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Developing numerous nanotechnological designed tools to monitor the existence of SARS-CoV-2, and modifying its interactions address the global needs for efficient remedies required for the management of COVID-19. Herein, through a multidisciplinary outlook encompassing different fields such as the pathophysiology of SARS-CoV-2, analysis of symptoms, and statistics of neurological complications caused by SARS-CoV-2 infection in the central and peripheral nervous systems have been testified. The anosmia (51.1%) and ageusia (45.5%) are reported the most frequent neurological manifestation. Cerebrovascular disease and encephalopathy were mainly related to severe clinical cases. In addition, we focus especially on the various concerned physiological routes, including BBB dysfunction, which transpired due to SARS-CoV-2 infection, direct and indirect effects of the virus on the brain, and also, the plausible mechanisms of viral entry to the nerve system. We also outline the characterisation, and the ongoing pharmaceutical applications of quantum dots as smart nanocarriers crossing the blood-brain barrier and their importance in neurological diseases, mainly SARS-CoV-2 related manifestations Moreover, the market status, six clinical trials recruiting quantum dots, and the challenges limiting the clinical application of QDs are highlighted.

Myxobacteria have been mainly mining for their drug-like compounds while their essential and versatile protease enzymes is less explored. In this study, in order to obtain myxobacterial strains wit...

AIMS The persipeptides were recognized as a promising source of multiple pharmaceutical activities which were revealed following structure-activity prediction and examination in experimental analysis. METHODS AND RESULTS The profile of toxicity, antioxidant, anti-inflammatory, anti-diabetic and anti-ageing activity of persipeptides and the crude extract were evaluated experimentally. The pure Persipeptide A and B revealed a moderate xanthine oxidase inhibition activity at the concentration of 10 µg/ml. Persipeptide exhibited α-glucosidase inhibition activity (~10% inhibition) and less than 2% tyrosinase inhibition activity at the concentration of 10 µg/ml. The extract exhibited the inhibition of less than 2% acetylcholine esterase inhibition activity, but the pure persipeptide showed 6%-14% inhibition activity at the concentration of 10 µg/ml. The molecular docking analysis revealed that the activities of Persipeptide A and B are due to interaction with xanthin oxidase, α-amylase, α-glucosidase, tyrosinase and acetylcholine esterase enzymes. CONCLUSIONS The persipeptides showed a similar inhibition rate with positive control that might imply its potential as an anti-diabetic and anti-gout compound among. Only acetylcholine esterase inhibition of persipeptide was higher than the extract. The interacting amino acids of the molecules with different targets show that persipeptides might have antioxidant, anti-inflammatory, anti-diabetic, anti-ageing activity and even other potential pharmaceutical activities that were not investigated in this study. SIGNIFICANCE AND IMPACT OF THE STUDY This report was presented to find some new pharmaceutical activities of Persipeptide A and B including the α-glucosidase inhibition activity as a molecular target of diabetes mellitus. Persipeptides also exhibited an effective inhibition of xanthine oxidase (XO) which can be a drug-like candidate in the treatment of diseases associated with XO like gout. The binding values indicated the interaction of persipeptides with these enzymes.

In addition to the typical respiratory manifestations, various disorders including involvement of the nerve system have been detected in COVID-19 ranging from 22 to 36%. Although growing records are focusing on neurological aspects of COVID-19, the pathophysiological mechanisms and related therapeutic methods remain obscure. Considering the increased concerns of SARS-CoV-2 potential for more serious neuroinvasion conditions, the present review attempts to focus on the neuroprotective effects of natural compounds as the principle source of therapeutics inhibiting multiple steps of the SARS-CoV-2 infection cycle. The great majority of the natural products with anti-SARS-CoV-2 activity mainly inhibit the attachment, entry and gene expression rather than the replication, assembly, or release. Although microbial-derived natural products comprise 38.5% of the known natural products with neuroprotective effects following viral infection, the neuroprotective potential of the majority of microorganisms is still undiscovered. Among natural products, chrysin, huperzine A, ginsenoside Rg1, pterostilbene, and terrein have shown potent in vitro neuroprotective activity and can be promising for new or repurpose drugs for neurological complications of SARS-CoV-2.

Recently, emerged outbreaks of various viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MERS-CoV, and ZIKA infections, are fatal for human life. These life-threatening infections to public health pointed out as a major cause responsible for initiating severe diseases globally. These viral infections heightened the morbidity rates and thus, it is a deadly fear to human life. Researchers left no stone unturned for searching newer therapeutic targets and remedies to treat these viral infections and outbreaks. Simultaneously, some of the researchers have gained success in the discovery of an efficient treatment and development of an effective vaccine [1]. In view of that, numerous developments have been made for innovating nanotherapies, which can treat viral infection and few of them are written off as nanomedicine, have been become reality.

Diabetes is on the rise across the globe affecting more than 463 million people and crucially increasing morbidities of diabetes-associated diseases. Urgent and immense actions are needed to improve diabetes prevention and treatment. Regarding the correlation of diabetes with many associated diseases, inhibition of the disease progression is more crucial than controlling symptoms. Currently, anti-diabetic drugs are accompanied by undesirable side-effects and target confined types of biomolecules. Thus, extensive research is demanding to identify novel disease mechanisms and molecular targets as probable candidates for effective treatment of diabetes. This review discusses the conventional molecule targets that have been applied for their therapeutic rationale in treatment of diabetes. Further, the emerging and prospective molecular targets for the future focus of library screenings are presented.

Natural products (NPs) are a valuable source in the food, pharmaceutical, agricultural, environmental, and many other industrial sectors. Their beneficial properties along with their potential toxicities make the detection, determination or quantification of NPs essential for their application. The advanced instrumental methods require time-consuming sample preparation and analysis. In contrast, biosensors allow rapid detection of NPs, especially in complex media, and are the preferred choice of detection when speed and high throughput are intended. Here, we review diverse biosensors reported for the detection of NPs. The emerging approaches for improving the efficiency of biosensors, such as microfluidics, nanotechnology, and magnetic beads, are also discussed. The simultaneous use of two detection techniques is suggested as a robust strategy for precise detection of a specific NP with structural complexity in complicated matrices. The parallel detection of a variety of NPs structures or biological activities in a mixture of extract in a single detection phase is among the anticipated future advancements in this field which can be achieved using multisystem biosensors applying multiple flow cells, sensing elements, and detection mechanisms on miniaturized folded chips.

The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS‐CoV‐2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS‐CoV‐2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of anti‐viral targets are applicable for SARS‐CoV‐2 drug screenings, the more promising targets can be considered as 3C‐like main protease (3Cl protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS‐CoV‐2. The known molecular targets of the SARS‐CoV‐2 include fourteen targets, while four molecules of angiotensin‐converting enzyme 2 (ACE2), cathepsin L, 3Cl protease and RNA‐dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual‐acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS‐CoV‐2 infection and virus entry‐related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS‐CoV‐2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS‐CoV‐2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti‐SARS‐CoV‐2 drug discovery.

Oral biofilm formation by Streptococcus mutans as a critical and the predominant causative agent of several dental and physiologic disorders needs to be tackled. Investigating anti-biofilm compounds from marine Actinobacteria as a source of natural product for blocking the biofilm formation by Streptococcus mutans was conducted. Anti-adhesion activity of Actinobacterial extracts was investigated through crystal violet assay. Herein, the extract of Glycomyces sediminimaris UTMC 2460 (DSM 103727) prevented the adhesion potency of S. mutans up to 95.1% at 100 𝜇g/mL. The Extracellular Polymeric Substance (EPS) production and cell hydrophobicity index of the strain was restrained up to 66% and 30%, respectively. The extract showed metabolism suppression up to 20% in S. mutans even in the biofilm state at the effective biofilm inhibition concentration (100 𝜇g/mL). Metabolic profiling of Glycomyces sediminimaris revealed the presence of anti-biofilm diketopiperazines compounds as major components of the extract. The current finding postulate that the metabolic profile of marine Glycomyces sediminimaris includes biocompounds that can be evaluated in further studies as an anti-biofilm of S.mutans which has not been previously reported.

The worldwide COVID-19 pandemic has brought significant consideration toward innovative strategies for overcoming the viral spread. Nanotechnology will change our lives in several forms as its uses span from electronics to pharmaceutical procedures. The use of nanoparticles provides a possibility to promote new antiviral treatments with a low possibility of increasing drug resistance compared to typical chemical-based antiviral treatments. Since the long-term usage of disinfectants and antiseptics at high concentrations has deleterious impacts on well-being and the environment, this review was intended to discuss the antiviral activity of disinfectants and antiseptics required for their activity against respiratory viruses especially SARS-CoV-2. It could improve the inhibition of viral penetration into cells, solvation of the lipid bilayer envelope, and ROS production, therefore enhancing the effect of disinfectants. However, significant concerns about nanomaterial's hazardous effects on individuals and the environment are increasing as nanotechnology flourishes. In this review, we first discuss the significant and essential types of nanomaterials, especially silver and copper, that could be used as antiviral agents and their viral entry mechanisms into host cells. Further, we consider the toxicity on health, and environmental concerns of nanoparticles. Eventually, we present our outlook on the fate of nanomaterials toward viral diseases.

Thiopeptides are ribosomally biosynthesized and post-translationally modified peptides (RiPPs) that potently inhibit the growth of Gram-positive bacteria by targeting multiple steps in protein biosynthesis. The poor pharmacological properties of thiopeptides, in particular their low aqueous solubility, has hindered their development into clinically useful antibiotics. Antimicrobial activity screens of a library of Actinobacterial extracts led to discovery of the novel polyglycosylated thiopeptides persiathiacins A and B from Actinokineospora sp. UTMC 2475 and Actinokineospora sp. UTMC 2448. Persiathiacin A is active against methicillin-resistant Staphylococcus aureus (MRSA) and several Mycobacterium tuberculosis strains, including drug-resistant and multidrug-resistant clinical isolates, and does not significantly affect the growth of ovarian cancer cells at concentrations up to 400 μM. In vitro translation assays showed that, like other thiopeptide antibiotics, persiathiacin A targets protein biosynthesis. Polyglycosylated thiopeptides are extremely rare and nothing is known about their biosynthesis. Sequencing and analysis of the Actinokineospora sp. UTMC 2448 genome enabled identification of the putative persiathiacin biosynthetic gene cluster. A cytochrome P450 encoded by this gene cluster catalyses the hydroxylation of nosiheptide in vitro and in vivo, consistent with the proposal that the cluster directs persiathiacin biosynthesis. Several genes in the cluster encode homologues of enzymes known to catalyse the assembly and attachment of deoxysugars during the biosynthesis of other classes of glycosylated natural products. The discovery of the persiathiacins and their biosynthetic gene cluster thus provides the basis for the development of biosynthetic engineering approaches to the creation of novel (poly)glycosylated thiopeptide derivatives with enhanced pharmacological properties.

Drug resistance is a critical issue in future clinical treatment. Methicillin-resistant Staphylococcus aureus (MRSA) is among the pathogens that need indispensable drug-discovery efforts. The myxobacteria are a unique group of bacteria that have recently been regarded for their potency to produce new drugs with high chemical diversity and unusual mode of actions. The present study was conducted to isolate and screen myxobacteria for the first time from Iran habitats and evaluate their antibacterial activity against the multidrug-resistant strain of S. aureus. Out of 62 soil and rotten plant samples, 51 myxobacteria were isolated. The isolates belonged to Myxococcus, Corallococcus, Pyxidicoccus, and Cystobacter genera based on morphology and 16S rRNA gene sequencing. Secondary metabolites of the selected strains were screened for activity on MDR strain with resistance to multiple antibiotic classes. The semi-purified fraction from Cystobacter sp. UTMC 4086 showed potent activity against MDR S. aureus with minimum inhibitory effect at 5 ≥ μg per mL compared with vancomycin (5 μg per mL) as well as no toxicity against Artemia salina. Hence, the strain Cystobacter sp. UTMC 4086 can be a valuable candidate for antibiotic discovery against MRSA and its metabolites can be subjected to further purification and analysis aimed at the identification of the effective chemical entity.

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.

Background The year 2020 has been through the occurrence of a pandemic caused by a virus known as SARS-CoV-2. The uncontrolled worldwide spread of COVID-19 and the rapid transmission of this virus lead to more and more cases, which results in a massive data stream. Each day a new set of data points are being reported regarding the number of positive test results, patients hospitalized, deaths, ventilator shortages, etc. This paper reviews Blockchain technology principles that suit it for data sharing of the pandemic and highlights the potential applications and opportunities in allying this form of data deposition and sharing for combating the COVID-19 pandemic. Results Blockchain has potential application in rapid data sharing of COVID-19 associated data. Data sharing using Blockchain is among the most influencing and practical approaches that healthcare data management can utilize to be more efficacious. Despite Blockchain robustness, it still has limitations that need to be considered in this paper. Conclusions The key concept of Blockchain technology is decentralization, which provides high performance and security for records stored on the net. Moreover, Blockchain is accessible to every participating block in the network. As a result, Blockchain can play an important role in storing and sharing medical records by giving global secure access to trusted data.

Background The long-term use of Chlorhexidine (CHG) at high concentrations has detrimental effects on health and the environment. This research was aimed to evaluate the antibacterial capacity of CHG in the presence of choline as a natural additive to reduce the amount CHG required for the activity. Methods The newly obtained formulation was evaluated for its stability and efficiency under physicochemical stresses. The checkerboard test was also performed to evaluate the type of CHG-additive interaction in a combinational state. Results The MIC of CHG was reduced up to five-fold in combination with choline at the concentration of 50mg/L and five log cfu/mL at 3 minutes of exposure. Chlorhexidine activity in combination with choline was preserved 20% more in the presence of interfering substances. The activity between CHG and choline was demonstrated as synergistic with FICI of 0.375. At sub MIC concentrations of both CHG (≤20 mg/L) and choline (≤6 mg/L) the observed interaction was synergy. While the significant interaction at high concentrations for both compounds was indifferent manner. The lysis effect of the CHG 20 mg/L was diminished in the presence of choline. Conclusions Our suggested CHG formulation demonstrated rapid antimicrobial efficacy which can be a useful adjunct to infection control strategies currently employed in healthcare facilities. In conclusion, CHG can be combined with natural compounds as additives for enhanced synergistic antimicrobial activity.

Age and diabetes related slow-healing or chronic wounds may result in morbidity and mortality through persistent biofilms infections and prolonged inflammatory phase. Nano-materials [metal/metal oxide NPs (39%), lipid vehicles (21%), polymer NPs (19%), ceramic nanoparticles (NPs) (14%), and carbon nanomaterials (NMs) (7%)] can be introduced as a possible next-generation therapy because of either their intrinsic wound healing activity or via carrying bioactive compounds including, antibiotics, antioxidants, growth factor or stem cell. The nanomaterials have been shown to implicate in all four stages of wound healing including hemostasis (polymer NPs, ceramic NPs, nanoceria-6.1%), inflammation (liposome/ vesicles/ solid lipid NPs/ polymer NPs/ ceramic NPs/ silver NPs/ gold NPs/ nanoceria/ fullerenes/ carbon-based NPs-32.7%), proliferation (vesicles/ liposome/ solid lipid NPs/ gold NPs/ silver NPs/ iron oxide NPs/ceramic NPs/ copper NPs / self-assembling elastin-like NPs/ nanoceria/ micelle/ dendrimers/ polymer NPs-57.1%), remodeling (iron oxide NPs/ nanoceria-4.1%). Natural compounds from alkaloids, flavonoids, retinoids, volatile oil, terpenes, carotenoids, or polyphenolic compounds with proven antioxidant, anti-inflammatory, immunomodulatory, or antimicrobial characteristics are also well known for their potential to accelerate the wound healing process. In the current paper, we survey the potential and properties of nanomaterials and microbial compounds in improving the process of wound and scar healing. Finally, we review the potential biocompounds for incorporation to nano-material in perspective to designate more effective or multivalent wound healing natural or nano-based drugs.

Monitoring toxigenic cyanobacteria in freshwaters is of great importance due to the adverse health impacts on humans and aquatic organisms. Here we studied cyanobacterial occurrence and biodiversity in a drinking water reservoir in Tehran province, Iran. In total, nine different species representing three orders of Synechococcales, Oscillatoriales and Nostocales were isolated and classified into six families and seven genera ranging from 92.3% to 99.0% similarities in their partial 16S rDNA with GenBank sequences. The cultures were analyzed for cyanotoxins production by the Artemia salina bioassay, ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and also screened for the presence of marker genes involved in toxins production. Ethyl acetate extracts of three strains showed more than 50% mortality on A. salina larvae after 24 h at a concentration of 500 µg/ml. Production of at least one of the cyanotoxins, microcystin (MC), cylindrospermopsin (CYN) and anatoxin-a (ATX-a), was detected in 6 of the strains. Seven MC variants with a total concentration of 130.6 ng/mg of biomass dry weight were detected for the strain Phormidium sp. UTMC6001 and molecular screening of the mcyE gene also confirmed the presence of this biomarker in its genome. Our study also revealed the production of CYN in a novel picocyanobacterial strain Cyanobium sp. UTMC6007 at 1.0 ng/mg of biomass dry weight. Considering the limited information on freshwater toxic cyanobacteria taxonomy in the Middle East, these findings will expand our knowledge and consequently aid in development of new water management policies in future.

Designing novel isolation methods could enhance the diversification of the available bacterial strains to biotechnology. In this study, the new ex situ and in situ cultivation methods are introduced for the isolation of actinobacteria. In the ex situ experiments, the soil suspension was spread on the isolation media located above some ordinary papers in immediate contact with the slurry of soil substrate and incubated for 16 weeks. The paper was wholly immersed in the cave soil for in situ cultivations, and the containers were buried under layers of soil in Hampoeil cave for 10 weeks. Fruit wrapping kraft coated paper, with 68.8% recovery of isolates, was a better choice in isolation of actinobacteria than other studied filter paper. Based on the molecular identification results, 19% of the isolates obtained from the in situ cultivation method had less than 98.5% similarity to known taxa of actinobacteria and potentially may represent new species. In contrast, in the standard cultivation method, 1.3% of the isolates had less than 98.5% similarity 16Sr RNA gene. This data shows that the introduced cultivation method is a promising technique for isolating less culturable or new actinobacteria.

The transmission control of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the most effective strategy by the absence of its specified vaccine or drug. Although the aerosol mediated transmission of SARS‐CoV‐2 has been confirmed, the physicochemical treatment of the biotic and abiotic objects is still the most promising approach in its infection control. The front line of the most effective disinfecting compounds on SARS‐CoV‐2 implies to be sodium hypochlorite, ethanol, hydrogen peroxide, quaternary ammonium compounds, and phenolic compounds, respectively. However, widely used compounds of alkyldimethylbenzylammonium chloride (benzalkonium chloride) biguanides (chlorhexidine) have not shown the multitude load reduction in less than 10 minutes. The susceptibility of SARS‐CoV‐2 to physical treatment follows the pattern of heat, acidity, and UV radiation. Rather all of the mentioned physical or chemical treatments, target the envelope proteins of the coronavirus mainly by impairing its entry to host cells. The anti‐SARS‐CoV‐2 activity of combinatorial physicochemical treatments or evaluation of new chemical entities or physical treatments such as microwave irradiation still needs to be explored. Therefore, the development of a reliable decontamination protocol for SARS‐CoV‐2 demands revealing its stability pattern study vs a spectrum of single and combinatorial physicochemical parameters.

Inflammation is a complex pathophysiological process associated with atherosclerosis, cancers, diabetes, osteoporosis, rheumatoid arthritis, cardiovascular and autoimmune diseases. In this review, we represent an overview of microbial-derived compounds, and nanomaterial with anti-inflammatory activity and compare their efficiency, mode actions, and limitations. This paper aims to provide an insight on possible approaches to expand the chemical space of anti-inflammatory drugs. The micro-based approach through the discovery of new anti-inflammatory compounds from microorganisms and nano-based approach through the augmentation by nanomaterials are among the main suggested natural and chemical resources to provide new anti-inflammation drugs in the future. Furthermore, some nanomaterials by improving the anti-inflammatory properties of commercial drugs or microbial compounds through enhancing their solubility, decreasing unfavorable effects, donating excellent targeting, allowing a lower dosage, and providing substitute less-invasive delivery routes, have shown their indirect anti-inflammatory activity. Additionally, the efficiency of existing drugs can also be modulated by using new synergistic anti-inflammatory compounds from microorganisms or modification/augmentation by nanomaterials. This will aid in designing new nano and bio-based medications for the prevention and treatment of numerous inflammation related-debilitating diseases.

The drug discovery rate is dramatically decreasing due to the rediscovery of known compounds. Genome mining approaches have revealed that a large portion of the actinobacterial genome that encodes bioactive metabolites is cryptic and not expressed under standard lab conditions. In the present study, we aimed to induce antibiotic encoding biosynthetic genes in a member of Micrococcales as a new species of Promicromonospora, Promicromonospora kermanensis, by chemical and biological elicitors as it was considered to produce numerous valuable bioactive metabolites based on the whole genome results. Induction has been done via chemical (antibiotics, histone deacetylase inhibitors (HDAIs), rare earth elements (REEs), fatty acid synthesis inhibitors, and extreme pH changes) and biological elicitors (live and dead Gram-positive and negative bacteria). The results showed that valproic acid (as HDAIs), DMSO, lanthanum chloride (as REE), triclosan (as fatty acid synthesis inhibitors), alkaline pH, and supernatant of Pseudomonas aeruginosa UTMC 1404 culture could act as stimuli to provoke antibacterial synthetic pathways in Promicromonospora kermanensis DSM 45485. Moreover, it was revealed that eliciting agents in cell filtrated of P. aeruginosa culture is resistant to detergent, acidic, and basic condition and have amphipathic nature. The inducing effect of alkaline pH on metabolite induction of Actinobacteria was first reported in this study. In the follow-up studies, the induced antibacterial producing clusters can be subjected to the characterization, and the implemented approach in this study can be used for metabolites induction in other selected species.

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.

Aim Alzheimer's disease (AD) is the most common cause of dementia. The acetylcholinesterase (AChE) inhibitors are the most viable therapeutic target for its symptomatic treatment. The present study was aimed at exploring anti-AChE metabolite producing marine Actinobacteria. Methods and results Of 220 isolates, 34 Actinobacteria extracts were tested for the presence of AChE inhibitors. The obtained results showed that bacterial strain UTMC 1334, inhibited AChE activity in a dose-dependent manner (IC50 = 0·36 ± 0·019 mg ml-1 ). Based on anti-oxidant and cytotoxicity studies, the most potent extract was able to scavenge DPPH radicals with an IC50 value of 45·67 μg ml-1 with the least cytotoxicity. The GC-MS analysis demonstrated that the mentioned activities could be related to pyrrole-derived compounds as were found the predominant constituents in the extract. The most active extract belonged to the strain that shows 99·41% similarity with Streptomyces lateritius based on 16S rRNA gene sequencing. Conclusions Our results show anti-AChE activity is prevalent in marine Actinobacteria, and even in rather comparable prevalence with the antibiotics. Significance and impact of the study This study highlights that exploring new lead anti-AChE compounds may result in discovering novel adjuvant candidates with potency in the treatment of cognitive diseases such as AD.

A novel Glycomyces strain, designated as MH2460T, was isolated from marine sediment collected from 12 m depth in Rostami seaport, Bushehr Province in Iran. On International Streptomyces Project 2 medium it produced branching substrate hyphae that developed into a large number of irregularly shaped spores in 8 days. It showed optimal growth at 25–35 °C, pH 6.0–8.0 and in salinity between 2.5–5 % (w/v) NaCl. Chemotaxonomic and molecular characteristics of the isolate matched descriptions for members of the genus Glycomyces . Whole-cell hydrolysates of strain MH2460T contained meso-diaminopimelic acids along with glucose, ribose and small traces of xylose and galactose. The phospholipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides as well as two unidentified phosphoglycolipids, one unidentified phospholipid and an unidentified aminolipid. The predominant menaquinones were MK-11(H4) and MK-10(H4). The fatty-acid pattern was mainly composed of anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C16 : 0. The strain belongs to the genus Glycomyces based on 16S rRNA gene sequence with the highest pairwise sequence identity (98.3 %) with Glycomyces phytohabitans KLBMP 1483T. The DNA–DNA hybridization value showed 53.9±2.7 % identity when MH2460T was compared to this reference strain. The G+C content of the DNA was 70.2 mol%. Based on phenotypic, biochemical, chemotaxonomic and genotypic features, strain MH2460T (DSM 103727T=UTMC 2460T=NCCB 100631T) is considered to represent a novel species of the genus Glycomyces , for which the name Glycomyces sediminimaris is proposed.

Aim: To simplify the recognition of Actinobacteria, at different stages of the growth phase, from a mixed culture to facilitate the isolation of novel strains of these bacteria for drug discovery purposes. Materials & methods: A method was developed based on Gabor transform, and machine learning using k-Nearest Neighbors and Naive Bayes classifier, Logitboost, Bagging and Random Forest to automatically categorize the colonies. Results: A signature pattern was inferred by the model, making the differentiation of identical strains possible. Additionally, higher performance, compared with other classification methods was achieved. Conclusion: This automated approach can contribute to the acceleration of the drug discovery process while it simultaneously can diminish the loss of budget due to the redundancy occurred by the inexperienced researchers.

Aging is an inevitable process caused by the accumulation of degenerative destructions, which ultimately leads to organism death. As the aging process occurs at the molecular, cellular, and tissue levels, understanding the whole details of age-related disorders is the prerequisite for the development of anti-aging therapy. More than 300 compounds of different sources have been reported with an anti-aging activity that controls age-related diseases through regulating single or multiple signalling pathways. Recent innovations in nanotechniques could lead to the development of nanomaterials having effects on age-associated malfunctions or acting as nanocarrier systems and distributers of anti-aging drugs. In this review, we summarised the molecular mechanisms of longevity and the prospect of developing anti-aging nanomaterials targeting aging pathways.

Context: Actinobacteria are a precious source of novel bioactive metabolites with potential pharmaceutical applications. Objectives: Representatives of 11 genera of rare Actinobacteria were selected for the evaluation of antioxidant activity. Material and methods: Fermentation broths of the Actinobacteria were extracted and dosage of 10 to 2000 µg/mL were applied for in vitro antioxidant-related bioassays. Cytotoxicity was assessed at the concentration of 2.5–20 µg/mL. Results: In the DPPH scavenging activity, 15 out of 52 extracts showed 17.0–26.8% activity in quantitative evaluation. Metabolites of five prominent antioxidant producing strains protected the DNA (pUC19) against UV-induced photolyzed H2O2-oxidative degradation. The potent antioxidant extracts inhibited two oxidative enzymes of xanthine oxidase in the range of 17.5–45.2% (three extracts had IC50 less than allopurinol) and lipoxygenase in the range of 36–55% (all five extracts had IC50 values less than daidzein). All these extracts could also protect eythrocytes from iron-induced hemolysis with ED50 values in a range of 0.014–1.25 mg/mL. Growth restoration of the yeast cells lacking the sod1 gene was observed by the antioxidant metabolite of Saccharothrix ecbatanensis UTMC 537 at the concentration of 1 mg/mL. Conclusions: The presence of nonidentical metabolites might be responsible for antioxidant and enzyme inhibitory activities of S. ecbatanensis, newly described actinobacterium in family Pseudonocardiaceae. The scavenging of the free electrons, protection of DNA and model yeast cells against oxidative stress, in addition to the inhibition of the oxidating enzymes are the main mechanisms of the antioxidant effect of the introduced resource in this study.

Sturge-Weber Syndrome (SWS) is among the neurocutaneous diseases, which has several clinical manifestations of ocular (glaucoma), cutaneous (port-wine stain), neurological (seizures) and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for the SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against this syndrome. Development of such platforms of bioassay can bring along the implementation of high throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of biological targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholine esterase, alkaline phosphatase, gamma-aminobutyricacidergic, Hypoxia-Inducible Factor (HIF) -1α and 2α are suggested. This article is protected by copyright. All rights reserved.

The Myxococcales order consist of eleven families comprising30 genera, and are featured by the formation of the highest level of differential structure aggregations called fruiting bodies. These multicellular structures are essential for their resistance in ecosystems and is used in the primitive identification of these bacteria while their accurate taxonomic position is confirmed by the nucleotide sequence of 16SrRNA gene. Phenotypic classification of these structures is currently performed based on the stereomicroscopic observations that demand personal experience. The detailed phenotypic features of the genera with similar fruiting bodies are not readily distinctive by not particularly experienced researchers. The human examination of the fruiting bodies requires high skill and is error-prone. An image pattern analysis of schematic images of these structures conducted us to the construction of a database, which led to an extractable recognition of the unknown fruiting bodies. In this paper, Convolutional Neural Network (CNN) was considered as a baseline for recognition of fruiting bodies. In addition, to enhance the result the classifier, part of CNN is replaced with other classifiers. By employing the introduced model, all 30 genera of this order could be recognized based on stereomicroscopic images of the fruiting bodies at the genus level that not only does not urge us to amplify and sequence gene but also can be attained without preparation of microscopic slides of the vegetative cells or myxospores. The accuracy of 77.24% in recognition of genera and accuracy of 88.92% in recognition of suborders illustrate the applicability property of the proposed machine learning model.

Deep learning (DL) algorithms are a subset of machine learning algorithms with the aim of modeling complex mapping between a set of elements and their classes. In parallel to the advance in revealing the molecular bases of diseases, a notable innovation has been undertaken to apply DL in data/libraries management, reaction optimizations, differentiating uncertainties, molecule constructions, creating metrics from qualitative results, and prediction of structures or interactions. From source identification to lead discovery and medicinal chemistry of the drug candidate, drug delivery, and modification, the challenges can be subjected to artificial intelligence algorithms to aid in the generation and interpretation of data. Discovery and design approach, both demand automation, large data management and data fusion by the advance in high-throughput mode. The application of DL can accelerate the exploration of drug mechanisms, finding novel indications for existing drugs (drug repositioning), drug development, and preclinical and clinical studies. The impact of DL in the workflow of drug discovery, design, and their complementary tools are highlighted in this review. Additionally, the type of DL algorithms used for this purpose, and their pros and cons along with the dominant directions of future research are presented.

The spores of Bacillus atrophaeus are used to monitor the efficacy of disinfection and sterilization processes, particularly in dry heat and ethylene oxide sterilization processes. The production process of biological sterilization indicators of this bacterium includes bacterial sporulation, which leads to a dormant structure with extreme resistance to heat stresses. In this study, the efficacy of the application of nanomaterials as alternative carriers instead of regular paper strips in the recovery of spores and the stability of the prepared bioindicator was investigated. For this purpose, the structural types of nanomaterials applied as carriers on D values and spore absorption were evaluated and compared. The results suggest the nanomaterial’s potential to be used as the supports of bioindicators. Among the evaluated nanomaterials adsorbents, including nanocellulose, lignocellulose, chitin, gamma alumina and silica, silica and gamma alumina illustrated the highest spore absorption potency (107 CFU/mL) and highest spore resistance by the D value of 6.5 min. The results of this study suggest that nanomaterials can be a suitable replacement for conventional strips due to their higher perdurability.

The emergence and prevalence of multi-drug-resistant bacterial strains increase the potential for outbreaks of incurable infections. The discovery of novel antibiotics and pharmacological preparations requires the identification of novel bioactive small molecules. A specific, sensitive, and reliable quantification method using high-performance liquid chromatography (HPLC) with UV detection was developed for the determination of total persipeptides (A and B), which are cyclic pentapeptides found in the fermentation broth of Streptomyces zagrosensis UTMC 1154 that exhibit bioactivity against methicillin-resistant Staphylococcus aureus (MRSA). A simple liquid–liquid extraction (LLE) method using butanol was employed to extract persipeptides from the fermentation broth prior to HPLC analysis. The chromatographic separation of persipeptides and the internal standard, virginiamycin, was achieved with a gradient of acetonitrile and water on a C18 reversed-phase analytical column in a 25-min analytical run utilizing a flow rate of 0.8 mL min−1 and detection at 210 nm. The whole assay was validated, and the method presented a linear response range with a regression coefficient of determination R 2 of 0.9996 for the quantification of persipeptides in the concentration range of 3.9–250.0 µg mL−1, as well as extraction recoveries ranging from 54.78 ± 9.83 % to 56.45 ± 16.33 %. The bias and the precision of the proposed method were

Plant growth-promoting bacteria (PGPB) include bacteria that colonize the plant and improve the growth directly by providing growth factors or indirectly by protection against environmental stress. PGPB have the potential to cooperate to the alleviation of drought stress which is among the most critical stress for plants. These beneficial microorganisms convey drought tolerance through the production of exopolysaccharides (EPS), phytohormones, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and volatile compounds, inducing accumulation of osmolytes and antioxidants, regulation of stress-responsive genes, induction of systemic tolerance, and modification of root morphology toward the adaptation to drought tolerance.