Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease

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Highlights

• •MS-based clinical assay that accurately determines phospho Rab10 occupancy.
• •Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
• •Determination of pRab levels in neutrophils of Parkinson disease patients.
• •Relevance of pRab levels as marker of PD.

     

Metabolic defects shared by Alzheimer's disease and diabetes: A focus on mitochondria

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two global epidemics that share several metabolic defects, such as insulin resistance, impaired glucose metabolism, and mitochondrial defects. Importantly, strong evidence demonstrates that T2D significantly increases the risk of cognitive decline and dementia, particularly AD. Here, we provide an overview of the metabolic defects that characterize and link both pathologies putting the focus on mitochondria. The biomarker potential of mitochondrial components and the therapeutic potential of some drugs that target and modulate mitochondria are also briefly discussed.     

Antimicrobial effect of different herbal plant extracts against different microbial population

This study evaluates the antimicrobial effects of ethanolic extract of five herbal plants; Guava (Psidium guajava), Sage (Salvia officinalis), Rhamnus (Ziziphusspina Christi), Mulberry (Morusalba L.), and Olive (Oleaeuropaea L) leaves against several microbial population representing Gram positive, Gram negative and Mollicutes; S. aureus, E. coli, Pasteurella multocida, B. cereus, Salmonella Enteritidis and M. gallisepticum using standard agar disc diffusion technique and minimal inhibitory concentration (MIC). Different extracts reveal variable results against the microorganism under study. All extracts have no antibacterial potency for Mycoplasma gallisepticum except Psidium guajava. The results of minimal inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) of the extracts against the six bacteria ranged from 625 to 5000 μg/ml. The used herbal extract could inhibit the selected microorganism under study with variable minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC).     

Biology of brain metastases and novel targeted therapies: Time to translate the research

Brain metastases (BM) occur in 20% to 40% of patients with cancer and result in significant morbidity and poor survival. The main therapeutic options include surgery, whole brain radiotherapy, stereotactic radiosurgery and chemotherapy. Although significant progress has been made in diagnostic and therapeutic methods, the prognosis in these patients remains poor. Furthermore, the poor penetrability of chemotherapy agents through the blood brain barrier (BBB) continues to pose a challenge in the management of this disease. Preclinical evidence suggests that new targeted treatments can improve local tumor control but our clinical experience with these agents remains limited. In addition, several clinical studies with these novel agents have produced disappointing results. This review will examine the knowledge of targeted therapies in BM. The preclinical and clinical evidence of their use in BM induced by breast cancer, non-small cell lung cancer and melanoma will be presented. In addition, we will discuss the role of antiangiogenic and radiosensitising agents in the treatment of BM and the current strategies available to increase BBB permeability. A better understanding of the mechanism of action of these agents will help us to identify the best targets for testing in future clinical studies.     

Alternative approach to species identification of Actaea racemosa L. (syn. Cimicifuga racemosa (L.) Nutt., black cohosh) herbal starting material: UV spectroscopy coupled with LDA

The North American Actaea racemosa L. (syn. Cimicifuga racemosa (L.) Nutt., commonly known as black cohosh), considered to be a more “natural” alternative to conventional therapies, is used to relieve menopausal symptoms. The high demand for plant material has led to problems with substitution/adulteration of raw material of wholesale origin. The authenticity of the starting material is crucial for the herbal product’s efficacy and safety, and tests on identity and substitution are integral parts of cGMP guidelines. Consequently, there is a need for economical and easy-applicable test procedures. The aim of this study is to reveal the capability of the well-established UV spectroscopy coupled with a multivariate classification procedure to serve as a tool for the identification of A. racemosa. We built a classification model applying linear discriminant analysis (LDA) to distinguish between A. racemosa and its common substitutes. The model showed a high level of accuracy predicting 100% of the samples correctly. Our results indicate that UV spectroscopy shows potential for the development of possible additional authentication methods for this herbal starting material.     

T-cell therapies for T-cell lymphoma

T-cell lymphomas represent a subpopulation of non-Hodgkin lymphomas with poor outcomes when treated with conventional chemotherapy. A variety of novel agents have been introduced as new treatment strategies either as first-line treatment or in conjunction with chemotherapy. Immunotherapy has been demonstrated to be a promising area for new therapeutics, including monoclonal antibodies and adoptive cellular therapeutics. T-cell therapeutics have been shown to have significant success in the treatment of B-cell malignancies and are rapidly expanding as potential treatment options for other cancers including T-cell lymphomas. Although treating T-cell lymphomas with T-cell therapeutics has unique challenges, multiple targets are currently being studied both preclinically and in clinical trials.     

SHP2 Drives Adaptive Resistance to ERK Signaling Inhibition in Molecularly Defined Subsets of ERK-Dependent Tumors

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Flavoring and extending the shelf life of cucumber juice with aroma compounds-rich herbal extracts at 4 °C through controlling chemical and microbial fluctuations

This work aims to enhance the flavor of functional cucumber juice using herbal extracts of peppermint, basil, lavender, and lemongrass ethanolic extracts and extend its lifetime by controlling the chemical and microbial fluctuations. Cucumber juices were processed as; non-supplemented (J-Con), J-PME, J-BE, J-LE, and J-LEE supplemented with peppermint, basil, lavender, and lemongrass ethanolic extracts, respectively. Peppermint extract was significantly scavenged 88% of DPPH radicals and inhibited the growth of tested gram-positive, gram-negative bacteria and fungi followed by the lemongrass extract. The antioxidant activity of cucumber juices increased due to polyphenols and aroma compounds in the added extracts. However, the antioxidant content was decreased after two months of storage at 4 °C, due to the decrease in polyphenols. The flavor compounds were determined using GC mass, wherein hydrocarbons, acids, alcohols, and carbonyl compounds were the main aroma contents in cucumber juices, and their contents decreased with storage time. Peppermint and lemongrass extracts were significantly (p ≤ 0.05) increased the whiteness of J-PME, and J-LEE, respectively. The highest score of flavor and taste was observed in J-PME that scored 8.3 based on panelists'' reports followed by J-LEE. The PME was significantly maintained 91% of the odor and color of J-PME as compared to other juices.