In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

Effects of Osseodensification on Immediate Implant Placement: Retrospective Analysis of 211 Implants

Osseodensification is a new method of bone instrumentation for dental implant placement that preserves bulk bone and increases primary implant stability, and may accelerate the implant rehabilitation treatment period and provide higher success and survival rates than conventional methods. The aim of this retrospective study was to evaluate and discuss results obtained on immediate implant placement with immediate and delayed loading protocols under Osseodensification bone instrumentation. This study included private practice patients that required dental implant rehabilitation, between February 2017 and October 2019. All implants were placed under Osseodensification and had to be in function for at least 12 months to be included on the study. A total of 211 implants were included in the study, with a 98.1% total survival rate (97.9% in the maxilla and 98.5% in the mandible). For immediate implants with immediate load, 99.2% survival rate was achieved, and 100% survival rate for immediate implant placement without immediate load cases. A total of four implants were lost during this period, and all of them were lost within two months after placement. Within the limitations of this study, it can be concluded that Osseodensification bone instrumentation provided similar or better results on survival rates than conventional bone instrumentation.     

Recycled Untreated Rubber Waste for Controlling the Alkali–Silica Reaction in Concrete

Recycled rubber waste (RW) is produced at an alarming rate due to the deposition of 1.5 billion scrap tires annually around the globe, which causes serious threats to the environment due to its open land filling issues. This study investigates the potential application of RW in concrete structures for mitigating the alkali–silica reaction (ASR). Various proportions of RW (5%, 10%, 15%, 20%, and 25%) partially replaced the used aggregates. RW was procured from a local rubber recycling unit. Cubes, prisms, and mortar bar specimens were prepared using a mixture design recommended by ASTM C1260 and tested for evaluating the compressive and flexural strengths and expansion in an ASR conducive environment for specimens incorporating RW. It was observed that the compressive and flexural strength decreased for specimens incorporating RW compared to that of the control specimens without RW. For example, an 18% and an 8% decrease in compressive and flexural strengths, respectively, were observed for specimens with 5% of RW by aggregates volume at 28 days. Mortar bar specimens without RW showed an expansion of 0.23% and 0.28% at 14 and 28 days, respectively, indicating the potential ASR reactivity in accordance with ASTM C1260. A decrease in expansion was observed for mixtures incorporating RW. Specimens incorporating 20% of RW by aggregate volume showed expansions of 0.17% at 28 days, within the limit specified by ASTM C1260. Moreover, specimens incorporating RW showed a lower reduction in compressive and flexural strengths under an ASR conducive environment compared to that of the control specimen without RW. Micro-structural analysis also showed significant micro-cracking for specimens without RW due to ASR. However, no surface cracks were observed for specimens incorporating RW. It can be argued that the use of RW in the construction industry assists in reducing the landfill depositing issues with the additional benefit of limiting the ASR expansion.     

Evaluation of Moisture Damage Potential in Hot Mix Asphalt Using Polymeric Aggregate Treatment

To enhance the moisture damage performance of hot mix asphalt (HMA), treating the aggregate surface with a suitable additive was a more convenient approach. In this research, two types of aggregate modifiers were used to study the effect of moisture damage on HMA. Three different aggregate sources were selected based on their abundance of use in HMA. To study the impact of these aggregate modifiers on moisture susceptibility of HMA, the indirect tensile strength test and indirect tensile modulus test were used as the performance tests. Moisture conditioning of specimens was carried out to simulate the effect of moisture on HMA. The prepared samples’ tensile strength ratio (TSR) and stiffness modulus (Sm) results indicated a decrease in the strength of the HMA after moisture conditioning. After treating the aggregate surface with additives, an improvement was seen in dry and wet strength and stiffness. Moreover, an increasing trend was observed for both additives. The correlation between TSR and strength loss reveals a strong correlation (R² = 0.7219). Also, the two additives indicate increased wettability of asphalt binder over aggregate, thus improving the adhesion between aggregate and asphalt binder.     

Vanillin-crosslinked chitosan/ZnO nanocomposites as a drug delivery system for 5-fluorouracil: study on the release behavior via mesoporous ZrO2–Co3O4 nanoparticles modified sensor and antitumor activity

Herein, a series of vanillin-crosslinked chitosan (Vn-CS) nanocomposites (NCs) containing various contents of ZnO nanoparticles (NPs) was prepared and characterized via FTIR spectroscopy, XRD, TGA, SEM and TEM. Changing the weight% of ZnO NPs in the prepared NCs resulted in an improvement in their antibacterial activity against Gram-negative and Gram-positive bacteria strains compared with the unmodified CS, and the encapsulation efficiency of 5-fluorouracil (5-FU) was found to be in the range of 61.4–69.2%. Subsequently, the release of 5-FU was monitored utilizing the mesoporous ZrO₂–Co₃O₄ NPs modified carbon paste sensor via the square-wave adsorptive anodic stripping voltammetry (SW-AdASV) technique. Also, the release mechanism of 5-FU from each NC was studied by applying the zero-order, first-order, Hixson–Crowell and Higuchi models to the experimental results. The cytotoxicity of prepared NCs and 5-FU-encapsulated NCs was evaluated against the HePG-2, MCF-7 and HCT-116 cancer cell lines, in addition to the WI-38 and WISH normal cell lines using the MTT assay. Notably, 5-FU/CV₁₀ NC exhibited the highest antitumor activity towards all tested cancer cell lines and a moderate activity against WI-38 and WISH normal cell lines with IC₅₀ values of 28.02 ± 2.5 and 31.65 ± 2.7 μg mL⁻¹, respectively. The obtained nanocomposites exhibited suitable selectivity with minimum toxicity against normal cells.

Herein, a series of vanillin-crosslinked chitosan (Vn-CS) nanocomposites (NCs) containing various contents of ZnO nanoparticles (NPs) was prepared and characterized via FTIR spectroscopy, XRD, TGA, SEM and TEM.     

Quaking and miR-155 interactions in inflammation and leukemogenesis

Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas expression and the rate of Caspase3/7 activity, while increasing the levels of IL-1α, IL-1β and IL-6, and p38 phosphorylation. Similarly, the p38 pathway is also a target of QKI activity in chronic lymphocytic leukemia (CLL)-derived MEC2 cells. Finally, B-CLL patients show lower levels of QKI expression compared with B cells from healthy donor, and Qki is similarily downregulated with the progression of leukemia in Eμ-miR-155 transgenic mice. Altogether, these data implicate QKI in the pathophysiology of inflammation and oncogenesis where miR-155 is involved.     

MERS coronavirus outbreak: Implications for emerging viral infections

In September 2012, a novel coronavirus was isolated from a patient who died in Saudi Arabia after presenting with acute respiratory distress and acute kidney injury. Analysis revealed the disease to be due to a novel virus which was named Middle East Respiratory Coronavirus (MERS-CoV). There have been several MERS-CoV hospital outbreaks in KSA, continuing to the present day, and the disease has a mortality rate in excess of 35%. Since 2012, the World Health Organization has been informed of 2220 laboratory-confirmed cases resulting in at least 790 deaths. Cases have since arisen in 27 countries, including an outbreak in the Republic of Korea in 2015 in which 36 people died, but more than 80% of cases have occurred in Saudi Arabia.. Human-to-human transmission of MERS-CoV, particularly in healthcare settings, initially caused a ‘media panic’, however human-to-human transmission appears to require close contact and thus far the virus has not achieved epidemic potential. Zoonotic transmission is of significant importance and evidence is growing implicating the dromedary camel as the major animal host in spread of disease to humans. MERS-CoV is now included on the WHO list of priority blueprint diseases for which there which is an urgent need for accelerated research and development as they have the potential to cause a public health emergency while there is an absence of efficacious drugs and/or vaccines. In this review we highlight epidemiological, clinical, and infection control aspects of MERS-CoV as informed by the Saudi experience. Attention is given to recommended treatments and progress towards vaccine development.     

A prospective randomised comparative study of endoscopic band ligation versus injection sclerotherapy of bleeding internal haemorrhoids in patients with liver cirrhosis

Background and study aimsBleeding internal haemorrhoids are common and used to be treated surgically with too many complications. Endoscopic therapy is trying to take the lead. Sclerotherapy and rubber band ligation are the candidates to replace surgical therapy especially in patients with liver cirrhosis. The aim of this study was to compare endoscopic injection sclerotherapy (EIS) to endoscopic rubber band ligation (EBL) regarding effectiveness and complications in the treatment of bleeding internal haemorrhoids in Egyptian patients with liver cirrhosis.Patients and methodsOne hundred and twenty adult patients with liver cirrhosis and bleeding internal haemorrhoids were randomised into two equal groups; the first treated with EBL using Saeed multiband ligator, and the second with EIS using either ethanolamine oleate 5% or N-butyl cyanoacrylate. All groups were matched as regards age, sex, Child score and pre-procedure Doppler values. Patients were followed up clinically and with abdominal ultrasound/Doppler for 6 months. Endoscopic and endosonography/Doppler was done before and one month after the procedure. Pre and post-procedure data were recorded and analysed.ResultsBoth techniques were highly effective in the control of bleeding from internal haemorrhoids with a low rebleeding [10% in the EBL group and 13.33% in the EIS group] and recurrence [20% in the EBL group 20% in the EIS group] rates. Child score had a positive correlation with rebleeding and recurrence in EIS group only.Pain score and need for analgesia were significantly higher while patient satisfaction was significantly lower in EIS compared to EBL [p < 0.05]. No significant difference between ethanolamine and cyanoacrylate subgroups was found [p > 0.05].ConclusionsBoth EBL and EIS were effective in the treatment of bleeding internal haemorrhoids in patients with liver cirrhosis. EBL had significantly less pain and higher patient satisfaction than EIS. EBL was also safer in patients with advanced cirrhosis.