scholarly journals Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7635
Author(s):  
Nelly Araceli Aburto-Rodríguez ◽  
Naybi Muñoz-Cázares ◽  
Víctor Alberto Castro-Torres ◽  
Bertha González-Pedrajo ◽  
Miguel Díaz-Guerrero ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Significant Inhibition ◽  
Effector Proteins ◽  
World Health ◽  
Swarming Motility ◽  
Chemical Structures ◽  
Public Health Challenges ◽  
C 30 ◽  
Health Organization ◽  
Pathogenic Property

Antimicrobial resistance is one of the current public health challenges to be solved. The World Health Organization (WHO) has urgently called for the development of strategies to expand the increasingly limited antimicrobial arsenal. The development of anti-virulence therapies is a viable option to counteract bacterial infections with the possibility of reducing the generation of resistance. Here we report on the chemical structures of pyrrolidones DEXT 1–4 (previously identified as furan derivatives) and their anti-virulence activity on Pseudomonas aeruginosa strains. DEXT 1–4 were shown to inhibit biofilm formation, swarming motility, and secretion of ExoU and ExoT effector proteins. Also, the anti-pathogenic property of DEXT-3 alone or in combination with furanone C-30 (quorum sensing inhibitor) or MBX-1641 (type III secretion system inhibitor) was analyzed in a model of necrosis induced by P. aeruginosa PA14. All treatments reduced necrosis; however, only the combination of C-30 50 µM with DEXT-3 100 µM showed significant inhibition of bacterial growth in the inoculation area and systemic dispersion. In conclusion, pyrrolidones DEXT 1–4 are chemical structures capable of reducing the pathogenicity of P. aeruginosa and with the potential for the development of anti-virulence combination therapies.

scholarly journals Actinomycetes: A Never-Ending Source of Bioactive Compounds—An Overview on Antibiotics Production

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 483
Author(s):  
Davide De Simeis ◽  
Stefano Serra
Keyword(s):  
Bioactive Compounds ◽  
Bacterial Infections ◽  
New Drugs ◽  
World Health ◽  
Primary Role ◽  
Health Food ◽  
Chemical Structures ◽  
The World ◽  
New Antibiotics ◽  
Health Organization

The discovery of penicillin by Sir Alexander Fleming in 1928 provided us with access to a new class of compounds useful at fighting bacterial infections: antibiotics. Ever since, a number of studies were carried out to find new molecules with the same activity. Microorganisms belonging to Actinobacteria phylum, the Actinomycetes, were the most important sources of antibiotics. Bioactive compounds isolated from this order were also an important inspiration reservoir for pharmaceutical chemists who realized the synthesis of new molecules with antibiotic activity. According to the World Health Organization (WHO), antibiotic resistance is currently one of the biggest threats to global health, food security, and development. The world urgently needs to adopt measures to reduce this risk by finding new antibiotics and changing the way they are used. In this review, we describe the primary role of Actinomycetes in the history of antibiotics. Antibiotics produced by these microorganisms, their bioactivities, and how their chemical structures have inspired generations of scientists working in the synthesis of new drugs are described thoroughly.

scholarly journals World Health Report on Vision: Aging Implications for Global Vision and Eye Health

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 807-808
Author(s):  
Bonnielin Swenor ◽  
Varshini Varadaraj ◽  
Moon Jeong Lee ◽  
Heather Whitson ◽  
Pradeep Ramulu
Keyword(s):  
Older Adults ◽  
Visual Impairment ◽  
Vision Loss ◽  
World Health ◽  
World Health Report ◽  
Global Public Health ◽  
Eye Care ◽  
Health Report ◽  
Public Health Challenges ◽  
Health Organization

Abstract In 2019, the World Health Organization World Report on Vision estimated that that 2.2 billion people have a vision impairment, of which almost half could have been prevented or is yet to be addressed. As the global population ages and the prevalence of visual impairment increases, inequities in eye care and the downstream health and aging consequences of vision loss will become magnified. This session will: (1) provide key information regarding the burden of eye disease and visual impairment among older adults worldwide; (2) outline a framework created to conceptualize the aging and long-term health implications of vision loss, and (3) discuss the global public health challenges to eye care and to maximizing health for older adults with visual impairments.

scholarly journals The Wnt Signalling Pathway: A Tailored Target in Cancer

2020 ◽  
Vol 21 (20) ◽  
pp. 7697 ◽  
Author(s):  
Malvina Koni ◽  
Veronica Pinnarò ◽  
Maria Felice Brizzi
Keyword(s):  
Animal Species ◽  
Current Knowledge ◽  
Integration Site ◽  
World Health ◽  
Cancer Driver ◽  
Common Cancer ◽  
Public Health Challenges ◽  
Health Organization ◽  
Canonical Wnt ◽  
The Impact

Cancer is one of the greatest public health challenges. According to the World Health Organization (WHO), 9.6 million cancer deaths have been reported in 2018. The most common cancers include lung, breast, colorectal, prostate, skin (non-melanoma) and stomach cancer. The unbalance of physiological signalling pathways due to the acquisition of mutations in tumour cells is considered the most common cancer driver. The Wingless-related integration site (Wnt)/β-catenin pathway is crucial for tissue development and homeostasis in all animal species and its dysregulation is one of the most relevant events linked to cancer development and dissemination. The canonical and the non-canonical Wnt/β-catenin pathways are known to control both physiological and pathological processes, including cancer. Herein, the impact of the Wnt/β-catenin cascade in driving cancers from different origin has been examined. Finally, based on the impact of Extracellular Vesicles (EVs) on tumour growth, invasion and chemoresistance, and their role as tumour diagnostic and prognostic tools, an overview of the current knowledge linking EVs to the Wnt/β-catenin pathway is also discussed.

scholarly journals Analysis of the clinical pipeline of treatments for drug resistant bacterial infections: despite progress, more action is needed

2022 ◽  
Author(s):  
Mark S. Butler ◽  
Valeria Gigante ◽  
Hatim Sati ◽  
Sarah Paulin ◽  
Laila Al-Sulaiman ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antibacterial Agents ◽  
Phase 1 ◽  
Clinical Development ◽  
World Health ◽  
Drug Resistant ◽  
Antibacterial Drugs ◽  
Clostridioides Difficile ◽  
Differentiated Candidates ◽  
Health Organization

There is an urgent global need for new strategies and drugs to control and treat multi-drug resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes ‘traditional’ and ‘non-traditional’ antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens, mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3 and four under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile and 4 (5%) are non-traditional agents with broad spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens. We believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.

scholarly journals Use of Natural Products in Leishmaniasis Chemotherapy: An Overview

2020 ◽  
Vol 8 ◽  
Author(s):  
Luiza F. O. Gervazoni ◽  
Gabrielle B. Barcellos ◽  
Taiana Ferreira-Paes ◽  
Elmo E. Almeida-Amaral
Keyword(s):  
Natural Products ◽  
New Drugs ◽  
World Health ◽  
Parasitic Disease ◽  
Research Groups ◽  
Chemical Structures ◽  
Development Of Resistance ◽  
The World ◽  
Health Organization ◽  
Therapeutic Compounds

Leishmaniasis is an infectious parasitic disease that is caused by protozoa of the genus Leishmania, a member of the Trypanosomatidae family. Leishmaniasis is classified by the World Health Organization as a neglected tropical disease that is responsible for millions of deaths worldwide. Although there are many possible treatments for leishmaniasis, these treatments remain mostly ineffective, expensive, and long treatment, as well as causing side effects and leading to the development of resistance. For novel and effective treatments to combat leishmaniasis, many research groups have sought to utilize natural products. In addition to exhibiting potential as therapeutic compounds, natural products may also contribute to the development of new drugs based on their chemical structures. This review presents the most promising natural products, including crude extracts and isolated compounds, employed against Leishmania spp.

Obesity as an infectious disease– review of the literature

2015 ◽  
Vol 51 (1) ◽  
pp. 53-58
Author(s):  
Iwona Bil-Lula ◽  
Anna Krzywonos-Zawadzka
Keyword(s):  
Weight Gain ◽  
Environmental Factors ◽  
World Literature ◽  
Bacterial Infections ◽  
Body Weight Gain ◽  
Therapeutic Strategies ◽  
World Health ◽  
The Central Nervous System ◽  
Health Organization ◽  
Intensive Work

Obesity, which is a pathological and excessive accumulation of body fat (WHO; World Health Organization), is the problem undertaken in the world literature for several decades. Significant mortality due to the obesity comorbidities is the basis to undertake an intensive work on the new preventive and therapeutic strategies worldwide. Nevertheless, due to the multifactorial origin of obesity and the growing number of obese subjects, the effectiveness of these strategies appears to be highly limited. Besides to the traditionally recognized etiological factors of obesity, many reports showing an association of infectious agents and uncontrolled weight gain have been published recently. In this paper we present an overview of reports confirming the association between infections and obesity. Data showed that a specific viral and bacterial infections as well as infections with protozoa and prions are associated with the increased intracellular accumulation of lipids, hypertrophy and hyperplasia of adipose tissue, body weight gain, increase of BMI and changes in lipid metabolism. These infections can serve as direct causal agents, but they can also interact with other environmental factors, thus increasing the predisposition to the development of obesity. There are at least a few hypotheses on the pathogenesis of “infectobesity.” There are some reports describing the damage of the central nervous system and hence the endocrine glands dysfunction due to infection, increased insulin susceptibility of infected cells, reduced production and release of leptin, increased glucose and fatty acids transport into adipocytes and inflammatory basis for infectobesity. Undoubtedly, awareness of the relationship between infections and obesity brings us closer to develop the effective preventive and therapeutic strategies, but it also raises the question about other, so far underestimated, environmental factors that increase the predisposition to obesity.

A review of the two major regulatory pathways for non-proprietary low-molecular-weight heparins

2012 ◽  
Vol 107 (02) ◽  
pp. 201-214 ◽  
Author(s):  
Frederick Ofosu
Keyword(s):  
Molecular Weight ◽  
Drug Application ◽  
World Health ◽  
European Medicines Agency ◽  
Low Molecular Weight ◽  
Regulatory Pathways ◽  
Synthetic Drugs ◽  
Chemical Structures ◽  
Asian Society ◽  
Health Organization

SummaryWith the expiry or pending expiry of originator low-molecular-weight heparin (LMWH) patents, pharmaceutical companies have invested in developing non-proprietary versions of LMWHs. LMWHs are manufactured by depolymerising highly purified unfractionated heparin. In contrast to traditional synthetic drugs with well-defined chemical structures, LMWHs contain complex oligosaccharide mixtures and the different manufacturing processes for LMWHs add to the heterogeneity in their physicochemical properties such that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) consider existing originator LMWHs to be distinct medicinal entities that are not clinically interchangeable. The FDA views LMWHs as drugs and has approved two non-proprietary (generic) LMWHs, using the Abbreviated New Drug Application pathway. In contrast, the World Health Organization and the EMA view LMWHs as biological medicines. Therefore, the EMA and also the Scientific and Standardization Subcommittee on Anticoagulation of the International Society on Thrombosis and Haemostasis and the South Asian Society of Atherosclerosis and Thrombosis have all published specific guidelines for assessing non-proprietary (biosimilar) LMWHs. This manuscript reviews why there are two distinct pathways for approving non-proprietary LMWHs. Available literature on non-proprietary LMWHs approved in some jurisdictions is also reviewed in order to assess whether they satisfy the requirements for LMWHs in the three guidance documents. The review also highlights some of the significant difficulties the two pathways pose for manufacturers and an urgent need to develop a consensus governing the manufacture and regulation of non-proprietary LMWHs to make them more widely available.

scholarly journals Infection prevention measures for orthopaedic departments during the COVID-2019 pandemic: a review of current evidence

2020 ◽  
Vol 1 (4) ◽  
pp. 74-79 ◽  
Author(s):  
Thomas E. Baldock ◽  
Scott M. Bolam ◽  
Ryan Gao ◽  
Mark F. Zhu ◽  
Michael P. J. Rosenfeldt ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Close Contact ◽  
World Health ◽  
Current Evidence ◽  
Cochrane Library ◽  
Personal Protection ◽  
Prevention Measures ◽  
Personal Protection Equipment ◽  
Orthopaedic Surgeons ◽  
Health Organization

Aim The coronavirus disease 2019 (COVID-19) pandemic presents significant challenges to healthcare systems globally. Orthopaedic surgeons are at risk of contracting COVID-19 due to their close contact with patients in both outpatient and theatre environments. The aim of this review was to perform a literature review, including articles of other coronaviruses, to formulate guidelines for orthopaedic healthcare staff. Methods A search of Medline, EMBASE, the Cochrane Library, World Health Organization (WHO), and Centers for Disease Control and Prevention (CDC) databases was performed encompassing a variety of terms including ‘coronavirus’, ‘covid-19’, ‘orthopaedic’, ‘personal protective environment’ and ‘PPE’. Online database searches identified 354 articles. Articles were included if they studied any of the other coronaviruses or if the basic science could potentially applied to COVID-19 (i.e. use of an inactivated virus with a similar diameter to COVID-19). Two reviewers independently identified and screened articles based on the titles and abstracts. 274 were subsequently excluded, with 80 full-text articles retrieved and assessed for eligibility. Of these, 66 were excluded as they compared personal protection equipment to no personal protection equipment or referred to prevention measures in the context of bacterial infections. Results There is a paucity of high quality evidence surrounding COVID-19. This review collates evidence from previous coronavirus outbreaks to put forward recommendations for orthopaedic surgeons during the COVID-19 pandemic. The key findings have been summarized and interpreted for application to the orthopaedic operative setting. Conclusion For COVID-19 positive patients, minimum suggested PPE includes N95 respirator, goggles, face shield, gown, double gloves, and surgical balaclava. Space suits not advised. Be trained in the correct technique of donning and doffing PPE. Use negative pressure theatres if available. Minimize aerosolization and its effects (smoke evacuation and no pulse lavage). Minimize further unnecessary patient-staff contact (dissolvable sutures, clear dressings, split casts).

scholarly journals Prophylaxis and Treatment against Klebsiella pneumoniae: Current Insights on This Emerging Anti-Microbial Resistant Global Threat

2021 ◽  
Vol 22 (8) ◽  
pp. 4042
Author(s):  
Vanessa Arato ◽  
Maria Michelina Raso ◽  
Gianmarco Gasperini ◽  
Francesco Berlanda Scorza ◽  
Francesca Micoli
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Outer Membrane Proteins ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
World Health ◽  
Current Status ◽  
Middle Income ◽  
Health Organization ◽  
Global Threat

Klebsiella pneumoniae (Kp) is an opportunistic pathogen and the leading cause of healthcare-associated infections, mostly affecting subjects with compromised immune systems or suffering from concurrent bacterial infections. However, the dramatic increase in hypervirulent strains and the emergence of new multidrug-resistant clones resulted in Kp occurrence among previously healthy people and in increased morbidity and mortality, including neonatal sepsis and death across low- and middle-income countries. As a consequence, carbapenem-resistant and extended spectrum β-lactamase-producing Kp have been prioritized as a critical anti-microbial resistance threat by the World Health Organization and this has renewed the interest of the scientific community in developing a vaccine as well as treatments alternative to the now ineffective antibiotics. Capsule polysaccharide is the most important virulence factor of Kp and plays major roles in the pathogenesis but its high variability (more than 100 different types have been reported) makes the identification of a universal treatment or prevention strategy very challenging. However, less variable virulence factors such as the O-Antigen, outer membrane proteins as fimbriae and siderophores might also be key players in the fight against Kp infections. Here, we review elements of the current status of the epidemiology and the molecular pathogenesis of Kp and explore specific bacterial antigens as potential targets for both prophylactic and therapeutic solutions.

scholarly journals Anti-Inflammatory, Antiallergic, and COVID-19 Main Protease (Mpro) Inhibitory Activities of Butenolides from a Marine-Derived Fungus Aspergillus terreus

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3354
Author(s):  
Ibrahim Seyda Uras ◽  
Sherif S. Ebada ◽  
Michal Korinek ◽  
Amgad Albohy ◽  
Basma S. Abdulrazik ◽  
...  
Keyword(s):  
Aspergillus Terreus ◽  
2D Nmr ◽  
World Health ◽  
Chemical Structures ◽  
Main Protease ◽  
The World ◽  
Inhibitory Activities ◽  
Anti Inflammatory ◽  
Health Organization

In December 2020, the U.K. authorities reported to the World Health Organization (WHO) that a new COVID-19 variant, considered to be a variant under investigation from December 2020 (VUI-202012/01), was identified through viral genomic sequencing. Although several other mutants were previously reported, VUI-202012/01 proved to be about 70% more transmissible. Hence, the usefulness and effectiveness of the newly U.S. Food and Drug Administration (FDA)-approved COVID-19 vaccines against these new variants are doubtfully questioned. As a result of these unexpected mutants from COVID-19 and due to lack of time, much research interest is directed toward assessing secondary metabolites as potential candidates for developing lead pharmaceuticals. In this study, a marine-derived fungus Aspergillus terreus was investigated, affording two butenolide derivatives, butyrolactones I (1) and III (2), a meroterpenoid, terretonin (3), and 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde (4). Chemical structures were unambiguously determined based on mass spectrometry and extensive 1D/2D NMR analyses experiments. Compounds (1–4) were assessed for their in vitro anti-inflammatory, antiallergic, and in silico COVID-19 main protease (Mpro) and elastase inhibitory activities. Among the tested compounds, only 1 revealed significant activities comparable to or even more potent than respective standard drugs, which makes butyrolactone I (1) a potential lead entity for developing a new remedy to treat and/or control the currently devastating and deadly effects of COVID-19 pandemic and elastase-related inflammatory complications.

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