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Topic Review
Climacostol Analogue as a Prodrug
Drug delivery systems based on pH have emerged as useful carriers for many drugs, including anti-tumor compounds, and are related to the acidic extracellular microenvironment in damaged tissues and some acidic organelles like lysosome and endosome. Here we report on the cytotoxic properties of MOMO, a synthetic precursor of the protozoan antimicrobial and anticancer agent climacostol, which is efficiently activated in mild extracellular acidosis to obtain a great quantity of climacostol in biologically active (Z)-configuration. Biological effects observed on free-living ciliates, tumour cell lines, and Drosophila melanogaster demonstrated that MOMO is well-tolerated in a physiological environment, while its cytotoxicity is rapidly and efficiently triggered at pH 6.3. In addition, the cytostatic versus cytotoxic effects of acidified-MOMO can be modulated in a dose-dependent manner. While these results demonstrate the pH-dependence of MOMO effects, methoxymethyl ether (MOM) protection emerges as a potential prodrug strategy for the design of new efficient pH-sensitive molecules as pharmacologically cytotoxic compounds.
  • 915
  • 28 Oct 2020
Topic Review
Pathogens Associated with Pre-Eclampsia
Pre-eclampsia, the second most frequent direct source of maternal mortality, is a multisystem gestational disorder characterized by proteinuria and maternal hypertension after the 20th gestational week. Metabolic conditions, immunological changes, and fluctuating hormone levels of the pregnant woman induce a dysbiosis of the oral microbiota and contribute to increase inflammation of periodontal tissues. Periodontal pathogens, as well as inflammatory molecules produced in response to periodontopathogens, could diffuse through the bloodstream inducing a placenta inflammatory response. In addition, periodontopathogens can colonize the vaginal microbiota through the gastrointestinal tract or during oro-genital contact. A cumulative bi-directional relationship between periodontal conditions, pathogens and pre-eclampsia exists.
  • 913
  • 24 Nov 2021
Topic Review
Gut Microbiota and Immunotherapy
Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis.
  • 913
  • 26 Aug 2022
Topic Review
Lipid Droplets in Yeast during Stress and Aging
The baker’s yeast Saccharomyces cerevisiae is a valuable tool for aging research, as many aging- and disease-associated pathways such as DNA repair mechanisms, lipostasis, proteostasis, oxidative stress responses, regulated cell death, nutrient signaling, autophagy, and regulation of the cell cycle are evolutionarily conserved to a high degree. Lipid droplets (LDs) are evolutionary conserved structures that were mentioned for the first time by Van Leeuwenhoek in 1674, but their reassessment as autonomous organelles with important key roles in lipid and energy metabolism occurred many years later. LDs originate from the endoplasmic reticulum (ER). In the first step, neutral lipids are synthesized at the ER and are redirected into the bilayer, leading to an aggregation of the highly motile lipids. Emerging evidence suggests that LDs also fulfil impotant functions during aging and in protein homeostasis.
  • 910
  • 12 Oct 2023
Topic Review
Superoxide Dismutases
Several enzymes exist that can convert or degrade reactive oxygen species (ROS); among them are the superoxide dismutases (SODs). SODs are responsible for converting superoxide anions to hydrogen peroxide by dismutation, therefore participating in the ROS detoxification. Here a short overview on the role of SODs in development and pathogenicity of fungi like Podospora anserina and Aspergillus spp. is given. 
  • 909
  • 06 Feb 2022
Topic Review
The Female Reproductive Tract Microbiota
Many intrinsic and extrinsic factors influences the female reproductive tract microbiota (FRTM) that directly affects the reproductive health. It is believed that FRTM dominated by Lactobacilli may play an essential role in obstetric health beyond the woman’s intimate comfort and well-being. Women with altered microbiota may face numerous health-related issues. Altered microbiota can be manipulated and restored to their original shape to re-establish normal reproductive health. 
  • 909
  • 08 Jun 2023
Topic Review
Dynamics of Microbial Plaque Formation on Dentures
Whichever polymer is used in the composition of the prosthetic base (poly methyl methacrylate acrylic (PMMA), polyamide (PA), or polyether ether ketone (PEEK)), the simple presence of a removable prosthesis in the oral cavity can disturb the balance of the oral microbiota. This phenomenon is aggravated by poor oral hygiene, resulting in an increased microbial load coupled with the reduced salivation that is associated with older patients. In 15–70% of patients, this imbalance leads to the appearance of inflammation under the prosthesis (denture stomatitis, DS). DS is dependent on the equilibrium—as well as on the reciprocal, fragile, and constantly dynamic conditions—between the host and the microbiome in the oral cavity. Several local and general parameters contribute to this balance. Locally, the formation of microbial plaque on dentures (DMP) depends on the phenomena of adhesion, aggregation, and accumulation of microorganisms. To limit DMP, apart from oral and lifestyle hygiene, the prosthesis must be polished and regularly immersed in a disinfectant bath. It can also be covered with an insulating coating. In the long term, relining and maintenance of the prosthesis must also be established to control microbial proliferation. On the other hand, several general conditions specific to the host (aging; heredity; allergies; diseases such as diabetes mellitus or cardiovascular, respiratory, or digestive diseases; and immunodeficiencies) can make the management of DS difficult.
  • 906
  • 09 Jan 2024
Topic Review
Mycobacterial Adhesion
Adhesion is crucial for the infective lifestyles of bacterial pathogens. Adhesion to non-living surfaces, other microbial cells, and components of the biofilm extracellular matrix are crucial for biofilm formation and integrity, plus adherence to host factors constitutes a first step leading to an infection. Adhesion is, therefore, at the core of pathogens’ ability to contaminate, transmit, establish residency within a host, and cause an infection. Several mycobacterial species cause diseases in humans and animals with diverse clinical manifestations. Mycobacterium tuberculosis, which enters through the respiratory tract, first adheres to alveolar macrophages and epithelial cells leading up to transmigration across the alveolar epithelium and containment within granulomas. Later, when dissemination occurs, the bacilli need to adhere to extracellular matrix components to infect extrapulmonary sites. Mycobacteria causing zoonotic infections and emerging nontuberculous mycobacterial pathogens follow divergent routes of infection that probably require adapted adhesion mechanisms. New evidence also points to the occurrence of mycobacterial biofilms during infection, emphasizing a need to better understand the adhesive factors required for their formation. 
  • 905
  • 10 Mar 2022
Topic Review
Resident Microbiota and Misfolded Proteins
Neurodegenerative pathologies are commonly characterized by the misfolding, oligomerization and accumulation of toxic species such as Aβ in AD, α-Syn in PD, and the prion protein in CJD. In addition, it appears that a major source of pro-inflammatory diffusible signals associated with brain neuroinflammation originates from peripheral organs and systems such as the gastrointestinal (GI) tract microbiome. Bacterial components such as LPS, which can enter the bloodstream, stimulate systemic pro-inflammatory responses in the host including the CNS. At the cellular and molecular levels, LPS is able to induce the release of inflammatory mediators and eventually induce synaptic loss, which can lead to cognitive impairment via microglial activation, generation of reactive oxygen species (ROS) and oxidative stres. Finally, it appears that signals released by bacteria can modulate amyloid formation and activate pro-inflammatory responses in the brain, suggesting a strong interplay between the microbiome and neuroinflammation in neurodegenerative diseases initiation and progression.  
  • 903
  • 26 Dec 2020
Topic Review
Antimicrobial Mediterranean Wild Edible Plants
Mediterranean wild edible plants (MWEPs) and their antimicrobial properties have been known from ancient times, and nowadays, a growing number of people have rediscovered them as natural remedies for common infections. One of the problems concerning their use is the heterogeneity of the protocols used to extract and analyze the properties of their active principles; such heterogeneity still marks the overall set of scientific studies on MWEPs, not to mention the enormous heterogeneity that characterizes the properties of plants at the outset. We reviewed the current literature on medicinal value of Mediterranean native edible plants trying to emphasize both the weaknesses and the opportunities of these plants. The majority of the reviewed MWEPs can inhibit both Gram-negative and Gram-positive bacteria, and fungi.
  • 903
  • 24 Nov 2021
Topic Review
Study of Water Safety Plan
The use of Microfiltered Water Dispensers (MWDs) is increasing in offices, companies, or commercial facilities, as a response to plastic pollution. Despite their widespread use, poor data are available about the water quality and pathogens developed. Starting from a high contamination found in MWDs, a Water Safety Plan (WSP) was implemented on 57 MWDs to improve the water quality. To assess the effectiveness of WSP during the period 2017–2021, the environmental monitoring of heterotrophic plate counts (HPCs) at 36 °C and 22 °C, Enterococcus spp., Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Clostridium perfringens, as prescribed by Italian regulation for drinking water, was conducted.
  • 901
  • 08 Feb 2022
Topic Review
Borrelia burgdorferi in Ixodidae Tick around Asia
Lyme disease (LD) is a common arthropod-borne inflammatory disorder prevalent in the northern hemisphere. LD is caused by a spirochete named Borrelia burgdorferi s.l., which is transmitted to humans by ticks. Climate, environment, and other factors affect land use; recreational-behavior changes affect human contact with infected ticks. Ixodes, Haemaphysalis and Dermacentor may be the most common tike of B. burgdorferi-positive in Asia. 
  • 901
  • 13 Apr 2022
Topic Review
Drug Resistance in Nontuberculous Mycobacteria
The genus Mycobacterium comprises a multitude of species known to cause serious disease in humans, including Mycobacterium tuberculosis and M. leprae, the responsible agents for tuberculosis and leprosy, respectively. In addition, there is a worldwide spike in the number of infections caused by a mixed group of species such as the M. avium, M. abscessus and M. ulcerans complexes, collectively called nontuberculous mycobacteria (NTMs). The situation is forecasted to worsen because, like tuberculosis, NTMs either naturally possess or are developing high resistance against conventional antibiotics.
  • 900
  • 27 Feb 2021
Topic Review
Extraction from Cyanidium caldarium
Phycocyanin is a blue colored pigment, synthesized by several species of cyanobacteria and red algae. Besides the application as a food-colorant, the pigmented protein is of high interest as a pharmaceutically and nutritionally valuable compound. Since cyanobacteria-derived phycocyanin is thermolabile, red algae that are adapted to high temperatures are an interesting source for phycocyanin extraction. 
  • 898
  • 14 Jul 2021
Topic Review
Sulcia Muelleri
"Candidatus Sulcia muelleri" is an aerobic, gram-negative, bacillus bacteria that is a part of the phylum Bacteroidetes. S. muelleri is an obligate and mutualistic symbiotic microbe commonly found occupying specialized cell compartments of sap-feeding insects called bacteriocytes. A majority of the research done on S. muelleri has detailed its relationship with the host Homalodisca vitripennis. Other studies have documented the nature of its residency in other insects like the maize leafhopper (Cicadulina) or the spittlebug (Cercopoidea). Sulcia muelleri is noted for its exceptionally minimal genome and it is currently identified as having the smallest known sequenced Bacteroidetes genome at only 245 kilobases.
  • 898
  • 20 Oct 2022
Topic Review
Oral Cavity and Candida albicans
Candida colonisation of the oral cavity increases in immunocompromised individuals which leads to the development of oral candidiasis. In addition, host factors such as xerostomia, smoking, oral prostheses, dental caries, diabetes and cancer treatment accelerate the disease process. Candida albicans is the primary causative agent of this infection, owing to its ability to form biofilm and hyphae and to produce hydrolytic enzymes and candialysin. 
  • 897
  • 08 Apr 2022
Topic Review
Aging of Podospora anserina
Podospora anserina is a filamentous fungus that, in contrast to most other fungi, is characterized by a defined limited lifespan. Already in the 1950s it was reported that this ascomycete develops a well-defined senescence syndrome. Depending on the strain, this syndrome occurs after a defined short period of growth (e.g., after 2–3 weeks): the pigmentation of the peripheral part of the thallus increases while the growth rate decreases until it comes to a complete stop and the thallus dies at the growth front. The molecular basis of aging of P. anserina have been carefully investigated over more than 60 years of research and a network of pathways and their interactions have been uncovered.
  • 894
  • 22 Apr 2021
Topic Review
Propolis on Infectious Diseases
Infectious diseases are a significant problem affecting the public health and economic sta‐ bility of societies all over the world. Treatment is available for most of these diseases; however, many pathogens have developed resistance to drugs, necessitating the development of new thera‐ pies with chemical agents, which can have serious side effects and high toxicity. In addition, the severity and aggressiveness of emerging and re‐emerging diseases, such as pandemics caused by viral agents, have led to the priority of investigating new therapies to complement the treatment of different infectious diseases. Alternative and complementary medicine is widely used throughout the world due to its low cost and easy access and has been shown to provide a wide repertoire of options for the treatment of various conditions. In this work, we address the relevance of the effects of propolis on the causal pathogens of the main infectious diseases with medical relevance; the ex‐ isting compiled information shows that propolis has effects on Gram‐positive and Gram‐negative bacteria, fungi, protozoan parasites and helminths, and viruses; however, challenges remain, such as the assessment of their effects in clinical studies for adequate and safe use.
  • 894
  • 08 Jun 2021
Topic Review
HERV-K, Immune Response in ALS
Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.
  • 890
  • 31 Aug 2021
Topic Review
Cas12-Based CRISPR-Dx
Based on the current development in the field of diagnostics, the programmable clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system appears to be a promising technology that can be further explored to create rapid, cost-effective, sensitive, and specific diagnostic tools for both laboratory and point-of-care (POC) testing.
  • 887
  • 20 Dec 2021
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