Targeting microRNAs as a promising anti-cancer therapeutic strategy against traffic-related air pollution-mediated lung cancer.

Air pollutants are increasingly emitted into the atmosphere because of the high dependency of humans on fossil-derived fuels. Wind speed and direction assisted high dispersibility and uncontrolled nature of air pollution across geo-/demographical borders, making it one of the major global concerns. Besides climate change, air pollution has been found to be associated with various diseases, such as cancer. Lung cancer, which is the world's most common type of cancer, has been found to be associated with traffic-related air pollution. Research and political efforts have been taken to explore green/renewable energy sources. However, these efforts at the current intensity cannot cope with the increasing need for fossil fuels. More specifically, political tensions such as the Russian-Ukraine war, economic tension (e.g., China-USA economic tensions), and other issues (e.g., pandemic, higher inflation rate, and poverty) significantly hindered phasing out fossil fuels. In this context, an increasing global population will be exposed to traffic-related air pollution, which justifies the current uptrend in the number of lung cancer patients. To combat this health burden, novel treatments with higher efficiency and specificity must be designed. One of the potential "life changer" options is microRNA (miRNA)-based therapy to target the expression of oncogenic genes. That said, this review discusses the association of traffic-related air pollution with lung cancer, the changes in indigenous miRNAs in the body during lung cancer, and the current status of miRNA therapeutics for lung cancer treatment. We believe that the article will significantly appeal to a broad readership of oncologists, environmentalists, and those who work in the field of (bio)energy. It may also gain the policymakers' attention to establish better health policies and regulations about air pollution, for example, by promoting (bio)fuel exploration, production, and consumption.

The roles of the kynurenine pathway in COVID-19 neuropathogenesis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-ß (IFN-ß), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.

Oncolytic viruses as a promising therapeutic strategy against the detrimental health impacts of air pollution: The case of glioblastoma multiforme.

Human livelihood highly depends on applying different sources of energy whose utilization is associated with air pollution. On the other hand, air pollution may be associated with glioblastoma multiforme (GBM) development. Unlike other environmental causes of cancer (e.g., irradiation), air pollution cannot efficiently be controlled by geographical borders, regulations, and policies. The unavoidable exposure to air pollution can modify cancer incidence and mortality. GBM treatment with chemotherapy or even its surgical removal has proven insufficient (100% recurrence rate; patient's survival mean of 15 months; 90% fatality within five years) due to glioma infiltrative and migratory capacities. Given the barrage of attention and research investments currently plowed into next-generation cancer therapy, oncolytic viruses are perhaps the most vigorously pursued. Provision of an insight into the current state of the research and future direction is essential for stimulating new ideas with the potentials of filling research gaps. This review manuscript aims to overview types of brain cancer, their burden, and different causative agents. It also describes why air pollution is becoming a concerning factor. The different opinions on the association of air pollution with brain cancer are reviewed. It tries to address the significant controversy in this field by hypothesizing the air-pollution-brain-cancer association via inflammation and atopic conditions. The last section of this review deals with the oncolytic viruses, which have been used in, or are still under clinical trials for GBM treatment. Engineered adenoviruses (i.e., DNX-2401, DNX-2440, CRAd8-S-pk7 loaded Neural stem cells), herpes simplex virus type 1 (i.e., HSV-1 C134, HSV-1 rQNestin34.5v.2, HSV-1 G207, HSV-1 M032), measles virus (i.e., MV-CEA), parvovirus (i.e., ParvOryx), poliovirus (i.e., Poliovirus PVSRIPO), reovirus (i.e., pelareorep), moloney murine leukemia virus (i.e., Toca 511 vector), and vaccinia virus (i.e., vaccinia virus TG6002) as possible life-changing alleviations for GBM have been discussed. To the best of our knowledge, this review is the first review that comprehensively discusses both (i) the negative/positive association of air pollution with GBM; and (ii) the application of oncolytic viruses for GBM, including the most recent advances and clinical trials. It is also the first review that addresses the controversies over air pollution and brain cancer association. We believe that the article will significantly appeal to a broad readership of virologists, oncologists, neurologists, environmentalists, and those who work in the field of (bio)energy. Policymakers may also use it to establish better health policies and regulations about air pollution and (bio)fuels exploration, production, and consumption.

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease with a substantial social and economic impact on individuals and their community. Despite its importance and deteriorating impact, progresses in diagnosis and treatment of ME/CFS is limited. This is due to the unclear pathophysiology of the disease and consequently lack of prognostic biomarkers. To investigate pathophysiology of ME/CFS, several potential pathologic hallmarks have been investigated; however, these studies have failed to report a consistent result. These failures in introducing the underlying reason for ME/CFS have stimulated considering other possible contributing mechanisms such as tryptophan (TRP) metabolism and in particular kynurenine pathway (KP). KP plays a central role in cellular energy production through the production of nicotinamide adenine dinucleotide (NADH). In addition, this pathway has been shown to mediate immune response and neuroinflammation through its metabolites. This review, we will discuss the pathology and management of ME/CFS and provide evidence pertaining KP abnormalities and symptoms that are classic characteristics of ME/CFS. Targeting the KP regulation may provide innovative approaches to the management of ME/CFS.

A state-of-the-art review on the application of nanomaterials for enhancing biogas production.

Anaerobic digestion (AD) of organic wastes is among the most promising approaches used for the simultaneous treatment of various waste streams, environment conservation, and renewable bioenergy generation (biomethane). Among the latest innovations investigated to enhance the overall performance of this process both qualitatively and quantitatively, the application of some nanoparticles (NPs) has attracted a great deal of attention. Typically, the NPs of potential benefit to the AD process could be divided into three groups: (i) zero-valent iron (ZVI) NPs, (ii) metallic and metal oxides NPs, and (iii) carbon-based NPs. The present review focuses on the latest findings reported on the application of these NPs in AD process and presents their various mechanisms of action leading to higher or lower biogas production rates. Among the NPs studies, ZVI NPs could be regarded as the most promising nanomaterials for enhancing biogas production through stabilizing the AD process as well as by stimulating the growth of beneficial microorganisms to the AD process and the enzymes involved. Future research should focus on various attributes of NPs when used as additives in biogas production, including facilitating mixing and pumping operations, enriching the population and diversity of beneficial microorganisms for AD, improving biogas release, and inducing the production and activity of AD-related enzymes. The higher volume of methane-enriched biogas would be translated into higher returns on investment and could therefore, result in further growth of the biogas production industry. Nevertheless, efforts should be devoted to decreasing the price of NPs so that the enhanced biogas and methane production (by over 90%, compared to control) would be more economically justified, facilitating the large-scale application of these compounds. In addition to economic considerations, environmental issues are also regarded as major constraints which should be addressed prior to widespread implementation of NP-augmented AD processes. More specifically, the fate of NPs augmented in AD process should be scrutinized to ensure maximal beneficial impacts while adverse environmental/health consequences are minimized.

The kynurenine pathway in traumatic brain injuries and concussion.

Up to 10 million people per annum experience traumatic brain injury (TBI), 80-90% of which are categorized as mild. A hit to the brain can cause TBI, which can lead to secondary brain injuries within minutes to weeks after the initial injury through unknown mechanisms. However, it is assumed that neurochemical changes due to inflammation, excitotoxicity, reactive oxygen species, etc., that are triggered by TBI are associated with the emergence of secondary brain injuries. The kynurenine pathway (KP) is an important pathway that gets significantly overactivated during inflammation. Some KP metabolites such as QUIN have neurotoxic effects suggesting a possible mechanism through which TBI can cause secondary brain injury. That said, this review scrutinizes the potential association between KP and TBI. A more detailed understanding of the changes in KP metabolites during TBI is essential to prevent the onset or at least attenuate the severity of secondary brain injuries. Moreover, this information is crucial for the development of biomarker/s to probe the severity of TBI and predict the risk of secondary brain injuries. Overall, this review tries to fill the knowledge gap about the role of the KP in TBI and highlights the areas that need to be studied.

Current and emerging applications of saccharide-modified chitosan: a critical review.

Chitin, as the main component of the exoskeleton of Arthropoda, is a highly available natural polymer that can be processed into various value-added products. Its most important derivative, i.e., chitosan, comprising ß-1,4-linked 2-amino-2-deoxy-ß-d-glucose (deacetylated d-glucosamine) and N-acetyl-d-glucosamine units, can be prepared via alkaline deacetylation process. Chitosan has been used as a biodegradable, biocompatible, non-antigenic, and nontoxic polymer in some in-vitro applications, but the recently found potentials of chitosan for in-vivo applications based on its biological activities, especially antimicrobial, antioxidant, and anticancer activities, have upgraded the chitosan roles in biomaterials. Chitosan approval, generally recognized as a safe compound by the United States Food and Drug Administration, has attracted much attention toward its possible applications in diverse fields, especially biomedicine and agriculture. Despite some favorable characteristics, the chitosan's structure should be customized for advanced applications, especially due to its drawbacks, such as low drug-load capacity, low solubility, high viscosity, lack of elastic properties, and pH sensitivity. In this context, derivatization with relatively inexpensive and highly available mono- and di-saccharides to soluble branched chitosan has been considered a "game changer". This review critically scrutinizes the emerging technologies based on the synthesis and application of lactose- and galactose-modified chitosan as two important chitosan derivatives. Some characteristics of chitosan derivatives and biological activities have been detailed first to understand the value of these natural polymers. Second, the saccharide modification of chitosan has been discussed briefly. Finally, the applications of lactose- and galactose-modified chitosan have been scrutinized and compared to native chitosan to provide an insight into the current state-of-the research for stimulating new ideas with the potential of filling research gaps.

The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC.

OBJECTIVE: To determine the prevalence and natural history of post-acute COVID-19 objective cognitive impairment and function, and their relationship to demographic, clinical factors, post-acute sequelae of COVID-19 (PASC), and biomarkers. METHODS: A total of 128 post-acute COVID-19 patients (age = 46 ± 15; 42% women, acute disease severity: not hospitalized: 38.6% mild: 0-1 symptoms, 52% 2+ symptoms; 9.4% hospitalized) completed standard cognition, olfaction, and mental health examinations 2-, 4-, and 12-month post diagnosis. Over the same time frame, WHO-defined PASC was determined. Blood cytokines, peripheral neurobiomarkers, and kynurenine pathway (KP) metabolites were measured. Objective cognitive function was demographically/practice corrected, and impairment prevalence was determined using the evidence-based Global Deficit Score method to detect at least mild cognitive impairment (GDS > 0.5). Linear mixed effect regression models with time effect (month post diagnosis) evaluated the relationships to cognition. RESULTS: Across the 12-month study period, mild to moderate cognitive impairment ranged from 16% to 26%, and 46.5% were impaired at least once. Impairment associated with poorer work capacity (p < 0.05), and 2-month objectively tested anosmia (p < 0.05). PASC with (p = 0.01) and without disability (p < 0.03) associated with acute COVID-19 severity. KP measures showed prolonged activation (2 to 8 months) (p < 0.0001) linked to IFN-beta in those with PASC. Of the blood analytes, only the KP metabolites (elevated quinolinic acid, 3-hydroxyanthranilic acid, kynurenine, the kynurenine/tryptophan ratio) associated (p < 0.001) with poorer cognitive performance and greater likelihood of impairment. PASC, independent of disability associated with abnormal kynurenine/tryptophan (p < 0.03). INTERPRETATION: The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC, thereby enabling biomarker and therapeutic possibilities.

The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, complex, and highly debilitating long-term illness. People with ME/CFS are typically unable to carry out their routine activities. Key hallmarks of the disease are neurological and gastrointestinal impairments accompanied by pervasive malaise that is exacerbated after physical and/or mental activity. Currently, there is no validated cure of biomarker signature for this illness. Impaired tryptophan (TRYP) metabolism is thought to play significant role in the pathobiology of ME/CFS. TRYP is an important precursor for serotonin and the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). TRYP has been associated with the development of some parts of the brain responsible for behavioural functions. The main catabolic route for TRYP is the kynurenine pathway (KP). The KP produces NAD+ and several neuroactive metabolites with neuroprotective (i.e., kynurenic acid (KYNA)) and neurotoxic (i.e., quinolinic acid (QUIN)) activities. Hyperactivation of the KP, whether compensatory or a driving mechanism of degeneration can limit the availability of NAD+ and exacerbate the symptoms of ME/CFS. This review discusses the potential association of altered KP metabolism in ME/CFS. The review also evaluates the role of the patient's gut microbiota on TRYP availability and KP activation. We propose that strategies aimed at raising the levels of NAD+ (e.g., using nicotinamide mononucleotide and nicotinamide riboside) may be a promising intervention to overcome symptoms of fatigue and to improve the quality of life in patients with ME/CFS. Future clinical trials should further assess the potential benefits of NAD+ supplements for reducing some of the clinical features of ME/CFS.

Neuropathological Mechanisms of ß-N-Methylamino-L-Alanine (BMAA) with a Focus on Iron Overload and Ferroptosis.

The incidence of neurodegenerative diseases and cyanobacterial blooms is concomitantly increasing worldwide. The cyanotoxin ß-N-methylamino-L-alanine (BMAA) is produced by most of the Cyanobacteria spp. This cyanotoxin is described as a potential environmental etiology factor for some sporadic neurodegenerative diseases. Climate change and eutrophication significantly increase the frequency and intensity of cyanobacterial bloom in water bodies. This review evaluates different neuropathological mechanisms of BMAA at molecular and cellular levels and compares the related studies to provide some useful recommendations. Additionally, the structure and properties of BMAA as well as its microbial origin, especially by gut bacteria, are also briefly covered. Unlike previous reviews, we hypothesize the possible neurotoxic mechanism of BMAA through iron overload. We also discuss the involvement of BMAA in excitotoxicity, TAR DNA-binding protein 43 (TDP-43) translocation and accumulation, tauopathy, and other protein misincorporation and misfolding.

A comprehensive review on anaerobic fungi applications in biofuels production.

Anaerobic fungi (Neocallimastigomycota) are promising lignocellulose-degrading microorganisms that can be exploited by the biofuel industry. While natural production of ethanol by these microorganisms is very low, there is a greater potential for their use in the biogas industry. More specifically, anaerobic fungi can contribute to biogas production by either releasing holocellulose or reducing sugars from lignocelluloses that can be used as a substrate by bacteria and methanogens involved in the anaerobic digestion (AD) process or by metabolizing acetate and formate that can be directly consumed by methanogens. Despite their great potential, the appropriate tools for engineering anaerobic fungi have not been established yet. The first section of this review justifies how the biofuel industry can benefit from using anaerobic fungi and is followed by their taxonomy. In the third section, the possibility of using anaerobic fungi for the consolidated production of bioethanol is briefly discussed. Nevertheless, the main focus of this review is on the upstream and mainstream effects of bioaugmentation with anaerobic fungi on the AD process. The present review also scrutinizes the constraints on the way of efficient engineering of anaerobic rumen fungi. By providing this knowledge, this review aims to help research in this field with identifying the challenges that must be addressed by future experiments to achieve the full potentials of these promising microorganisms. To sum up, the pretreatment of lignocelluloses by anaerobic fungi can prevent carbohydrate loss due to respiration (compared to white-rot fungi). Following fungal mixed acid fermentation, the obtained slurry containing sugars and more susceptible holocellulose can be directly consumed by AD microorganisms (bacteria, methanogens). The bioaugmentation of anaerobic fungi into the AD process can increase methane biosynthesis by >3.3 times. Despite this, for the commercial AD process, novel genetic engineering techniques and kits must be developed to efficiently improve anaerobic fungi viability throughout the AD process.

Engineered bacteria for valorizing lignocellulosic biomass into bioethanol.

Appropriate bioprocessing of lignocellulosic materials into ethanol could address the world's insatiable appetite for energy while mitigating greenhouse gases. Bioethanol is an ideal gasoline extender and is widely used in many countries in blended form with gasoline at specific ratios to improve fuel characteristics and engine performance. Although the bioethanol production industry has long been operational, finding a suitable microbial agent for the efficient conversion of lignocelluloses is still an active field of study. Among available microbial candidates, engineered bacteria may be promising ethanol producers while may show other desired traits such as thermophilic nature and high ethanol tolerance. This review provides the current knowledge on the introduction, overexpression, and deletion of the genes that have been performed in bacterial hosts to achieve higher ethanol yield, production rate and titer, and tolerance. The constraints and possible solutions and economic feasibility of the processes utilizing such engineered strains are also discussed.

Herpetosiphon Secondary Metabolites Inhibit Amyloid-ß Toxicity in Human Primary Astrocytes.

BACKGROUND: The accumulation of extracellular plaques containing amyloid-ß protein (Aß) in the brain is one of the main pathological hallmarks of Alzheimer's disease (AD). Aß peptide can promote the production of highly volatile free radicals and reactive oxygen species (ROS) that can induce oxidative damage to neurons and astrocytes. At present, numerous studies have investigated the neuroprotective and glioprotective effects of natural products derived from plants, animals, and microorganisms. OBJECTIVE: We investigated the glioprotective effect of secondary metabolites obtained from Herpetosiphon sp. HM 1988 against Aß40-induced toxicity in human primary astrocytes. METHODS: The protective effect of bacterial secondary metabolites against Aß40-induced inducible nitric oxide synthase (iNOS) activity was evaluated using the citrulline assay. To confirm the iNOS activity, nitrite production was assessed using the fluorometric Griess diazotization assay. Intracellular NAD+ depletion and lactate dehydrogenase (LDH) release in human primary astrocytes were also examined using well-established spectrophotometric assays. RESULTS: Our results indicate that Aß40 can induce elevation in iNOS and LDH activities, nitrite production, and cellular energy depletion. Importantly, extract of Herpetosiphon sp. HM 1988 decreased iNOS activity, nitrite production, and LDH release. In addition, metabolites of the strain were able to restore cellular energy deficits through inhibition of NAD+ depletion mediated by Aß40. CONCLUSION: These findings suggest that Herpetosiphon metabolites may represent a promising, novel source for the prevention of Aß toxicity in AD.

The Gut Microbiota, Kynurenine Pathway, and Immune System Interaction in the Development of Brain Cancer.

Human gut microbiota contains a large, complex, dynamic microbial community of approximately 1014 microbes from more than 1,000 microbial species, i.e., equivalent to 4 × 106 genes. Numerous evidence links gut microbiota with human health and diseases. Importantly, gut microbiota is involved in the development and function of the brain through a bidirectional pathway termed as the gut-brain axis. Interaction between gut microbiota and immune responses can modulate the development of neuroinflammation and cancer diseases in the brain. With respect of brain cancer, gut microbiota could modify the levels of antioxidants, amyloid protein and lipopolysaccharides, arginase 1, arginine, cytochrome C, granulocyte-macrophage colony-stimulating factor signaling (GM-CSF), IL-4, IL-6, IL-13, IL-17A, interferon gamma (IFN-γ), reactive oxygen species (ROS), reactive nitrogen species (e.g., nitric oxide and peroxynitrite), short-chain fatty acids (SCFAs), tryptophan, and tumor necrosis factor-ß (TGF-ß). Through these modifications, gut microbiota can modulate apoptosis, the aryl hydrocarbon receptor (AhR), autophagy, caspases activation, DNA integrity, microglia dysbiosis, mitochondria permeability, T-cell proliferation and functions, the signal transducer and activator of transcription (STAT) pathways, and tumor cell proliferation and metastasis. The outcome of such interventions could be either oncolytic or oncogenic. This review scrutinizes the oncogenic and oncolytic effects of gut microbiota by classifying the modification mechanisms into (i) amino acid deprivation (arginine and tryptophan); (ii) kynurenine pathway; (iii) microglia dysbiosis; and (iv) myeloid-derived suppressor cells (MDSCs). By delineating the complexity of the gut-microbiota-brain-cancer axis, this review aims to help the research on the development of novel therapeutic strategies that may aid the efficient eradication of brain cancers.

Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status.

The kynurenine pathway is important in cellular energy generation and limiting cellular ageing as it degrades about 90% of dietary tryptophan into the essential co-factor NAD+ (nicotinamide adenine dinucleotide). Prior to the production of NAD+, various intermediate compounds with neuroactivity (kynurenic acid, quinolinic acid) or antioxidant activity (3-hydroxykynurenine, picolinic acid) are synthesized. The kynurenine metabolites can participate in numerous neurodegenerative disorders (Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease) or other diseases such as AIDS, cancer, cardiovascular diseases, inflammation, and irritable bowel syndrome. Recently, the role of gut in affecting the emotional and cognitive centres of the brain has attracted a great deal of attention. In this review, we focus on the bidirectional communication between the gut and the brain, known as the gut-brain axis. The interaction of components of this axis, namely, the gut, its microbiota, and gut pathogens; tryptophan; the kynurenine pathway on tryptophan availability; the regulation of kynurenine metabolite concentration; and diversity and population of gut microbiota, has been considered.

Neuroprotective Effect of Myxobacterial Extracts on Quinolinic Acid-Induced Toxicity in Primary Human Neurons.

Quinolinic acid (QUIN) is a neurotoxin, gliotoxin, and proinflammatory molecule involved in the pathogenesis of several neurological diseases. Myxobacteria have been known as a rich source of secondary metabolites with diverse structures and mode of actions. In this study, we examined the potential neuroprotective effects of myxobacterial extracts on QUIN-induced excitotoxicity in primary human neurons. For this purpose, primary cultures of human neurons were pre-incubated with myxobacterial extracts and subsequently treated with QUIN at a pathophysiological concentration of 550 nM. The results showed that some myxobacterial extracts can significantly attenuate formation of reactive oxygen species (ROS), nitric oxide (NO) production, and extracellular lactate dehydrogenase (LDH) activity of human neurons. Moreover, myxobacterial extracts were also able to reduce neuronal nitric oxide synthase (nNOS) activity. Some extracts prevented cell death by reducing the activation of poly (ADP-ribose) polymerase (PARP1) by QUIN, therefore by maintaining NAD+ levels. In addition, myxobacterial extracts ameliorated oxidative stress by increasing the intracellular levels of glutathione after treatment with QUIN. The results showed that extracts of Stigmatella sp. UTMC 4072 and Archangium sp. UTMC 4070 and were the most effective in reducing QUIN-induced excitotoxicity in primary human neurons. Due to their antioxidative activity, myxobacterial extracts represent an underexplored source of potential new drugs for the treatment of neurodegenerative diseases.

Protective Effects of Myxobacterial Extracts on Hydrogen Peroxide-induced Toxicity on Human Primary Astrocytes.

Astrocytes, the main non-neuronal cells in the brain, have significant roles in the maintenance and survival of neurons. Oxidative stress has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Myxobacteria produce a wide range of bioactive metabolites with notable structures and modes of action, which introduce them as potent natural product producers. In the present study, we evaluated the effects of myxobacterial extracts on hydrogen peroxide (H2O2)-mediated toxicity on primary human astrocytes. We showed that myxobacterial extracts could decrease the formation of reactive oxygen species (ROS), nitric oxide (NO) production, and cell death assessed by the release of lactate dehydrogenase (LDH). Myxobacterial extracts were also able to reduce the nitric oxide synthase (NOS) activity. The extracts reduced the oxidative effect of H2O2 on over-activation of poly (ADP-ribose) polymerase (PARP1), therefore preventing the cell death by restoring the NAD+ levels. In addition, myxobacterial extracts ameliorated the oxidative stress by increasing the glutathione level in cells. The overall results showed myxobacterial extracts, especially from the strains Archangium sp. UTMC 4070 and Cystobacter sp. UTMC 4073, were able to protect human primary astrocytes from oxidative stress.

Human Tick-Borne Diseases in Australia.

There are 17 human-biting ticks known in Australia. The bites of Ixodes holocyclus, Ornithodoros capensis, and Ornithodoros gurneyi can cause paralysis, inflammation, and severe local and systemic reactions in humans, respectively. Six ticks, including Amblyomma triguttatum, Bothriocroton hydrosauri, Haemaphysalis novaeguineae, Ixodes cornuatus, Ixodes holocyclus, and Ixodes tasmani may transmit Coxiella burnetii, Rickettsia australis, Rickettsia honei, or Rickettsia honei subsp. marmionii. These bacterial pathogens cause Q fever, Queensland tick typhus (QTT), Flinders Island spotted fever (FISF), and Australian spotted fever (ASF). It is also believed that babesiosis can be transmitted by ticks to humans in Australia. In addition, Argas robertsi, Haemaphysalis bancrofti, Haemaphysalis longicornis, Ixodes hirsti, Rhipicephalus australis, and Rhipicephalus sanguineus ticks may play active roles in transmission of other pathogens that already exist or could potentially be introduced into Australia. These pathogens include Anaplasma spp., Bartonella spp., Burkholderia spp., Francisella spp., Dera Ghazi Khan virus (DGKV), tick-borne encephalitis virus (TBEV), Lake Clarendon virus (LCV), Saumarez Reef virus (SREV), Upolu virus (UPOV), or Vinegar Hill virus (VINHV). It is important to regularly update clinicians' knowledge about tick-borne infections because these bacteria and arboviruses are pathogens of humans that may cause fatal illness. An increase in the incidence of tick-borne infections of human may be observed in the future due to changes in demography, climate change, and increase in travel and shipments and even migratory patterns of birds or other animals. Moreover, the geographical conditions of Australia are favorable for many exotic ticks, which may become endemic to Australia given an opportunity. There are some human pathogens, such as Rickettsia conorii and Rickettsia rickettsii that are not currently present in Australia, but can be transmitted by some human-biting ticks found in Australia, such as Rhipicephalus sanguineus, if they enter and establish in this country. Despite these threats, our knowledge of Australian ticks and tick-borne diseases is in its infancy.

Myxobacterial natural products: An under-valued source of products for drug discovery for neurological disorders.

Age-related disorders impose noticeable financial and emotional burdens on society. This impact is becoming more prevalent with the increasing incidence of neurodegenerative diseases and is causing critical concerns for treatment of patients worldwide. Parkinson's disease, Alzheimer's disease, multiple sclerosis and motor neuron disease are the most prevalent and the most expensive to treat neurodegenerative diseases globally. Therefore, exploring effective therapies to overcome these disorders is a necessity. Natural products and their derivatives have increasingly attracted attention in drug discovery programs that have identified microorganisms which produce a large range of metabolites with bioactive properties. Myxobacteria, a group of Gram-negative bacteria with large genome size, produce a wide range of secondary metabolites with significant chemical structures and a variety of biological effects. They are potent natural product producers. In this review paper, we attempt to overview some secondary metabolites synthesized by myxobacteria with neuroprotective activity through known mechanisms including production of polyunsaturated fatty acids, reduction of apoptosis, immunomodulation, stress reduction of endoplasmic reticulum, stabilization of microtubules, enzyme inhibition and serotonin receptor modulation.