor-like conditions. Clinicians face a particular challenge in cases of BLT where, clinically, the lesions demonstrate a permanent brown hyperpigmentation in parallel with the dermatoscopic lack of the characteristic melanocytic network, globules or regression zones. There are uncommon clinical presentations with solitary, sharply demarcated pigmented lesions. In these cases the histopathological verification of the lesion is obligatory and the most efficient treatment method in the early period of the disease is the complete surgical excision. We report a case of a 74-year-old man who was admitted to the University Hospital “Lozenetz” in connection with profuse variceal bleeding of the esophagus associated with liver cirrhosis of unknown etiology. He underwent a consultative examination at the department of dermatology because of suspected advanced stage melanoma of the prepuce. Computed tomographic analysis indicated diffuse bone metastases located in the small pelvis and femur, as well as metastatic disease in the left inguinal lymph nodes. However, the subsequent histopathologic examination of the lesion, rather than showing melanoma, confirmed the presence of HPV-associated giant condyloma of Buschke and Löwenstein in initial stage, without histopathological evidence for invasive and destructive tumor growth. After his death, the patient’s relatives did not give consent for an autopsy, and therefore the genesis of the metastases, demonstrated by nuclear magnetic resonance imaging (NMR), remained unclear. In some cases, the clinical picture of the malignant and premalignant cutaneous lesions in the genital area could be problematic. The complete surgical excision with a subsequent histopathological verification is the best way to find out the exact diagnosis

Basal cell carcinoma (BCC) is the most frequent non-melanoma skin cancer. Only 5-15% of BCC cases can be found in patients aged 20-40 years (so-called early onset). The early onset BCC is characterized by active and aggressive tumour growth, clinically presenting in most of the cases as a morpheaform, locally infiltrating or recurrent BCC. Despite the advances in the study of the pathogenesis of this tumour, surgery remains the most used, most effective and most suitable treatment modality. We describe a case of a 39-year-old woman who developed an early onset BCC of the nasolabial fold. After the subsequent surgical excision an excellent cosmetic result was achieved.

The crude alkaloid mixtures from the aerial parts S.telephium was analyzed by GC-MS method. As a result 14 compounds, including 6 alkaloids were characterized. 3-methyl-2-carbethoxyindole (4.730%), 2-(2-hydroxyphenyl) benzothiazole (1.576%) and N,4, 5-trimethyl phenyl-1,2-diamine, (1.217%) were in higher contents. One sulfur-containing alkaloid 2-(2-hydroxyphenyl) benzothiazole has been identified. These six alkaloids are described for the first time from this plant. [ABSTRACT FROM AUTHOR]

3-methyl-1,2,3,4-tetrahydroquinoline (1), 4-hydroxyisoquinoline (2), 4-(1E)-hydroxy-1-prophenyl)-2-methoxyphenol (3), 4-acetoxycinnamic acid (4), Songoramine (5), and Songorine (6) have been determined by GC-MS analysis from the crude alkaloid mixtures (G1) obtained from the aerial parts of Lagochilus ilicifolius Bge. grown in Mongolia and comparison of the measured data with those from the literature. The compounds 1-6 are described for the first time from L.ilicifolius. From these 3-methyl-1,2,3,4-tetrahydroquinoline (1) was determined for the first time from natural plants. In addition, the antibacterial activity of fractions and total alkaloids were evaluated against Staphylococcus aurous, Bacillus subtilis, Bacillus cereus and Escherichia coli strains, respectively. The growth inhibition zones against gram-positive S.aureus, B.subtilis, B.cereus and gram negative E.coli, strains were observed. Positive results were achieved on 500 μg/ disc concentration, but lower results or no active on 100 μg/disc concentration were for the plant extracts, fractions and total alkaloids. [ABSTRACT FROM AUTHOR]

Alkaloids of the aerial parts of P. multisectum (Maxim) Bobrov (Zygophyllaceae) growing in Mongolia have been studied by capillary Gas Chromatography-Mass Spectrometry (GC-MS) and Column Chromatography (CC). Four compounds comprising of 2-methylquinoline (1), 9-amino-2, 3,5,6,7,8-hexahydro-1H-cyclopenta [b] quinoline (2), vasicinone (3) and harmine (4) have been determined by GC-MS, while harmine (4), peganine (5), deoxypeganine (6), deoxyvasicinone (7) and harmane (8) were isolated as pure compounds by the CC. The structures of the five alkaloids 4, 5, 6, 7 and 8 were elucidated by the MS and 1H and 13C NMR analysis. The alkaloids 1, 2 and 8 were identified for the first time from this species. [ABSTRACT FROM AUTHOR]

The rise in highway design and construction requires ensuring the reliability of these infrastructure projects. This is especially important for construction on weak soils. The number of design solutions is equally on the rise for reinforcing the grounds of soil transport structures. Examples include the use of various types of piles, and structures made of sand, gravel and other draining soils placed in a shell of geosynthetic material. The article presents the results of the authors' work on the substantiation and implementation of various constructive solutions to strengthen the insufficiently strong bases on railway and highway construction facilities (railway lines Losevo-Kamennogorsk, Moscow-Kazan high-speed railroad, Moscow-Saint Petersburg high-speed highway, etc.).

Coronaviruses (CoVs) belong to the group of enveloped positive-sense single-strand RNA viruses and are causative agents of respiratory, gastro-intestinal, and central nervous systems diseases in many host species, i.e., birds, mammals, and humans. Beta-CoVs revealed a great potential to cross the barrier between species by causing three epidemics/pandemics among humans in the 21st century. Considering the urgent need for powerful antiviral agents for decontamination, prevention, and treatment of BCoV infections, we turned our attention to the possibility of photodynamic inactivation with photosensitizers in combination with light irradiation. In the present study, we evaluated, for the first time, the antiviral activity of toluidine blue O (TBO) against Beta-coronavirus 1 (BCoV) in comparison to methylene blue (MB). First, we determined the in vitro cytotoxicity of MB and TBO on the Madin-Darby bovine kidney (MDBK) cell line with ISO10993-5/Annex C. Thereafter, BCoV was propagated in MDBK cells, and the virus titer was measured with digital droplet PCR, TCID 50 assay and plaque assay. The antiviral activity of non-toxic concentrations of TBO was estimated using the direct inactivation approach. All effects were calculated in MAPLE 15 ® mathematical software by developing programs for non-linear modeling and response surface analysis. The median inhibitory concentration ( IC 50 ) of TBO after 72 h of incubation in MDBK cells was 0.85 µM. The antiviral activity of TBO after the direct inactivation of BCoV ( MOI = 1) was significantly stronger than that of MB. The median effective concentration (EC 50 ) of TBO was 0.005 µM. The cytopathic effect decreased in a concentration-dependent manner, from 0.0025 to 0.01 µM, and disappeared fully at concentrations between 0.02 and 0.3 µM of TBO. The number of virus particles also decreased, depending on the concentration applied, as proven by ddPCR analysis. In conclusion, TBO exhibits significant potential for direct inactivation of BCoV in vitro, with a very high selectivity index, and should be subjected to further investigation, aiming at its application in veterinary and/or human medical practice.

Tuberculosis (TB) remains a widespread infectious disease and one of the top 10 causes of death worldwide. Nevertheless, despite significant advances in the development of new drugs against tuberculosis, many therapies and preventive measures do not lead to the expected favorable health results for various reasons. The aim of this study was to evaluate the acute and sub-acute toxicity and oxidative stress of two selected nitrofuranyl amides with high in vitro antimycobacterial activity. In addition, molecular docking studies were performed on both compounds to elucidate the possibilities for further development of new anti-tuberculosis candidates with improved efficacy, selectivity, and pharmacological parameters. Acute toxicity tests showed that no changes were observed in the skin, coat, eyes, mucous membranes, secretions, and vegetative activity in mice. The histological findings include features consistent with normal histological architecture without being associated with concomitant pathological conditions. The observed oxidative stress markers indicated that the studied compounds disturbed the oxidative balance in the mouse liver. Based on the molecular docking, compound DO-190 showed preferable binding energies compared to DO-209 in three out of four targets, while both compounds showed promising protein-ligand interactions. Thus, both studied compounds displayed promising activity with low toxicity and can be considered for further evaluation and/or lead optimization.

The difficult-to-heal wounds continue to be a problem for modern medicine. Chitosan and diosgenin possess anti-inflammatory and antioxidant effects making them relevant substances for wound treatment. That is why this work aimed to study the effect of the combined application of chitosan and diosgenin on a mouse skin wound model. For the purpose, wounds (6 mm diameter) were made on mice's backs and were treated for 9 days with one of the following: 50% ethanol (control), polyethylene glycol (PEG) in 50% ethanol, chitosan and PEG in 50% ethanol (Chs), diosgenin and PEG in 50% ethanol (Dg) and chitosan, diosgenin and PEG in 50% ethanol (ChsDg). Before the first treatment and on the 3rd, 6th and 9th days, the wounds were photographed and their area was determined. On the 9th day, animals were euthanized and wounds' tissues were excised for histological analysis. In addition, the lipid peroxidation (LPO), protein oxidation (POx) and total glutathione (tGSH) levels were measured. The results showed that ChsDg had the most pronounced overall effect on wound area reduction, followed by Chs and PEG. Moreover, the application of ChsDg maintained high levels of tGSH in wound tissues, compared to other substances. It was shown that all tested substances, except ethanol, reduced POx comparable to intact skin levels. Therefore, the combined application of chitosan and diosgenin is a very promising and effective medication for wound healing.

The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further development. Here, we present the aroylhydrazone compounds ( 3a and 3b ) regarding their: (i) acute and subacute toxicity in mice; (ii) redox-modulating in vivo and in vitro capacity; (iii) pathomorphology in the liver, kidney, and small intestine tissue specimens; and (iv) intestinal permeability. The acute toxicity test showed that the two investigated compounds exhibited low toxicity by oral and intraperitoneal administration. Changes in behavior, food amount, and water intake were not observed during 14 days of the oral administration at two doses of 1/10 and 1/20 of the LD 50 . The histological examination of the different tissue specimens did not show toxic changes. The in vitro antioxidant assays confirmed the ex vivo results. High gastrointestinal tract permeability at all tested pH values were demonstrated for both compounds. To conclude, both compounds 3a and 3b are highly permeable with low toxicity and can be considered for further evaluation and/or lead optimization.

Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma potential of erufosine is diminished by TWIST1 expression and micellar curcumin substantially increases its antineoplastic activity. Pharmacokinetic analysis showed that the micellar curcumin (MCRM) used in our study was characterized by low zeta potential, slow release of curcumin, and fast cell membrane penetration. The combination ratio 1:4 [erufosine:MCRM] achieved strong synergism by inhibiting cell proliferation and clonogenicity. The combined antiproliferative effects were calculated using the symbolic mathematical software MAPLE 15. The synergistic combination strongly decreased the expression of TWIST1 and protein kinase B/Akt as proven by western blotting. Significant reductions in NF-κB activation, induction of apoptosis, and altered glutathione levels were demonstrated by corresponding assays. In addition, the synergistic combination enhanced the anti-staphylococcal activity and prevented biofilm formation, as shown by crystal violet staining. Taken together, the above results show that the development of nanotechnological treatment modalities for CTCL, based on rational drug combinations exhibiting parallel antineoplastic and antibacterial effects, may prove efficacious.

This study evaluated the in vitro antineoplastic and antiviral potential and in vivo toxicity of twelve extracts with different polarity obtained from the herbaceous perennial plant Geum urbanum L. ( Rosaceae ). In vitro cytotoxicity was determined by ISO 10993-5/2009 on bladder cancer, (T-24 and BC-3C), liver carcinoma (HEP-G2) and normal embryonic kidney (HEK-293) cell lines. The antineoplastic activity was elucidated through assays of cell clonogenicity, apoptosis induction, nuclear factor kappa B p65 (NFκB p65) activation and total glutathione levels. Neutral red uptake study was applied for antiviral activity. The most promising G. urbanum extract was analyzed by UHPLC-HRMS. The acute in vivo toxicity analysis was carried out following OEDC 423. The ethyl acetate extract of aerial parts (EtOAc-AP) exhibited the strongest antineoplastic activity on bladder cancer cell lines (IC 50 = 21.33-25.28 µg/mL) by inducing apoptosis and inhibiting NFκB p65 and cell clonogenicity. EtOAc and n -butanol extracts showed moderate antiviral activity against human adenovirus type 5 and human simplex virus type I. Seventy four secondary metabolites (gallic and ellagic acid derivatives, phenolic acids, flavonoids, etc.) were identified in EtOAc-AP by UHPLC-HRMS. This extract induced no signs of acute toxicity in liver and kidney specimens of H-albino mice in doses up to 210 mg/kg. In conclusion, our study contributes substantially to the detailed pharmacological characterization of G. urbanum , thus helping the development of health-promoting phytopreparations.

A new type aporphine-benzylisoquinoline alkaloid leptofumarine ( 1 ) was isolated from Leptopyrum fumarioides L. The structure of 1 was elucidated based on spectroscopic evidence. Leptofumarine together with the previously isolated leptopyrine ( 2 ) were evaluated for their effect on macrophages and bone marrow (BM) cells in vitro . Both alkaloids inhibited cytokine production by LPS-stimulated peritoneal macrophages. Leptopyrine suppressed osteoclast and osteoblast formation, while leptofumarine affected only osteoblastogenesis.