Factors Determining the Susceptibility of Bacteria to Antibacterial Photodynamic Inactivation

Photodynamic inactivation of microorganisms (aPDI) is an excellent method to destroy antibiotic-resistant microbial isolates. The use of an exogenous photosensitizer or irradiation of microbial cells already equipped with endogenous photosensitizers makes aPDI a convenient tool for treating the infections whenever technical light delivery is possible. Currently, aPDI research carried out on a vast repertoire of depending on the photosensitizer used, the target microorganism, and the light delivery system shows efficacy mostly on in vitro models. The search for mechanisms underlying different responses to photodynamic inactivation of microorganisms is an essential issue in aPDI because one niche (e.g., infection site in a human body) may have bacterial subpopulations that will exhibit different susceptibility. Rapidly growing bacteria are probably more susceptible to aPDI than persister cells. Some subpopulations can produce more antioxidant enzymes or have better performance due to efficient efflux pumps. The ultimate goal was and still is to identify and characterize molecular features that drive the efficacy of antimicrobial photodynamic inactivation. To this end, we examined several genetic and biochemical characteristics, including the presence of individual genetic elements, protein activity, cell membrane content and its physical properties, the localization of the photosensitizer, with the result that some of them are important and others do not appear to play a crucial role in the process of aPDI. In the review, we would like to provide an overview of the factors studied so far in our group and others that contributed to the aPDI process at the cellular level. We want to challenge the question, is there a general pattern of molecular characterization of aPDI effectiveness? Or is it more likely that a photosensitizer-specific pattern of molecular characteristics of aPDI efficacy will occur?

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Isolation and characterization of Pseudomonas syringae isolates affecting stone fruits and almond in Montenegro

Journal of Plant Diseases and Protection ◽

10.1007/s41348-020-00417-8 ◽

2021 ◽

Author(s):

Tamara Popović ◽

Jelena Menković ◽

Anđelka Prokić ◽

Nevena Zlatković ◽

Aleksa Obradović

Keyword(s):

Pseudomonas Syringae ◽

Housekeeping Genes ◽

Molecular Characteristics ◽

Biochemical Tests ◽

High Genetic Diversity ◽

Leaf Petiole ◽

Molecular Features ◽

Isolation And Characterization ◽

Genomic Species

AbstractIn Montenegro, stone fruit species are grown on intensive and semi-intensive commercial plantations. However, almond production is mainly organized on family gardens and for household consumption. During two seasons (2017–2018), we surveyed apricot, peach, nectarine, sweet cherry, Japanese plum, and almond orchards for the presence of bacterial diseases at different geographical locations in Montenegro. From leaf, petiole and fruit lesions, branch or twig cankers, and necrotizing buds, a total of 29 isolates were obtained and subjected to identification based on their morphological, pathogenic, biochemical, and molecular characteristics. Pathogenicity of the isolates was confirmed by reproducing the symptoms on leaves, fruits, and twigs of the corresponding host plants. The biochemical tests indicated that the isolates belong to Pseudomonas syringae. However, isolates’ characterization showed variation in their phenotypic and molecular features. The presence of the syrB gene and ice nucleation activity grouped most of the isolates within pathovar syringae. The results of rep-PCR using the BOX primer revealed high genetic diversity of isolates. Multilocus sequence analysis (MLSA), using four housekeeping genes, showed that 27 isolates belong to the genomic species 1, P. syringae sensu stricto, corresponding to P. syringae phylogroup 2. However, isolates from the same phylogroup 2 did not form a monophyletic group. One strain isolated from apricot was most distinct and similar to members of genomic species 2, phylogroup 3. All tested isolates showed significant levels of resistance to copper sulfate and high level of sensitivity to streptomycin sulfate in vitro.

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Clinical, Hematologic, Biologic and Molecular Characteristics of Patients with Myeloproliferative Neoplasms and a Chronic Myelomonocytic Leukemia-Like Phenotype

Cancers ◽

10.3390/cancers12071891 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1891

Author(s):

Sonja Heibl ◽

Bettina Gisslinger ◽

Eva Jäger ◽

Agnes Barna ◽

Michael Gurbisz ◽

...

Keyword(s):

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Jak2 V617f ◽

Primary Myelofibrosis ◽

Chronic Myelomonocytic Leukemia ◽

Molecular Characteristics ◽

Molecular Features ◽

Cell Counts ◽

Myelomonocytic Leukemia

Patients with a myeloproliferative neoplasm (MPN) sometimes show a chronic myelomonocytic leukemia (CMML)-like phenotype but, according to the 2016 WHO classification, a documented history of an MPN excludes the diagnosis of CMML. Forty-one patients with an MPN (35 polycythemia vera (PV), 5 primary myelofibrosis, 1 essential thrombocythemia) and a CMML-like phenotype (MPN/CMML) were comprehensively characterized regarding clinical, hematologic, biologic and molecular features. The white blood cell counts in MPN/CMML patients were not different from CMML patients and PV patients. The hemoglobin values and platelet counts of these patients were higher than in CMML but lower than in PV, respectively. MPN/CMML patients showed myelomonocytic skewing, a typical in vitro feature of CMML but not of PV. The mutational landscape of MPN/CMML was not different from JAK2-mutated CMML. In two MPN/CMML patients, development of a CMML-like phenotype was associated with a decrease in the JAK2 V617F allelic burden. Finally, the prognosis of MPN/CMML (median overall survival (OS) 27 months) was more similar to CMML (JAK2-mutated, 28 months; JAK2-nonmutated 29 months) than to PV (186 months). In conclusion, we show that patients with MPN and a CMML-like phenotype share more characteristics with CMML than with PV, which may be relevant for their classification and clinical management.

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Epigenetic Mechanisms of Stem Cell Aging and Rejuvenation

Blood ◽

10.1182/blood.v124.21.sci-44.sci-44 ◽

2014 ◽

Vol 124 (21) ◽

pp. SCI-44-SCI-44

Author(s):

Thomas A. Rando

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Molecular Mechanisms ◽

Conflicts Of Interest ◽

Cell Aging ◽

Molecular Characteristics ◽

Molecular Features ◽

Functional Features

Abstract For most tissues, stem cell numbers decline negligibly with age; nevertheless, there is an age-dependent decline in stem cell functionality. Many molecular, biochemical, and functional features of stem cells have been characterized across a broad range of tissues, and these changes have been assumed to be largely irreversible and inevitable accompaniments of aging. However, in studies both in vivo and in vitro we have demonstrated a reversibility of the functional and, in some cases, molecular characteristics of aged stem cells. Supported by compelling data from studies of heterochronic parabiotic pairings of mice, it is clear that the aged phenotype can be modified when aged cells are exposed to a youthful systemic milieu. These findings challenge the fundamental tenet of aging as an irreversible process and raises the question of whether, or to what extent, the aged phenotype is epigenetically determined. We have begun to examine the epigenetic profiles of young, old, and “rejuvenated” old stem cells to attempt to define youthfulness and aging in epigenetic terms. To the extent that aging can be “reprogrammed” back to youthfulness in somatic tissues, it has parallels to the resetting of the aging clock that occurs with somatic cell nuclear transfer. Elucidating the underlying molecular features, both genetic and epigenetic, of aged stem cells will provide a framework for understanding the fundamental molecular mechanisms of aging and the mechanisms by which environmental influences, such as those that occur in the setting of heterochronic parabiosis, can reverse the mechanisms of aging. Disclosures No relevant conflicts of interest to declare.

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Effects of gamma ray on some molecular characteristics of in vitro regenerated Gerbera jamesonii Bolus

Bangladesh Journal of Botany ◽

10.3329/bjb.v39i2.7490 ◽

1970 ◽

Vol 39 (2) ◽

pp. 207-214

Author(s):

Nazma Akter ◽

RH Sarker ◽

MI Hoque

Keyword(s):

Gamma Ray ◽

Molecular Characteristics ◽

Gerbera Jamesonii

DOI: 10.3329/bjb.v39i2.7490Bangladesh J. Bot. 39(2): 207-214, 2010 (December)

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Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

Current Pharmaceutical Design ◽

10.2174/1381612826666200408101550 ◽

2020 ◽

Vol 26 (22) ◽

pp. 2610-2619 ◽

Cited By ~ 2

Author(s):

Tarique Hussain ◽

Ghulam Murtaza ◽

Huansheng Yang ◽

Muhammad S. Kalhoro ◽

Dildar H. Kalhoro

Keyword(s):

Oxidative Stress ◽

Chronic Diseases ◽

Inflammatory Diseases ◽

Therapeutic Option ◽

Cellular Level ◽

Antiinflammatory Drugs ◽

Suitable Alternative ◽

Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

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Insights on Molecular Characteristics of Hydrochars by 13C-NMR and Off-Line TMAH-GC/MS and Assessment of Their Potential Use as Plant Growth Promoters

Molecules ◽

10.3390/molecules26041026 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1026 ◽

Cited By ~ 1

Author(s):

Laís G. Fregolente ◽

João Vitor dos Santos ◽

Giovanni Vinci ◽

Alessandro Piccolo ◽

Altair B. Moreira ◽

...

Keyword(s):

Plant Growth ◽

Phosphoric Acid ◽

13C Nmr ◽

Chemical Properties ◽

Water Soluble ◽

Molecular Characteristics ◽

Initial Growth ◽

Growth Promoters ◽

Molecular Features ◽

Potential Use

Hydrochar is a carbon-based material that can be used as soil amendment. Since the physical-chemical properties of hydrochar are mainly assigned to process parameters, we aimed at evaluating the organic fraction of different hydrochars through 13C-NMR and off-line TMAH-GC/MS. Four hydrochars produced with sugarcane bagasse, vinasse and sulfuric or phosphoric acids were analyzed to elucidate the main molecular features. Germination and initial growth of maize seedlings were assessed using hydrochar water-soluble fraction to evaluate their potential use as growth promoters. The hydrochars prepared with phosphoric acid showed larger amounts of bioavailable lignin-derived structures. Although no differences were shown about the percentage of maize seeds germination, the hydrochar produced with phosphoric acid promoted a better seedling growth. For this sample, the greatest relative percentage of benzene derivatives and phenolic compounds were associated to hormone-like effects, responsible for stimulating shoot and root elongation. The reactions parameters proved to be determinant for the organic composition of hydrochar, exerting a strict influence on molecular features and plant growth response.

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Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease

Cell Death and Differentiation ◽

10.1038/s41418-020-00685-9 ◽

2021 ◽

Author(s):

Wen-Dai Bao ◽

Pei Pang ◽

Xiao-Ting Zhou ◽

Fan Hu ◽

Wan Xiong ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Impairment ◽

Iron Homeostasis ◽

Critical Role ◽

Gene Set Enrichment Analysis ◽

Molecular Characteristics ◽

Intracellular Iron

AbstractIron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

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Investigation of Chlorella pyrenoidosa Protein as a Source of Novel Angiotensin I-Converting Enzyme (ACE) and Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides

Nutrients ◽

10.3390/nu13051624 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1624

Author(s):

Yuchen Li ◽

Gilda Aiello ◽

Enrico Mario Alessandro Fassi ◽

Giovanna Boschin ◽

Martina Bartolomei ◽

...

Keyword(s):

Chlorella Pyrenoidosa ◽

Cellular Level ◽

Potential Interaction ◽

Converting Enzyme ◽

Inhibitory Peptides ◽

Angiotensin I Converting Enzyme ◽

Dpp Iv ◽

Ace Activity ◽

The Stability

Chlorella pyrenoidosa (C. pyrenoidosa) is a microalgae species with a remarkably high protein content that may potentially become a source of hypotensive and hypoglycemic peptides. In this study, C. pyrenoidosa proteins were extracted and hydrolyzed overnight with pepsin and trypsin with final degrees of hydrolysis of 18.7% and 35.5%, respectively. By LC-MS/MS, 47 valid peptides were identified in the peptic hydrolysate (CP) and 66 in the tryptic one (CT). At the concentration of 1.0 mg/mL, CP and CT hydrolysates inhibit in vitro the angiotensin-converting enzyme (ACE) activity by 84.2 ± 0.37% and 78.6 ± 1.7%, respectively, whereas, tested at cellular level at the concentration of 5.0 mg/mL, they reduce the ACE activity by 61.5 ± 7.7% and 69.9 ± 0.8%, respectively. At the concentration of 5.0 mg/mL, they decrease in vitro the DPP-IV activity by 63.7% and 69.6% and in Caco-2 cells by 38.4% and 42.5%, respectively. Short peptides (≤10 amino acids) were selected for investigating the potential interaction with ACE and DPP-IV by using molecular modeling approaches and four peptides were predicted to block both enzymes. Finally, the stability of these peptides was investigated against gastrointestinal digestion.

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Chromatography-Independent Fractionation and Newly Identified Molecular Features of the Adzuki Bean (Vigna angularis Willd.) β-vignin Protein

International Journal of Molecular Sciences ◽

10.3390/ijms22063018 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3018

Author(s):

Biane Philadelpho ◽

Victória Souza ◽

Fabiani Souza ◽

Johnnie Santos ◽

Fabiana Batista ◽

...

Keyword(s):

Metal Binding ◽

Cardiovascular Health ◽

Binding Capacity ◽

Biological Activities ◽

Electrophoretic Analysis ◽

Adzuki Bean ◽

Molecular Features ◽

Health Promoting ◽

High Degree

Adzuki seed β-vignin, a vicilin-like globulin, has proven to exert various health-promoting biological activities, notably in cardiovascular health. A simple scalable enrichment procedure of this protein for further nutritional and functional studies is crucial. In this study, a simplified chromatography-independent protein fractionation procedure has been optimized and described. The electrophoretic analysis showed a high degree of homogeneity of β-vignin isolate. Furthermore, the molecular features of the purified protein were investigated. The adzuki bean β-vignin was found to have a native size of 146 kDa, and the molecular weight determined was consistent with a trimeric structure. These were identified in two main polypeptide chains (masses of 56–54 kDa) that are glycosylated polypeptides with metal binding capacity, and one minor polypeptide chain with a mass 37 kDa, wherein these features are absent. The in vitro analysis showed a high degree of digestibility of the protein (92%) and potential anti-inflammatory capacity. The results lay the basis not only for further investigation of the health-promoting properties of the adzuki bean β-vignin protein, but also for a possible application as nutraceutical molecule.

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Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer

Cancers ◽

10.3390/cancers13163975 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3975

Author(s):

Marco A. De Velasco ◽

Yurie Kura ◽

Naomi Ando ◽

Noriko Sako ◽

Eri Banno ◽

...

Keyword(s):

Prostate Cancer ◽

Antitumor Activity ◽

Cancer Cells ◽

Late Stage ◽

Early Stage ◽

Castration Resistant Prostate Cancer ◽

Akt Inhibitor ◽

Molecular Features ◽

Context Specific

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.

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