Search

Diabetes is one of the four major non-communicable diseases, and appointed by the world health organization as the seventh leading cause of death worldwide. The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes. The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes, assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation. On a parallel basis, microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment, all of which can be reversed by antimicrobial treatment. Standing at the crossroads between diabetes, immunity and infection, we aim in this review at projecting the interplay between immunity and diabetes, shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents. Furthermore, we focused on the anti-diabetic drugs that can confer antimicrobial or anti-virulence activities.

Candida albicans is the most common human fungal pathogen that has developed extensive virulence factors which allows successful colonization and infection of the host. Anti-virulence agents can alleviate the pathogenesis of fungi and help the immune system to eradicate them easily. This study aimed to explore the anti-virulence effect of domperidone and candesartan against C. albicans standard strain. Sub-inhibitory concentrations (1/4 and 1/8 of minimum inhibitory concentration) of domperidone and candesartan significantly inhibited the virulence factors hemolysin, lipase, protease, phospholipase, and bioflim formation. It was found that candesartan inhibited biofilm formation by 60.48–67.91%, hemolysin activity (61.21–74.14%), phospholipase activity (40–49.67%), lipase activity (58.97–73%), and protease activity (52.63%), while domperidone was found to inhibit biofilm formation by 70.54–77.49%, hemolysin activity (64.84–69.84%), phospholipase activity (49.67–60%), lipase activity (50–54.87%), and protease activity (52.63–57.9%). Quantitative real time-PCR confirmed the anti-virulence activity of domperidone and candesartan as both drugs significantly reduce the expression of the virulence genes SAP2, SAP6, PLB1, PLB2, LIP4, LIP5. In conclusion, domperidone and candesartan could serve as anti-virulence agents for treatment of C. albicans infections.

AIM: The present study was designed to investigate use of intraoral radiographic techniques (conventional and digital) among general dental practitioners (GDP) in Saudi Arabia with focus on its availability in workplace, ease of the technique, and the recommended technique to be taught during undergraduate based on individual experience. METHODS: A questioner in form of a Google sheet was designed concerning demographic data, country, district, university, year of graduation, availability of radiographic technique available in workplace, which technique learned during undergraduate study, and which technique should teach during undergraduate study based on individual experience. A GDP list was developed from different dental groups on social media. The questioner was sent to the GDP list and to improve the response rate, telephone calls were made in advance to all expected participants. RESULTS: About 62.2% of participants were graduated within past 5 years, the most common dental X-ray processing technique learned during undergraduate study was the digital and conventional (both theoretical and practical) in 47.6% of participants followed by conventional (theoretical and practical) technique in 21% participants. Based on their work experience, 74.8% of participants preferred both digital and conventional techniques should be taught in dental Saudi Universities/Colleges while, the digital method was preferred by 21%. CONCLUSION: However, intraoral digital radiographic technique is widely available in most regions in Saudi Arabia; it is recommended to teach both intraoral digital and conventional radiographic techniques during undergraduate study.

Mahmoud Youns, 1, 2 Momen Askoura, 3 Hisham A Abbas, 3 Gouda H Attia, 4, 5 Ahdab N Khayyat, 6 Reham M Goda, 7 Ahmad J Almalki, 6 El-Sayed Khafagy, 8, 9 Wael AH Hegazy 3 1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo, Egypt; 2Department of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany; 3Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 4Department of Pharmacognosy, Faculty of Pharmacy, Kafr El-Shiekh University, Kafr El-Shiekh, Egypt; 5Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 7Department of Microbiology and Biotechnology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Mansoura, Egypt; 8Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj, 11942, Saudi Arabia; 9Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia, 41552, EgyptCorrespondence: Mahmoud Youns Tel +0096891742704Email dr.mahmoudyouns@yahoo.comBackground: Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant.Purpose: To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression.Methods: The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer.Results: Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3, and down-expression of RRM2 and MCM4.Conclusion: The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth.Keywords: celastrol, natural products, pancreatic cancer, RRM2, DDIT3, MCM4

Background: Infections affecting neonates caused by Staphylococcus aureus are widespread in healthcare facilities; hence, novel strategies are needed to fight this pathogen. Targeting virulence factors necessary to induce host damage and disease is a new tactic for antimicrobial therapy with several benefits which could lead to decreased resistance. The effect of FDA-approved drugs (sodium bicarbonate, dexamethasone, and ascorbic acid) with sub-inhibitory concentration (1/8 MIC) was evaluated for their capability to hinder virulence factors production in Staphylococcus aureus phenotypically. Furthermore, their effects were estimated genotypically using qRT‑PCR.Results: Sub-inhibitory concentrations (1/8 MIC) of sodium bicarbonate, dexamethasone, and ascorbic acid reduced the production of Staphylococcus aureus virulence factors, including biofilm formation, staphyloxanthin, proteases, and hemolysin production, as well as resistance to oxidative stress. At the molecular level, qRT-PCR was used to assess the relative expression levels of CrtM, SigB, SarA, AgrA, hla, fnbA, and icaA genes regulating virulence factors production and showed a significant reduction in the relative expression levels of all the tested genes. Conclusions: In summary, the current findings reveal that sodium bicarbonate, dexamethasone, and ascorbic acid have strong anti-virulence effects against multi-drug resistant Staphylococcus aureus. Thus, suggesting the use of sodium bicarbonate, dexamethasone, and ascorbic acid for fighting Staphylococcus aureus, and also suggesting that they might be used to treat infections caused by multi-drug resistant Staphylococcus aureus in place of or in addition to conventional antimicrobials.

Background: Staphylococcus aureus is a common hospital acquired infections pathogen. Multidrug-resistant Methicillin-resist- ant Staphylococcus aureus represents a major problem in Egyptian hospitals. The over-expression of efflux pumps is a main cause of multidrug resistance. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. This study aimed to investigate the role of efflux pumps in multidrug resistance. Methods: Twenty multidrug resistant S. aureus isolates were selected. Efflux pumps were screened by ethidium bromide agar cartwheel method and polymerase chain reaction. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilu- tion method. Results: Seventy percent of isolates showed strong efflux activity, while 30% showed intermediate activity. The efflux genes mdeA, norB, norC, norA and sepA were found to play the major role in efflux, while genes mepA, smr and qacA/B had a minor role. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. Conclusion: Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials. Keywords: Staphylococcus aureus; multidrug resistance; efflux pump inhibitors.

Long-term antibiotic treatment results in the spread of multi-drug resistance in Pseudomonas aeruginosa that complicates treatment. Anti-virulence agents can be viewed as alternative options that cripple virulence factors of the bacteria to facilitate their elimination by the host immunity. The use of nanoparticles in the inhibition of P. aeruginosa virulence factors is a promising strategy. This study aims to study the effect of metformin (MET), metformin nano emulsions (MET-NEs), silver metformin nano emulsions (Ag-MET-NEs) and silver nanoparticles (AgNPs) on P. aeruginosa virulence factors’ expression. The phenotypic results showed that MET-NEs had the highest virulence inhibitory activity. However, concerning RT-PCR results, all tested agents significantly decreased the expression of quorum sensing regulatory genes of P. aeruginosa; lasR, lasI, pqsA, fliC, exoS and pslA, with Ag-MET-NEs being the most potent one, however, it failed to protect mice from P. aeruginosa pathogenesis. MET-NEs showed the highest protective activity against pseudomonal infection in vivo. Our findings support the promising use of nano formulations particularly Ag-MET-NEs as an alternative against multidrug resistant pseudomonal infections via inhibition of virulence factors and quorum sensing gene expression.

Biofilms facilitate the pathogenesis of life-threatening

Serratia marcescens is an emerging opportunistic bacterium that can cause healthcare-associated infections. The high rate of multidrug resistance and the ability to produce a set of virulence factors, by which it can produce infectious diseases makes it urgent to find an alternative approach to the treatment of such infections. Disarming of virulence by targeting of quorum sensing (QS) as the regulating mechanism of virulence is a promising approach that has no effect on bacterial growth that is considered a key factor in emergence of resistance. This study was designed to investigate the ability of sub-inhibitory concentrations (sub-MICs) of sotolon to attenuate virulence of a clinical isolate of S. marcescens. Sotolon at 25 and 50 μg/ml inhibited 35.2 and 47.5% of biofilm formation, respectively. The inhibition of swimming motility were 41.4 and 69.3%, while that of swarming motility were 77.6 and 86.8% at 25 and 50 µg/ml, respectively. Moreover, sotolon reduced prodigiosin production by 76.6 and 87.6% at concentrations of 25 and 50 µg/ml, respectively. Protease activity was reduced by 25 µg/ml of sotolon by 54.8% and was completely blocked at 50 µg/ml. The relative expression of genes regulating virulence factors decreased by 40% for fimA, 29% for fimC, 59% for flhC, 57% for flhD, 39% for bsmB, 37% for rssB, 49% for rsmA, 54% for pigP, and 62% for shlA gene in the presence of 50 µg/ml sotolon. In conclusion, sotolon is an anti-virulence agent that could be used for the treatment of S.marcescens hospital-acquired infections.

BackgroundInfectious diseases that Enterobacteriaceae cause are spreading on a wide scale. Examples of these infections are gastrointestinal tract infections, meningitis, pneumonia, septicemia, urinary tract infections, and wound infections. Antibiotic resistance among Enterobacteriaceae is a critical problem that makes treatment difficult. Tigecycline is a broad spectrum antibiotic that is effective against multi-drug resistant organisms (MDR) and beneficial in the therapy of infections caused by Enterobacteriaceae.ObjectivesThis study aims to evaluate the in vitro activity of tigecycline against clinical isolates of Enterobacteriaceae species and detect the possible resistance mechanisms of them against β-lactams.MethodsThe sensitivity of different isolates to antibiotics was determined by standard disc diffusion method. Phenotypic detection of resistance mechanisms such as extended spectrum β-lactamase (ESBL), AmpC, ESBL& AmpC co-producers and metallo β-lactamase (MBL) β-lactamases enzymes producer isolates was investigated.ResultsA total of eighty three Enterobacteriaceae clinical isolates were collected. The common bacteria isolated were Escherichia coli and Klebsiella pneumoniae. Multidrug resistance was found in 59.04% of tested isolates. The isolates were resistant to sulphamethaxzole-trimethoprim, ciprofloxacin, tetracycline and impenem. The highest resistance was found to sulphamethaxazole-trimethoprim followed by ciprofloxacin, tetracycline and imipenem. Phenotypic detection of resistance mechanisms revealed that 69.4% of clinical isolates were ESBL producers, 12.2% were AmpC producers, 8.2% were ESBL and AmpC co-producers, while 10.2% were MBL producers. There was no resistance found to tigecycline among all Enterobacteriaceae isolates tested.ConclusionThis study showed that tigecycline has potent in vitro activity against ESBL, AmpC, combined ESBL and AMPC and MBL β-lactamases producing Enterobacteriaceae.

Pseudomonas aeruginosa is an opportunistic pathogen exhibiting higher resistance to commonly used antibiotics. Microbial resistance to antibiotics is a major problem that hinders attempts to control microbial infections. Quorum sensing inhibitors could help us solve such problem by repressing quorum sensing that controls the production of virulence factors in many pathogens including P. aeruginosa. In this study, the influence of tenoxicam, a non-steroidal anti-inflammatory drug, on quorum sensing in P. aeruginosa was characterized. Treatment of P. aeruginosa with tenoxicam decreased production of many virulence factors such as pyoverdin, rhamnolipids, pyocyanin, elastase, proteases, and hemolysins. Moreover, qRT-PCR revealed a significant reduction in expression of quorum sensing genes in tenoxicam-treated P. aeruginosa in comparison with untreated bacteria. Tenoxicam markedly reduced the capacity of P. aeruginosa to kill mice infection model. Mice injected with tenoxicam-treated P. aeruginosa exhibited higher survival rate as compared with those inoculated with untreated bacteria. Current data clearly demonstrate that tenoxicam has quorum sensing inhibitory effect on P. aeruginosa. Tenoxicam could play a role in reduction of Pseudomonas quorum sensing-dependant virulence factors production, and therefore affect its pathogenesis in the host. In summary, the current study suggests that tenoxicam could be used as adjuvant to antibiotics in the management of diseases caused by P. aeruginosa.

Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of S. aureus may generate weaker selection for resistant strains, anti-virulence agents disarm the pathogen instead of killing it. In this study, the ability of the FDA-approved drugs domperidone, candesartan, and miconazole as inhibitors of S. aureus virulence was investigated. The effect of tested drugs was evaluated against biofilm formation, lipase, protease, hemolysin, and staphyloxanthin production by using phenotypic and genotypic methods. At sub-inhibitory concentrations, candesartan, domperidone, and miconazole showed a significant inhibition of hemolysin (75.8-96%), staphyloxanthin (81.2-85%), lipase (50-65%), protease (40-64%), and biofilm formation (71.4-90%). Domperidone and candesartan have similar activity and were more powerful than miconazole against S. aureus virulence. The hemolysins and lipase inhibition were the greatest under the domperidone effect. Candesartan showed a remarkable reduction in staphyloxanthin production. The highest inhibitory effect of proteolytic activity was obtained with domperidone and candesartan. Biofilm was significantly reduced by miconazole. Expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes were significantly reduced under candesartan (68.98-82.7%), domperidone (62.6-77.2%), and miconazole (32.96-52.6%) at sub-MIC concentrations. Candesartan showed the highest inhibition activity against crtM, sigB, sarA, agrA, hla, and icaA expression followed by domperidone then miconazole. Domperidone showed the highest downregulation activity against fnbA gene. In conclusion, candesartan, domperidone, and miconazole could serve as anti-virulence agents for attenuation of S. aureus pathogenicity.

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.

Pseudomonas aeruginosa can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the P. aeruginosa PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled Chromobacterium violaceum CV026 violet pigment violacein and other P. aeruginosa QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of P. aeruginosa and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of P. aeruginosa infection.

Serratia marcescens is an opportunistic pathogen that causes diverse nosocomial infections. S. marcescens has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in S. marcescens by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of S. marcescens. The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole’s protective activity against S. marcescens pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the S. marcescens SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced S. marcescens virulence factor production in vitro and diminished its pathogenesis in mice. The insilico docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by S. marcescens.

Background This randomized clinical trial was designed to evaluate osteogenic potential of Cissus quadrangularis in alveolar distraction to facilitate implant installation. Material and methods Twenty patients with atrophic ridge were treated by alveolar distraction. After completing distractor activation, patients were randomly divided into two equal groups according to administered drug (placebo and Cissus quadrangularis group). After a consolidation period, distractors were removed and implants were inserted. Clinical evaluation was done to assess wound healing, and distractor and implant stability. Histological evaluation was performed at time of implant insertion. Radiographic evaluation was performed to assess bone volume and density after distraction, as well as, density and bone loss around implant. Results Radiographic and histological results showed that bone formation and maturation of study group were faster than that of control group. There was a significant increased bone density in distracted area and around implant in study group than control group. A significant bone loss at end of consolidation period, and around implant at end of the study was reported in control group than study group. Conclusion Cissus quadrangularis administration during the consolidation period is associated with increased osteogenic potential of distracted bone. The histological and radiographic findings of current study proved that Cissus quadrangularis not only enhances rate of new bone formation, but also bone density to withstand the biomechanical requirements of implant placement in a shorter time. Trial registration This study was retrospectively registered on www.ClinicalTrial.gov: NCT04669795-17\12\2020.

Background Staphylococcus aureus is a common hospital acquired infections pathogen. Multidrug-resistant Methicillin-resistant Staphylococcus aureus represents a major problem in Egyptian hospitals. The over-expression of efflux pumps is a main cause of multidrug resistance. The discovery of efflux pump inhibitors may help fight multidrug resistance by sensitizing bacteria to antibiotics. This study aimed to investigate the role of efflux pumps in multidrug resistance. Methods Twenty multidrug resistant S. aureus isolates were selected. Efflux pumps were screened by ethidium bromide agar cartwheel method and polymerase chain reaction. The efflux pump inhibition by seven agents was tested by ethidium bromide agar cartwheel method and the effect on sensitivity to selected antimicrobials was investigated by broth microdilution method. Results Seventy percent of isolates showed strong efflux activity, while 30% showed intermediate activity. The efflux genes mdeA, norB, norC, norA and sepA were found to play the major role in efflux, while genes mepA, smr and qacA/B had a minor role. Verapamil and metformin showed significant efflux inhibition and increased the sensitivity to tested antimicrobials, while vildagliptin, atorvastatin, domperidone, mebeverine and nifuroxazide showed no effect. Conclusion Efflux pumps are involved in multidrug resistance in Staphylococcus aureus. Efflux pump inhibitors could increase the sensitivity to antimicrobials.

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

Serratia marcescens is an opportunistic nosocomial pathogen and causes wound and burn infections. It shows high resistance to antibiotics and its pathogenicity is mediated by an arsenal of virulence factors. Another therapeutic option to such infections is targeting quorum sensing (QS), which controls the expression of different S. marcescens virulence factors. Prevention of QS can deprive S. marcescens from its bacterial virulence without applying stress on the bacterial growth and facilitates the eradication of the bacteria by immunity. The objective of the current study is to explore the antimicrobial and antivirulence activities of xylitol against S. marcescens. Xylitol could inhibit the growth of S. marcescens. Sub-inhibitory concentrations of xylitol could inhibit biofilm formation, reduce prodigiosin production, and completely block protease activity. Moreover, xylitol decreased swimming motility, swarming motility and increased the sensitivity to hydrogen peroxide. The expression of rsmA, pigP, flhC, flhD fimA, fimC, shlA bsmB, and rssB genes that regulate virulence factor production was significantly downregulated by xylitol. In silico study showed that xylitol could bind with the SmaR receptor by hydrophobic interaction and hydrogen bonding, and interfere with the binding of the natural ligand with SmaR receptor. An in vivo mice survival test confirmed the ability of xylitol to protect mice against the virulence of S. marcescens. In conclusion, xylitol is a growth and virulence inhibitor in S. marcescens and can be employed for the treatment of S. marcescens wound and burn infections.

Emergence of antimicrobial resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Infections caused by resistant bacteria lead to up to two-fold higher rates of adverse outcomes compared with similar infections caused by susceptible strains. The negative impacts of antibacterial resistance can be measured at the patient level by increased morbidity and mortality, at the healthcare level by increased resource utilization, higher costs and reduced hospital activity and at the society level by antibiotic treatment guidelines favoring increasingly broad-spectrum empiric therapy.In this study 67 isolates were collected from patients admitted to ICUs of Zagazig University Hospitals, Sharqia, Egypt. The isolates were biochemically identified and their susceptibility to different antimicrobials were tested by Kirby-Bauer standard disk diffusion method.The results showed that the recovered bacteria had high degree of resistance to different antimicrobial classes and 86.25 % were multi drug resistance (MDR). In conclusion high rate of MDR were found in this study that necessitate strict antibiotic dispensing policy to reduce the increased antibiotic resistance.

Carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by extended-spectrum beta lactamases producing Enterobacteriaceae. The emergence of carbapenem-resistant organisms is worrisome due to the limited treatment options. Detection of carbapenemase-producing bacteria is critical for the choice of appropriate therapy. However, Inhibition of carbapenemases is an alternative approach to combat resistance to carbapenms. In this study, Escherichia coli and Klebsiella pneumoniae carbapenem resistant isolates were recovered from 300 clinical isolates. They were subjected phenotypically for detection of class B metallo-carbapenemase (MBL) producers (by carbapenem disks with or without EDTA), and were subjected for confirmation genotypically by PCR. In addition, the synergistic activities of MBL-inhibitors in combination with carbapenems were elucidated. Two E. coli and 15 K. pneumoniae isolates were carbapenem resistant. The genes encoding blaNDM-1 carbapenemase were detected in 16/17 isolates solely, or collaboratively with either blaVIM, or blaIMP or both in all carbapenem resistant isolates, by PCR method. The VIM-carbapenemase was encoded by one isolate. In pre-clinical trials for development of MBL-specific inhibitors, Sub-inhibitory concentrations of citric acid, malic acid, ascorbic acid and ciprofloxacin in combination with imipenem or meropenem exerted synergistic activities against metallo-carbapenemases. Their activities are probably attributed to the chelation of zinc ions in the active site of carbapenemase. Conclusively, these promising combined therapies might represent a new strategy for combating such serious infections caused by metallo-B-carbapenemase producers of K. pneumoniae and E. coli isolates.

In this work, we report on the influence of fabrication conditions and on the performance and stability of co-evaporated vapor deposited methyl ammonium lead iodide (MAPbI3) perovskite solar cells. It is shown that as the substrate temperature increases, one has to increase the flux of MAI as indicated by higher vapour pressure in the reactor to maintain the appropriate stoichiometry of the devices. The pressure of MAI was maintained at 5.5–6 × 10−5 Torr and PbI2 rate of deposition was maintained at 0.75 A/s for a room temperature substrate deposition. For higher substrate temperature depositions at 50 °C and 75 °C we had to elevate the MAI pressure because of re-evaporation of MAI from the substrate at higher temperatures. A power conversion efficiency of > 17.4% has been achieved with a p-i-n device architecture of FTO/PTAA (polytriaryl amine)/MAPbI3/PCBM (phenyl-C61-butyric acid methyl ester)/Al through careful control of the MAI pressure and PbI2 evaporation rate. Higher substrate temperature devices showed improved grain sizes. The devices do not show any hysteresis. Devices deposited at higher substrate temperatures are significantly more photo stable over 100 h of continuous light exposure in nitrogen ambient.

Background: Quorum sensing inhibitionis an advanced strategy that aims to interfere with bacterial cell-to-cell communication systems (quorum sensing), which regulate virulence factors production in Pseudomonas aeruginosa, in order to overcome the globalcrisis of antimicrobial resistance. Objectives: Study the potential quorum sensing inhibitory effect of Zinc oxide (ZnO)nanoparticlesin Pseudomonas aeruginosa and the impact on production of virulence factors. Methods: Quorum sensing inhibitory effect of ZnO was evaluated by assessing its ability to reducePseudomonas aeruginosa virulence factors production; rhamnolipids, pyocyanin, pyoverdin, hemolysins, elastase and proteases. Furthermore, qRT-PCR was performed to determine ZnO inhibitory effect onQS-regulatory geneslasI, lasR,rhlI, rhlR, pqsA and pqsR that control virulence factors secretion. Moreover, mice survival test was conducted to investigate the influence of ZnO on Pseudomonas aeruginosa-induced mortality in vivo. Results: ZnO revealed a statistically significant reduction in the production of QS-controlled virulence factors rhamnolipids, pyocyanin, pyoverdin, hemolysins, elastase and proteases. Furthermore, ZnO exhibited a significant decrease in the relative expression of QS-regulatory geneslasI, lasR,rhlI, rhlR,pqsA and pqsR. Additionally, ZnO significantly reduced the pathogenesis of Pseudomonas aeruginosa in vivo Conclusion: ZnO nanoparticles can be used as a quorum sensing inhibitor in Pseudomonas aeruginosa infections either as an adjuvant or alternative to conventional antimicrobials. Keywords: Pseudomonas aeruginosa, ZnO, quorum sensing, virulence inhibition.

Background Pancreatic cancer is one of the most serious and lethal human cancers with a snowballing incidence around the world. The natural product celastrol has also been widely documented as a potent anti-inflammatory, anti-angiogenic, and anti-oxidant. Purpose To elucidate the antitumor effect of celastrol on pancreatic cancer cells and its modulatory role on whole genome expression. Methods The antitumor activity of celastrol on a panel of pancreatic cancer cells has been evaluated by Sulforhodamine B assay. Caspase 3/7 and histone-associated DNA fragments assays were done for apoptosis measurement. Additionally, prostaglandin (PGE2) inhibition was evaluated. Moreover, a microarray gene expression profiling was carried out to detect possible key players that modulate the antitumor effects of celastrol on cells of pancreatic cancer. Results Our findings indicated that celastrol suppresses the cellular growth of pancreatic cancer cells, induces apoptosis, and inhibits PGE2 production. Celastrol modulated many signaling genes and its cytotoxic effect was mainly mediated via over-expression of ATF3 and DDIT3, and down-expression of RRM2 and MCM4. Conclusion The current study aims to be a starting point to generate a hypothesis on the most significant regulatory genes and for a full dissection of the celastrol possible effects on each single gene to prevent the pancreatic cancer growth., Graphical Abstract

(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC50 of 0.32, 0.16, and 1.29 &micro, M, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.