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Parkinson's Disease is a highly complicated neurological disorder, with a key manifestation of loss of dopaminergic neurons. Despite the plethora of medicines that alleviate the symptoms, there is an urgent need for new treatments acting on the fundamental pathology of PD. Non-coding RNAs are becoming increasingly important in gene regulation and various cellular processes and are found to play a role in PD pathophysiology. This review analyzes the cross-talk of distinct ncRNAs with dopamine signaling. We attempt to constrain the various ncRNA networks that can activate dopamine production. First, we describe the deregulation of miRNAs that target dopamine receptors and have been implicated in PD. Next, we turn to the functions of lncRNAs in dopaminergic neurons and the connections to susceptibility genes for PD. Finally, we will analyze the novel circRNAs, such as ciRS-7, which may modulate dopamine-linked processes and serve as possible PD biomarkers. In this review, we describe recent progress in dopamine neuron revival to treat PD and the therapeutic potential of ncRNA. This review critically evaluates the available data, and we predict the role of some ncRNAs, such as PTBP1, to become candidate treatment targets in the future. Thus, this review aims to summarize the molecular causes for the deficit in dopamine signaling in PD and point to novel ncRNAs-linked therapeutic directions in neuroscience., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

We describe the genome of a lytic phage EKq1 isolated on Klebsiella quasipneumoniae , with activity against Klebsiella pneumoniae . EKq1 is an unclassified representative of the class Caudoviricetes, similar to Klebsiella phages VLCpiS8c, phiKp_7-2, and vB_KleS-HSE3. The 48,244-bp genome has a GC content of 56.43% and 63 predicted protein-coding genes., Competing Interests: The authors declare no conflict of interest.

We describe the genome of a lytic phage EAb13 isolated from sewage, with broad activity against multidrug-resistant Acinetobacter baumannii . EAb13 is an unclassified siphovirus. Its genome consists of 82,411 bp, with 40.15% GC content, 126 protein-coding sequences, 1 tRNA, and 2,177 bp-long direct terminal repeats., Competing Interests: The authors declare no conflict of interest.

Bambusae caulis in Liquamen (BCL), which is extracted from heat-treated fresh bamboo stems, is a traditional herbal medicine widely used in Eastern countries. Recently, it has been reported to have anti-inflammatory and whitening effects. However, the protective effect of BCL on hepatocytes has not yet been elucidated. The present study aimed to determine whether BCL prevents oxidative stress induced by tert-butyl hydroperoxide (t-BHP) and exerts cytoprotective effects on hepatocytes. High-performance liquid chromatography and liquid chromatography with tandem mass spectroscopy were performed to analyze the type of polyphenols present in BCL. The activities of antioxidant enzymes and hepatocyte viability were assessed. The benzoic acid content was the highest among polyphenols present in BCL. Benzoic acid acts as a scavenger of free radicals, including reactive oxygen species. BCL increased the expression of antioxidant enzymes (glutamate-cysteine ligase and NADPH quinone dehydrogenase (1)) by activating nuclear factor erythroid 2-related factor 2 and reduced tBHP-induced cell death by inhibiting oxidative stress. BCL inhibited tBHP-induced phosphorylation of p38 and c-Jun N-terminal kinase but not that of extracellular signal-regulated kinase. In conclusion, BCL is a promising therapeutic candidate for treating oxidative-stress-induced hepatocyte damage.

Nearly 35 million people worldwide live with Alzheimer's disease (AD). The prevalence of the disease is expected to rise two-fold by 2050. With only symptomatic treatment options available, it is essential to understand the developments and existing evidence that aims to target brain pathology and dementia outcomes. This scoping systematic review aimed to collate existing evidence of CT1812 for use in patients with AD and summarize the methodologies of ongoing trials. Adhering to PRISMA Statement 2020 guidelines, PubMed/MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were systematically searched through up to 15 November 2022 by applying the following keywords: CT1812, Alzheimer's disease, dementia, and/or sigma-2 receptor. Three completed clinical trials were included along with three ongoing records of clinical trials. The three completed trials were in Phases I and II of testing. The sample size across all three trials was 135. CT1812 reached endpoints across the trials and obtained a maximum concentration in the cerebrospinal fluid with 97-98% receptor occupancy. The findings of this systematic review must be used with caution as the results, while mostly favorable so far, must be replicated in higher-powered, placebo-controlled Phase II-III trials., Competing Interests: The authors declare no conflict of interest.

The authorization for emergency use of a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been issued in diverse countries in December 2020, and additional vaccine candidates soon may be cleared for a similar emergency use. If it is reasonable to believe that in some Western countries most people may be vaccinated by the end of 2021, insufficient supplies, access inequities across countries, and deficiencies in enforcing the participatory engagement of communities will present important challenges for the achievement of sufficient vaccination coverage worldwide in less than 2-3 years. A possible strategy for bridging the gap until full vaccine deployment is based on the integration of improved non-pharmaceutical measures and recently authorized pharmaceutical interventions to reduce as much as possible hospitalizations and deaths in the coming months, when recurring infection peaks are expected.

The objective of this study was to characterize the enzymatic hydrolysis of lipopolysaccharide (LPS) by wheat phytase and to investigate the effects of wheat phytase-treated LPS on in vitro toxicity, cell viability and release of a pro-inflammatory cytokine, interleukin (IL)-8 by target cells compared with the intact LPS. The phosphatase activity of wheat phytase towards LPS was investigated in the presence or absence of inhibitors such as L-phenylalanine and L-homoarginine. In vitro toxicity of LPS hydrolyzed with wheat phytase in comparison to intact LPS was assessed. Cell viability in human aortic endothelial (HAE) cells exposed to LPS treated with wheat phytase in comparison to intact LPS was measured. The release of IL-8 in human intestinal epithelial cell line, HT-29 cells applied to LPS treated with wheat phytase in comparison to intact LPS was assayed. Wheat phytase hydrolyzed LPS, resulting in a significant release of inorganic phosphate for 1 h ( p < 0.05). Furthermore, the degradation of LPS by wheat phytase was nearly unaffected by the addition of L-phenylalanine, the inhibitor of tissue-specific alkaline phosphatase or L-homoarginine, the inhibitor of tissue-non-specific alkaline phosphatase. Wheat phytase effectively reduced the in vitro toxicity of LPS, resulting in a retention of 63% and 54% of its initial toxicity after 1-3 h of the enzyme reaction, respectively ( p < 0.05). Intact LPS decreased the cell viability of HAE cells. However, LPS dephosphorylated by wheat phytase counteracted the inhibitory effect on cell viability. LPS treated with wheat phytase decreased IL-8 secretion from intestinal epithelial cell line, HT-29 cell to 14% ( p < 0.05) when compared with intact LPS. In conclusion, wheat phytase is a potential therapeutic candidate and prophylactic agent for control of infections induced by pathogenic Gram-negative bacteria and associated LPS-mediated inflammatory diseases in animal husbandry., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2021 Korean Society of Animal Science and Technology.)

Coronavirus disease 2019 (COVID-19) and diabetes outcomes (CORONADO) trial revealed that 10.6% of patients with diabetes mellitus hospitalized for COVID-19 (COVID-19) die within 7 days. Several studies from New York, Italy, and China confirm that patients with diabetes are at a much higher risk for mortality due to COVID-19. Besides respiratory illness, COVID-19 increases cardiac injury and diabetic ketoacidosis. In the absence of specific guidelines for the prevention and treatment of COVID-19 for patients with diabetes, they remain at higher risk and are more susceptible to COVID-19. Furthermore, there is a scarcity of basic knowledge on how diabetes affects pathogenesis of severe acute respiratory coronavirus (SARS-CoV-2) infection. In patients with diabetes, impaired glucose use alters metabolic and consequently biological processes instigating pathological remodeling, which has detrimental effects on cardiovascular systems. A majority of biological processes are regulated by noncoding microRNAs (miRNAs), which have emerged as a promising therapeutic candidate for several diseases. In consideration of the higher risk of mortality in patients with diabetes and COVID-19, novel diagnostic test and treatment strategy are urgently warranted in post-COVID-19 era. Here, we describe potential roles of miRNA as a biomarker and therapeutic candidate, especially for heart failure, in patients with diabetes and COVID-19.

Optimum levels of selenoproteins are essential for starting and managing the host immune responses against pathogens. According to the expression of selenoproteins in Leishmania parasites, and since high levels of selenoproteins lead to adverse effects on immune cells and their functions, Leishmania parasites might then express selenoproteins such as selenomethionine in their structure and/or secretions able to challenge the host immune system. Finally, this adaptation may lead to evasion of the parasite from the host immune system. The expression of selenoproteins in Leishmania parasites might then induce the development of infection. We therefore suggest these molecules as new therapeutic candidates for the treatment of leishmaniasis., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.