Cannabinoids' Role in Modulating Central and Peripheral Immunity in Neurodegenerative Diseases.

Cannabinoids (the endocannabinoids, the synthetic cannabinoids, and the phytocannabinoids) are well known for their various pharmacological properties, including neuroprotective and anti-inflammatory features, which are fundamentally important for the treatment of neurodegenerative diseases. The aging of the global population is causing an increase in these diseases that require the development of effective drugs to be even more urgent. Taking into account the unavailability of effective drugs for neurodegenerative diseases, it seems appropriate to consider the role of cannabinoids in the treatment of these diseases. To our knowledge, few reviews are devoted to cannabinoids' impact on modulating central and peripheral immunity in neurodegenerative diseases. The objective of this review is to provide the best possible information about the cannabinoid receptors and immuno-modulation features, peripheral immune modulation by cannabinoids, cannabinoid-based therapies for the treatment of neurological disorders, and the future development prospects of making cannabinoids versatile tools in the pursuit of effective drugs.

Cannabis as a Source of Approved Drugs: A New Look at an Old Problem.

Cannabis plants have been used in medicine since ancient times. They are well known for their anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, anti-microbial, anti-viral, and anti-fungal activities. A growing body of evidence indicates that targeting the endocannabinoid system and various other receptors with cannabinoid compounds holds great promise for addressing multiple medical conditions. There are two distinct avenues in the development of cannabinoid-based drugs. The first involves creating treatments directly based on the components of the cannabis plant. The second involves a singular molecule strategy, in which specific phytocannabinoids or newly discovered cannabinoids with therapeutic promise are pinpointed and synthesized for future pharmaceutical development and validation. Although the therapeutic potential of cannabis is enormous, few cannabis-related approved drugs exist, and this avenue warrants further investigation. With this in mind, we review here the medicinal properties of cannabis, its phytochemicals, approved drugs of natural and synthetic origin, pitfalls on the way to the widespread clinical use of cannabis, and additional applications of cannabis-related products.

Medicinal Properties of Anchusa strigosa and Its Active Compounds.

Anchusa strigosa is a widespread weed in Greece, Syria, Turkey, Lebanon, Israel, Jordan, and Iran. The purpose of this study was to identify the phytochemicals of Anchusa strigose and estimate the pro-wound healing (pro-WH) and antimicrobial activities of its active compounds. An identification of volatile compounds was performed by GC/MS analysis; HPLC, LC-ESI-MS, and MALDI-TOF-MS were also applied. Our results demonstrate that two specific combinations of compounds from A. strigosa extract significantly enhanced WH (p < 0.001). Several flavonoids of the plant extract, including quercetin 3-O-rutinoside, kaempferol, kaempferol 3-O-ß-rhamnopyranosyl(1→6)-ß-glucopyranoside, and kaempferol 3-O-α-rhamnopyranosyl(1→6)-ß-galactopyranoside, were effective against drug-resistant microorganisms. In addition, all the above-mentioned compounds had antibiofilm activity against Escherichia coli and Salmonella enteritidis.

Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny.

BACKGROUND: Antimicrobial resistance (AMR) in Helicobacter pylori is increasing globally and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to conduct an analysis of the H. pylori resistome and phylogeny. MATERIALS/METHODS: A total of 1040 H. pylori isolate sequences were retrieved. Analysis was conducted via an in-house bioinformatics pipeline targeting point mutations in selected genes frequently associated with AMR (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) and phylogenomic analyses using core genome multilocus sequence typing (cgMLST). RESULTS: Phylogenomic analysis revealed a notable geographical clustering of H. pylori genomes across world regions, but large distances of more than 1000 loci between isolates on individual branches were observed. Resistome analysis revealed the prevalence of common mutations which have previously been found to correlate with phenotypic antibiotic resistance; the most common point mutations for each gene were S589G (pbp1A, 48.8% of perfect aligned sequences), A2143G (23S rRNA, 27.4% of perfectly aligned sequences), N87 K\I\Y (gyrA, 14.7% of perfectly aligned sequences), R131K (rdxA, 65.7% of perfectly aligned sequences), and C193S (frxA, 62.6% of perfectly aligned sequences). CONCLUSIONS: This is the largest study to date featuring the global phylogeny of H. pylori in conjunction with a global snapshot of the H. pylori resistome based on >1000 genomes. Further analyses that combine WGS and phenotypic methods will provide further understanding of the association between the mutations and resistance.

Comparing the Antimicrobial Effect of Silver Ion-Coated Silicone and Gentamicin-Irrigated Silicone Sheets from Breast Implant Material.

BACKGROUND: Post-operative infection is a significant complication of breast implant surgery that may require extensive use of antibiotics and surgical interventions. Here, we developed a biomaterial coating that is chemically bonded to silicone implants which delivers antimicrobial ions over time. METHODS: After coating the silicone implants with a "mediator" polymer (γ-PGA), the implants were impregnated with silver (Ag) ions. Antimicrobial effects of these implants were assayed with modified Kirby-Bauer disk diffusion method. The silicone disks were transferred to a plate with fresh bacteria. Control was intended to simulate an intra-operative wash. RESULTS: The Ag-γ-PGA coated silicone demonstrated antimicrobial effects against the most common etiological agents of breast implant infections, including Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Klebsiella pneumoniae. There was no effect of inhibition of bacterial growth around the control silicone or the silicone coated only with γ-PGA. The zone of inhibition was generally larger around the Ag-γ-PGA coated silicone as compared to the silicone irrigated with gentamicin, and continued antibacterial effect was also observed at 48 hours in the Ag-γ-PGA coated silicone for all bacteria groups with the exception of P. aeruginosa. Gentamicin-irrigated silicone did not inhibit bacterial growth at 48 hours. CONCLUSION: The observed antibacterial performance of the Ag-γ-PGA coating as compared to simulated intra-operative antibiotic wash is promising and should be further evaluated to develop the next generation of implants with diminished risk for post-operative implant infections.

Serine protease inhibitors interact with IFN-γ through up-regulation of FasR; a novel therapeutic strategy against cancer.

Among the many immunomodulatory and anti-tumor activities, IFN-γ up-regulates tumor cell death mediated by Fas receptor (FasR). Our and several other studies have demonstrated the involvement of trypsin-like proteases (TLPs) in the mode of action of IFN-γ. In the present study, we tried to unravel the role of serine proteases in IFN-γ induced Fas-mediated cell death. Our present results show that both tosyl-l-Lysine chloromethylketone (TLCK), a trypsin like protease inhibitor and tosyl-l-phenylalanine chloromethylketone (TPCK) - a chymotrypsin like protease (CLP) inhibitor, sensitize HeLa cells to Fas-mediated cell death. The combined effect of these protease inhibitors with anti-Fas was stronger than additive. In contrast, elastase inhibitor III (EI), which also contains the chloromethyl ketone moiety, was not active. Furthermore, co-addition of TLCK or TPCK with IFN-γ markedly enhanced Fas-induced cell death. IFN-γ led to up-regulation of FasR on its own, which was further enhanced by the co-addition of TLCK or TPCK. This was evident both by increased expression of Fas receptor on cell surface and by elevated Fas mRNA level. This study may provide the basis for the design of a novel combinatory therapeutic strategy that could enhance the eradication of tumors.

Regulation of autophagy by α1-antitrypsin: "a foe of a foe is a friend".

Autophagy is involved in both the cell protective and the cell death process but its mechanism is largely unknown. The present work unravels a novel intracellular mechanism by which the serpin α1-antitrypsin (AAT) acts as a novel negative regulator of autophagic cell death. For the first time, the role of intracellularly synthesized AAT, other than in liver cells, is demonstrated. Autophagic cell death was induced by N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and tamoxifen. By utilizing a fluorescently tagged TPCK analog, AAT was "fished out" (pulled out) as a TPCK intracellular protein target. The interaction was further verified by competition binding experiments. Both inducers caused downregulation of AAT expression associated with activation of trypsin-like proteases. Furthermore, silencing AAT by siRNA induced autophagic cell death. Moreover, AAT administration to cultured cells prevented autophagic cell death. This new mechanism could have implications in the treatment of diseases by the regulation of AAT levels in which autophagy has a detrimental function. Furthermore, the results imply that the high synthesis of endogenous AAT by cancer cells could provide a novel resistance mechanism of cancer against autophagic cell death.

Hybrid Hydrogels of FKF-Peptide Assemblies and Gelatin for Sustained Antimicrobial Activity.

The growing resistance of pathogenic bacteria to conventional antibiotics promotes the development of new antimicrobial agents, including peptides. Hydrogels composed of antimicrobial peptides (AMPs) may be applied as topical treatments for skin infection and wound regeneration. The unique antimicrobial and ultrashort-peptide FKF (Phe-Lys-Phe) was recently demonstrated to form bactericidal hydrogels. Here, we sought to improve the cyto-biocompatibility of FKF by combining FKF hydrogels with gelatin. Homogeneous hybrid hydrogels of FKF:gelatin were developed based on a series of self-assembly steps that involved mixing solutions of the two components with no covalent cross-linkers. The hydrogels were characterized for their structural features, dissolution, cyto-biocompatibility, and antibacterial properties. These hybrid hydrogels first release the antibacterial FKF assemblies, leaving the gelatinous fraction of the hydrogel to serve as a scaffold for tissue regeneration. Sponges of these hybrid hydrogels, obtained by lyophilization and rehydrated prior to application, exhibited enhanced antimicrobial activity compared to the hydrogels' formulations.

Antimicrobial and Antiviral Compounds of Phlomis viscosa Poiret.

Phlomis viscosa Poiret (an evergreen shrub) represents a valuable source of medicinal compounds. In this study, we discovered compounds with antimicrobial and antiviral properties. The aim of this study was to identify compounds of P. viscosa and estimate the antimicrobial and antiviral activity of its phytochemicals. The volatile compounds were identified using gas chromatography/mass spectrometry (GC/MS) analysis. For the identification of nonvolatile components of the extracts, high-performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) were applied. Quercetin 3-O-rutinoside and hesperidin caused a significant decrease in the bacterial concentration of Agrobacterium tumefaciens, Xylella fastidiosa and Pseudomonas syringae (p < 0.001). The growth of drug-resistant microorganisms (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens and Salmonella enteritidis) was inhibited by quercetin 3-O-rutinoside, quercetin 3-O-arabinoside and hesperidin. In addition, these compounds demonstrated antiquorum-sensing properties. Diosmin, hesperidin and quercetin 3-O-arabinoside significantly inhibited varicella zoster virus (VZV) (p < 0.001). Quercetin 3-O-rutinoside and quercetin 3-O-arabinoside were effective against herpes simplex virus 1 (HSV-1), including mutant strains.

Fecal microbiota of the synanthropic golden jackal (Canis aureus).

The golden jackal (Canis aureus), is a medium canid carnivore widespread throughout the Mediterranean region and expanding into Europe. This species thrives near human settlements and is implicated in zoonoses such as rabies. This study explores for the first time, the golden jackal fecal microbiota. We analyzed 111 fecal samples of wild golden jackals using 16S rRNA amplicon sequencing the connection of the microbiome to animal characteristics, burden of pathogens and geographic and climate characteristics. We further compared the fecal microbiota of the golden jackal to the black-backed jackal and domestic dog. We found that the golden jackal fecal microbiota is dominated by the phyla Bacteroidota, Fusobacteriota and Firmicutes. The golden jackal fecal microbiota was associated with different variables, including geographic region, age-class, exposure to rabies oral vaccine, fecal parasites and toxoplasmosis. A remarkable variation in the relative abundance of different taxa was also found associated with different variables, such as age-class. Linear discriminant analysis effect size (LEfSe) analysis found abundance of specific taxons in each region, Megasphaera genus in group 1, Megamonas genus in group 2 and Bacteroides coprocola species in group 3. We also found a different composition between the fecal microbiota of the golden jackal, blacked-backed jackal and the domestic dog. Furthermore, LEfSe analysis found abundance of Fusobacterium and Bacteroides genera in the golden jackal, Clostridia class in blacked-backed jackal and Megamonas genus in domestic dog. The golden jackal fecal microbiota is influenced by multiple factors including host traits and pathogen burden. The characterization of the microbiota of this thriving species may aid in mapping its spread and proximity to human settlements. Moreover, understanding the jackal microbiota could inform the study of potential animal and human health risks and inform control measures.

Long-Read Sequencing and Hybrid Assembly for Genomic Analysis of Clinical Brucella melitensis Isolates.

Brucella melitensis is a key etiological agent of brucellosis and has been increasingly subject to characterization using sequencing methodologies. This study aimed to investigate and compare short-read, long-read, and hybrid assemblies of B. melitensis. Eighteen B. melitensis isolates from Southern Israel were sequenced using Illumina and the Oxford Nanopore (ONP) MinION, and hybrid assemblies were generated with ONP long reads scaffolded on Illumina short reads. Short reads were assembled with INNUca with SPADes, long reads and hybrid with dragonflye. Abricate with the virulence factor database (VFDB) and in silico PCR (for the genes BetB, BPE275, BSPB, manA, mviN, omp19, perA, PrpA, VceC, and ureI) were used for identifying virulence genes, and a total of 61 virulence genes were identified in short-read, long-read, and hybrid assemblies of all 18 isolates. The phylogenetic analysis using long-read assemblies revealed several inconsistencies in cluster assignment as compared to using hybrid and short-read assemblies. Overall, hybrid assembly provided the most comprehensive data, and stand-alone short-read sequencing provided comparable data to stand-alone long-read sequencing regarding virulence genes. For genomic epidemiology studies, stand-alone ONP sequencing may require further refinement in order to be useful in endemic settings.

Fecal Microbiome Features Associated with Extended-Spectrum ß-Lactamase-Producing Enterobacterales Carriage in Dairy Heifers.

Extended-spectrum ß-lactamases (ESBLs) are a growing public health threat, and one key human exposure point is through livestock and the food supply. Understanding microbiome factors associated with fecal ESBL carriage can help detect and ideally assist with controlling and preventing ESBL dissemination among livestock. The objective of this study was to investigate the diversity and composition of the heifer fecal microbiota in ESBL-producing Enterobacterales (ESBL-PE) carriers and noncarriers. A total of 59 fecal samples were collected from replacement heifers between 12 and 18 months old from eight dairy farms in central Israel. Genomic DNA was extracted, and 16S rRNA amplicon sequencing was performed (Illumina short reads), focusing on a comparison between 33 ESBL-PE carriers (55.9%) and 26 (44.1%) noncarriers. Samples were analyzed and compared using QIIME2 (DADA2 pipeline and taxonomic assignment with SILVA database) and associated R packages for alpha and beta diversity and taxonomic abundances. Alpha diversity (Shannon diversity) and beta diversity (unweighted UniFrac) showed no significant difference between ESBL-PE carriers and noncarriers. Heifers from farms feeding calves with pooled colostrum had higher ESBL-PE carriage rates than heifers from farms feeding with individual mother colostrum (p < 0.001). Taxonomical abundance analysis revealed that the most common bacterial phyla were Bacteroidetes (44%) and Firmicutes (38%). There was no significant difference in taxonomic composition between ESBL-PE carriers and noncarriers at the phylum and genus levels. However, LEfSe biomarker discovery analysis identified several genera which were significantly different between carriers and noncarriers. For example, Prevotellacaea, Bacteroides, Rikenellaceae, and uncultured Bacteroidales were more abundant in ESBL carriers than noncarriers. Some aspects of microbiota composition differ between ESBL carriers and noncarriers in dairy heifers, specifically the abundance of certain genera. Feeding with pooled colostrum may play a role in that assembly. These could potentially serve as markers of ESBL-PE carriage. However, further research is needed to determine whether these observed differences have a significant impact on colonization with ESBL-PE.

Genomic Epidemiology of Clinical Brucella melitensis Isolates from Southern Israel.

Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of B. melitensis in this region has not yet been elucidated. A cohort of brucellosis cases (n = 118) diagnosed between 2017-2019 was studied using whole-genome sequencing (WGS). Phylogenetic analyses utilized core genome MLST (cgMLST) for all local isolates and core genome SNPs for 347 human-associated B. melitensis genomes, including Israeli and publicly available sequences. Israeli isolates formed two main clusters, presenting a notable diversity, with no clear dominance of a specific strain. On a global scale, the Israeli genomes clustered according to their geographical location, in proximity to genomes originating from the Middle East, and formed the largest cluster in the tree, suggesting relatively high conservation. Our study unveils the genomic epidemiology of B. melitensis in Southern Israel, implicating that rather than a common source, the transmission pattern of brucellosis among Bedouin communities is complex, predominantly local, and household-based. Further, genomic surveillance of B. melitensis is expected to inform future public health and veterinary interventions and clinical care.

The Effects of One Anastomosis Gastric Bypass Surgery on the Gastrointestinal Tract.

One anastomosis gastric bypass (OAGB) is an emerging bariatric procedure, yet data on its effect on the gastrointestinal tract are lacking. This study sought to evaluate the incidence of small-intestinal bacterial overgrowth (SIBO) following OAGB; explore its effect on nutritional, gastrointestinal, and weight outcomes; and assess post-OABG occurrence of pancreatic exocrine insufficiency (PEI) and altered gut microbiota composition. A prospective pilot cohort study of patients who underwent primary-OAGB surgery is here reported. The pre-surgical and 6-months-post-surgery measurements included anthropometrics, glucose breath-tests, biochemical tests, gastrointestinal symptoms, quality-of-life, dietary intake, and fecal sample collection. Thirty-two patients (50% females, 44.5 ± 12.3 years) participated in this study, and 29 attended the 6-month follow-up visit. The mean excess weight loss at 6 months post-OAGB was 67.8 ± 21.2%. The glucose breath-test was negative in all pre-surgery and positive in 37.0% at 6 months (p = 0.004). Positive glucose breath-test was associated with lower reported dietary intake and folate levels and higher vitamin A deficiency rates (p ≤ 0.036). Fecal elastase-1 test (FE1) was negative for all pre-surgery and positive in 26.1% at 6 months (p = 0.500). Both alpha and beta diversity decreased at 6 months post-surgery compared to pre-surgery (p ≤ 0.026). Relatively high incidences of SIBO and PEI were observed at 6 months post-OAGB, which may explain some gastrointestinal symptoms and nutritional deficiencies.

Prevalence and Characteristics of Carriage of Neisseria meningitidis Among Young Israeli Adults.

Background: No updated data currently exist regarding Neisseria meningitidis carriage and genomic epidemiology among young Israeli adults. Methods: Oropharyngeal swabs were collected from 1801 military recruits on the day of recruitment during 2019. Neisseria meningitidis was detected and identified by culture and quantitative polymerase chain reaction (qPCR). Confirmed isolates were serotyped by qPCR, and encapsulated strains underwent whole-genome sequencing. Risk factors for carriage were determined by analyzing focused questionnaires using uni- and multivariate models. Genomic typing was performed by means of core genome multilocus sequence typing. Results: Carriage rates overall and of encapsulated strains were 20.1% and 6.7%, respectively. Genogroups B (49.2%) and Y (26.7%) were the most commonly encapsulated strains. Genogroups C, W, and X were scarce, and genogroup A was absent. The most notable clonal complexes (CCs) were CC23 (n = 30), CC32 (n = 16), and CC44/41 (n = 9). Carriage was significantly associated with smoking (odds ratio [OR], 1.82; 95% CI, 1.43-2.33) and boarding school attendance before recruitment (OR, 1.49; 95% CI, 1.14-1.96). Conclusions: The prevalence of meningococcal carriage among young Israeli adults is high, compared with similar studies in other developed countries. This might be due to sociocultural characteristics including smoking and boarding school attendance during and after high school. The dominant genogroups and CCs found were compatible with those implicated in invasive disease in Israel.

Targeting Necrosis: Elastase-like Protease Inhibitors Curtail Necrotic Cell Death Both In Vitro and in Three In Vivo Disease Models.

Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical approaches, enzymatic assays, medicinal chemistry, and siRNA library screening. These findings provide strategies to treat and prevent necrosis, including known medicines used for other indications, siRNAs, and establish a platform for the design of new inhibitory molecules. Indeed, inhibitors of these pathways demonstrated protective activity in vitro and in vivo in animal models of traumatic brain injury, acute myocardial infarction, and drug-induced liver toxicity. Consequently, this study may pave the way for the development of novel therapies for the treatment, inhibition, or prevention of a large number of hitherto untreatable diseases.

Medicinal Properties of Lilium candidum L. and Its Phytochemicals.

Lilium candidum L., known as Madonna, meadow, or white lily, is a bulbous plant from the Liliaceae family, originating in the Middle East. L. candidum has been abundantly used in folk medicine since ancient times to relieve a variety of ailments, including age-related diseases, burns, ulcers, and coughs. The aim of this article is to investigate the anti-inflammatory and anti-diabetic activities of L. candidum extracts and its active phytochemicals. Some active volatile phytochemicals were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Significant (p < 0.001) anti-diabetic properties of the extracts kaempferol, linalool, citronellal, and humulene were demonstrated by an elevation in glucose uptake by adipocytes. The significant (p < 0.01) effect of the plant extracts kaempferol, citronellal, and humulene on the secretion of pro-inflammatory cytokines interleukin 6 (IL-6) and interleukin 8 (IL-8) was demonstrated using enzyme-linked immunosorbent assay. Altogether, L. candidum and its rich collection of phytochemicals hold promising medicinal potential, and further investigations of its therapeutic prospects are encouraged.

Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori.

Antimicrobial resistance (AMR) in Helicobacter pylori is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the H. pylori resistome and phylogeny in order to characterize Israeli H. pylori. Israeli H. pylori isolates (n = 48) underwent antimicrobial susceptibility testing (AST) against five antimicrobials and WGS analysis. Literature review identified 111 mutations reported to correlate with phenotypic resistance to these antimicrobials. Analysis was conducted via our in-house bioinformatics pipeline targeting point mutations in the relevant genes (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) in order to assess genotype-to-phenotype correlation. Resistance rates of study isolates were as follows: clarithromycin 54%, metronidazole 31%, amoxicillin 10%, rifampicin 4%, and levofloxacin 2%. Genotype-to-phenotype correlation was inconsistent; for every analyzed gene at least one phenotypically susceptible isolate was found to have a mutation previously associated with resistance. This was also observed regarding mutations commonly used in commercial kits to diagnose AMR in H. pylori cases. Furthermore, 11 novel point mutations associated with a resistant phenotype were detected. Analysis of a unique set of H. pylori isolates demonstrates that inferring resistance phenotypes from WGS in H. pylori remains challenging and should be optimized further.

Genomic Characterization of Antimicrobial Resistance, Virulence, and Phylogeny of the Genus Ochrobactrum.

Ochrobactrum is a ubiquitous Gram-negative microorganism, mostly found in the environment, which can cause opportunistic infections in humans. It is almost uniformly resistant to penicillins and cephalosporins through an AmpC-like ß-lactamase enzyme class (OCH). We studied 130 assembled genomes, of which 5 were animal-derived isolates recovered in Israel, and 125 publicly available genomes. Our analysis focused on antimicrobial resistance (AMR) genes, virulence genes, and whole-genome phylogeny. We found that 76% of Ochrobactrum genomes harbored a blaOCH ß-lactamase gene variant, while 7% harbored another AmpC-like gene. No virulence genes other than lipopolysaccharide-associated genes were found. Core genome multilocus sequence typing clustered most samples to known species, but neither geographical clustering nor isolation source clustering were evident. When analyzing the distribution of different blaOCH variants as well as of the blaOCH-deficient samples, a clear phylogenomic clustering was apparent for specific species. The current analysis of the largest collection to date of Ochrobactrum genomes sheds light on the resistome, virulome, phylogeny, and species classification of this increasingly reported human pathogen. Our findings also suggest that Ochrobactrum deserves further characterization to underpin its evolution, taxonomy, and antimicrobial resistance.

Effect of Bioactive Phytochemicals from Phlomis viscosa Poiret on Wound Healing.

Phlomis viscosa Poiret is an evergreen shrub growing in Israel, Turkey, Lebanon, and Syria with acknowledged pro-wound healing (WH) properties. In this study, we evaluated the pro-WH potential of selected compounds found in this plant. Among the pro-WH compounds (identified by us) was a combination of three chemicals-diosmin, 1-octen-3-ol, and himachala-2,4-diene which enhanced WH significantly both in in vitro and in vivo models. The determined phytochemicals combination could be used for the treatment of chronic wounds. The effect of the extracts, diosmin, 1-octen-3-ol on the secretion of pro-inflammatory cytokines, IL-6 (A) and IL-8 (B) by human dermal fibroblasts was significant (p < 0.001). In addition, the beneficial effect of extracts of P. viscosa and its phytochemicals on WH was evidenced by inhibiting the growth of several WH delaying microorganisms.