Rational Design of Antifungal Peptides Based on the γ-Core Motif of a () Antifungal Protein to Improve Structural Integrity, Efficacy, and Spectrum.

Antifungal peptides offer promising alternative compounds for the treatment of fungal infections, for which new antifungal compounds are urgently needed. Constant and broad antifungal spectra of these peptides play essential roles in their reliable therapeutic application. It has been observed that rationally designed peptides using the evolutionarily conserved γ-core region (GXC-X-C) of an antifungal protein from () highly inhibit the growth of fungi.

Mechanism of Analgesia by Gabapentinoid Drugs: Involvement of Modulation of Synaptogenesis and Trafficking of Glutamate-Gated Ion Channels.

Gabapentinoids have clinically been used for treating epilepsy, neuropathic pain, and several other neurologic disorders for >30 years; however, the definitive molecular mechanism responsible for their therapeutic actions remained uncertain. The conventional pharmacological observation regarding their efficacy in chronic pain modulation is the weakening of glutamate release at presynaptic terminals in the spinal cord. While the 2/-1 subunit of voltage-gated calcium channels (VGCCs) has been identified as the primary drug receptor for gabapentinoids, the lack of consistent effect of this drug class on VGCC function is indicative of a minor role in regulating this ion channel's activity.

Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2.

As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity.

Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Antifungal Protein, AFP.

Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation.

Examining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study.

Introduction: Transdermal cannabinoids may provide better safety and bioavailability profiles compared with other routes of administration. This single-arm, open-label study investigated a novel topical transdermal delivery system on the pharmacokinetics of cannabidiol (CBD) and tetrahydrocannabinol (THC).

Methods: Participants were 39.

[Pyoderma gangrenosum of the breast – Case report].

Pyoderma gangrenosum (PG) of the breast is a rare, ulcerative disease of rapid onset normally associated with systemic disorders and triggered by surgery or trauma. Early diagnosis and appropriate treatment of this disease pose a real challenge. We present a case of a PG of the breast in a patient with associated diabetes mellitus, with minor triggering injury.

An 80-Year-Old Man with Ischemic Heart Disease Who Developed Thrombotic Thrombocytopenic Purpura Following Treatment with Ticagrelor.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is associated with widespread microvascular thrombosis, low platelet count, and hemolysis. Ticagrelor is a relatively new agent which functions as a reversible inhibitor of the P2Y12 receptor working to prevent platelet aggregation and is used with or without aspirin in patients with acute coronary syndrome to reduce the risk of myocardial infarction and stroke. We describe the case of an 80-year-old man with ischemic heart disease who developed this rare and potentially fatal adverse reaction known as TTP following treatment with ticagrelor.

The Membrane Activity of the Amphibian Temporin B Peptide Analog TB_KKG6K Sheds Light on the Mechanism That Kills Candida albicans.

Temporin B (TB) is a 13-amino-acid-long, cationic peptide secreted by the granular glands of the European frog Rana temporaria. We recently showed that the modified TB peptide analog TB_KKG6K rapidly killed planktonic and sessile Candida albicans at low micromolar concentrations and was neither hemolytic nor cytotoxic to mammalian cells . The present study aimed to shed light into its mechanism of action, with a focus on its fungal cell membrane activity.

Rationally Designed Antimicrobial Peptides Are Potential Tools to Combat Devastating Bacteria and Fungi.

The introduction of the first antibiotic (penicillin) by Sir Alexander Fleming in 1928 was a huge milestone in the treatment of infectious diseases [...

The combination of () antifungal proteins with rationally designed γ-core peptide derivatives is effective for plant and crop protection.

Unlabelled: Plant pathogenic fungi are responsible for enormous crop losses worldwide. Overcoming this problem is challenging as these fungi can be highly resistant to approved chemical fungicides. There is thus a need to develop and introduce fundamentally new plant and crop protection strategies for sustainable agricultural production.

Falsely positive heparin-induced thrombocytopenia antibody testing in severe hyperbilirubinemia.

Heparin-induced thrombocytopenia (HIT) is a life-threatening pathologic reaction to heparin-based products. Diagnosis of this condition can be confounded by other comorbidities or by acute illness-oftentimes presenting challenging clinical dilemmas, particularly in critically ill patients. A 67-year-old woman was admitted with liver failure and severe hyperbilirubinemia.

The neuropathic itch: Don't scratch your head too hard!

Postherpetic complications can sometimes result in significant debility. A multidisciplinary approach is crucial in deciding the appropriate treatment strategy in these patients.

Solution Structure, Dynamics, and New Antifungal Aspects of the Cysteine-Rich Miniprotein PAFC.

The genome of Q176 contains a gene coding for the 88-amino-acid (aa)-long glycine- and cysteine-rich antifungal protein C (PAFC). After maturation, the secreted antifungal miniprotein (MP) comprises 64 aa and shares 80% aa identity with the bubble protein (BP) from , which has a published X-ray structure. Our team expressed isotope (N, C)-labeled, recombinant PAFC in high yields, which allowed us to determine the solution structure and molecular dynamics by nuclear magnetic resonance (NMR) experiments.

The Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Biofilms.

is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti- activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against biofilms.

The Q176 Antimicrobial Protein PAFC Effectively Inhibits the Growth of the Opportunistic Human Pathogen .

Small, cysteine-rich and cationic antimicrobial proteins (AMPs) from filamentous ascomycetes promise treatment alternatives to licensed antifungal drugs. In this study, we characterized the Q176 antifungal protein C (PAFC), which is phylogenetically distinct to the other two antifungal proteins, PAF and PAFB, that are expressed by this biotechnologically important ascomycete. PAFC is secreted into the culture broth and is co-expressed with PAF and PAFB in the exudates of surface cultures.

Secondary Plasma Cell Leukemia: A Case Report.

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma and has a poor prognosis. It needs prompt recognition in order to institute timely treatment. Given its relatively low incidence, it is an evolving area of research as well.

Biofungicidal Potential of () Antifungal Protein NFAP and Novel Synthetic γ-Core Peptides.

Because of enormous crop losses worldwide due to pesticide-resistant plant pathogenic fungi, there is an increasing demand for the development of novel antifungal strategies in agriculture. Antifungal proteins (APs) and peptides are considered potential biofungicides; however, several factors limit their direct agricultural application, such as the high cost of production, narrow antifungal spectrum, and detrimental effects to plant development and human/animal health. This study evaluated the safety of the application of APs and peptides from the ascomycete as crop preservatives.

Predicting response to topical non-steroidal anti-inflammatory drugs in osteoarthritis: an individual patient data meta-analysis of randomized controlled trials.

Objectives: To identify predictors of the specific (difference between treatment and placebo) and overall (change from baseline in treatment arm) treatment effects of topical NSAIDs in OA.

Methods: Randomized controlled trials (RCTs) of topical NSAIDs in OA were identified through systematic literature searching and inquiry to pharmaceutical companies. The raw, de-identified data were analysed in one-stage individual patient data meta-analysis (IPD-MA).

The potential use of the Penicillium chrysogenum antifungal protein PAF, the designed variant PAF and its γ-core peptide Pγ in plant protection.

The prevention of enormous crop losses caused by pesticide-resistant fungi is a serious challenge in agriculture. Application of alternative fungicides, such as antifungal proteins and peptides, provides a promising basis to overcome this problem; however, their direct use in fields suffers limitations, such as high cost of production, low stability, narrow antifungal spectrum and toxicity on plant or mammalian cells. Recently, we demonstrated that a Penicillium chrysogenum-based expression system provides a feasible tool for economic production of P.

Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB.

The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins.

Clinical Advancement and Challenges of Expansion of Human Cord Blood Cells.

Apart from peripheral blood stem cell (PBSC), umbilical cord blood (UCB) is now a recognized source of stem cells for transplantation. UCB is an especially important source of stem cells for minority populations, which would otherwise be unable to find appropriately matched adult donors. UCB has fewer mature T lymphocytes compared with peripheral blood, thus making a UCB transplantation (UCBT) with a greater degree of HLA mismatch possible.

Current Status and Perspectives of Irradiation-Based Conditioning Regimens for Patients with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Acute myeloid leukemia and acute lymphoblastic leukemia are the most common indications for allogeneic hematopoietic stem cell transplantation. Total body irradiation (TBI) is an important part of conditioning regimens. TBI-based regimens offer advantages in sanctuary sites but are associated with significant risks of early and late side effects, including pulmonary toxicity, growth retardation, and second malignancy.

Acute Left Internal Carotid Artery and Right Popliteal Artery Occlusion Related to Cisplatin-Gemcitabine Based Chemotherapy.

Objectives: The increased risk of thromboembolic complications with active cancer is well known. We present this case to highlight that chemotherapy may increase the risk of thromboembolic events even further in cancer patients.

Methods: We report a case of a 64-year-old male with Diffuse Large B-Cell Non-Hodgkin's Lymphoma who presented with left-sided headache and right calf pain two weeks after starting Rituximab/Gemcitabine/Cisplatin/Dexamethasone chemotherapy.