Exploring the anticancer activities of novel bioactive compounds derived from endophytic fungi: mechanisms of action,current challenges and future perspectives

Cancer is the second leading cause of death all around the world. The natural compounds derived from the endophytic flora of fungi are possible solutions to cancer treatment because they are safe for health, cost-effective, biocompatible and have fewer toxicity issues. The active ingredients in endophytic fungi that are responsible for anti-cancer activities are alkaloids, terpenoids, glycosides, saponin, peptides, steroids, phenols, quinones, and flavonoids. This review highlights the anti-cancer activities of entophytic fungus against human papillary thyroid carcinoma (IHH4), human pancreatic (PANC-1), ovarian (OVCAR-3), hepatic (HepG2), lung (A-549), human lymphoma (U937), human skin carcinoma (A431), breast (MCF-7), and Kaposi’s sarcoma. The emerging evidence suggested that bioactive compounds isolated from endophytic fungi showed their anti-cancer activities by revealing the disturbance of the microtubule network caused by increased levels of Bax and Bcl-2 proteins that triggers cell cycle arrest at the G2-M phase, by inhibiting the DNA replication via binding with topoisomerase II, by regulating the activity of extracellular signal-regulated kinase and NF-kB, by evaluating the levels of p21, p27, and cyclins B/D1/E that led to cell death by apoptosis and cell cycle arrest. This review will assist readers in better comprehending bioactive chemicals and the beneficial interaction between the fungal endophytes and medicinal plants.     

Association of dry eye disease with smoking: A systematic review and meta-analysis

There is conflicting evidence for the association between smoking and dry eye disease (DED). We conducted a meta-analysis to determine the true relationship between smoking and DED. A systematic literature search was performed using electronic databases, including PubMed, Embase and Cochrane Library, till August 2021 to identify observational studies with data on smoking as risk factor of DED. Quality assessment of the included studies was conducted using Joanna Briggs Institute (JBI) critical appraisal checklists. The random-effects model was used to calculate the pooled odds ratio (OR). Heterogeneity was evaluated by Cochrane Q and I² index; in addition, subgroup, sensitivity, and meta-regression analyses were performed. Publication bias was assessed using funnel plot and Egger’s regression test. A total of 22 studies (4 cohort and 18 cross-sectional studies) with 160,217 subjects met the inclusion criteria and were included in this meta-analysis. There is no statistically significant relationship between current smokers (OR_adjusted = 1.14; 95% CI: 0.95–1.36; P = 0.15; I² = 84%) and former smokers (OR_adjusted = 1.06; 95% CI: 0.93–1.20; P = 0.38; I² = 26.7%) for the risk of DED. The results remained consistent across various subgroups. No risk of publication bias was detected by funnel plot and Eggers’s test (P > 0.05). No source of heterogeneity was observed in the meta-regression analysis. Our meta-analysis suggest current or former smoking may not be involved in the risk of dry eye disease. Further studies to understand the mechanism of interaction between current smokers and formers smokers with DED are recommended.     

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.     

Resistance of Xanthomonas oryzae pv. oryzae to Lytic Phage X2 by Spontaneous Mutation of Lipopolysaccharide Synthesis-Related Glycosyltransferase

Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives.     

Cytotoxic effects of extracts obtained from plants of the Oleaceae family: bio-guided isolation and molecular docking of new secoiridoids from Jasminum humile

ContextTraditionally, Oleaceae plants are used to treat many diseases, such as rheumatism, hypercholesterolaemia, or ulcers.ObjectivesTo investigate the cytotoxic potential of Jasminum humile L., Jasminum grandiflorum L., and Olea europaea L. (Oleaceae) extracts against selected human cancer cells lines, followed by a phytochemical investigation of the most potent one.Materials and methodsThe 95% ethanol extracts of aerial parts of three oleaceous plants were examined for their cytotoxicity against HepG-2, MCF-7, and THP-1 cell lines using MTT assay and doxorubicin (positive control). J. humile was bio-selected and submitted to bio-guided fractionation. Chromatographic workup of ethyl acetate and n-butanol fractions afforded two new compounds; 1-methoxyjasmigenin (1) and 1-methyl-9-aldojasmigenin (2), along with five known ones (3–7). Structures were unambiguously elucidated using 1D/2D NMR and ESI-HRMS. Isolated compounds were assessed for their anti-proliferative potential, and both selectivity index and statistical significance were determined. Molecular docking was conducted against the Mcl-1 receptor using (AZD5991) as a standard.ResultsJasmoside (5) was the most potent anticancer compound showing IC₅₀ values of 66.47, 41.32, and 27.59 µg/mL against HepG-2, MCF-7, and THP-1 cell lines, respectively. Moreover, isojasminin (4) exhibited IC₅₀ values of 33.49, 43.12, and 51.07 µg/mL against the same cell lines, respectively. Interestingly, 5 exhibited the highest selectivity index towards MCF-7 and THP-1, even greater than doxorubicin. Molecular docking results were in full agreement with the MTT assay and the proposed SAR.ConclusionIn this study, two new compounds were purified. The biological activity highlighted jasmoside (5) as a lead anticancer drug for further future investigation.     

Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease

JUSTIFICATION: Acute rheumatic fever and rheumatic chronic valvular heart disease is an important preventable cause of morbidity and mortality in suburban and rural India. Its diagnosis is based on clinical criteria. These criteria need verification and revision in the Indian context. Furthermore, there are glaring differences in management protocols available in literature. These facts prompted Indian Academy of Pediatrics to review the management of rheumatic fever. PROCESS: Management of Rheumatic fever was reviewed and recommendation was formulated at national consultative meeting on 20th May 2007 at New Delhi. OBJECTIVES: To formulate uniform guidelines on management of acute rheumatic fever and rheumatic heart disease in the Indian context. Guidelines were formulated for the management of streptococcal pharyngitis, acute rheumatic fever and its cardiac complication as well as secondary prophylaxis for recurrent episodes. RECOMMENDATIONS: (1) Streptococcal eradication with appropriate antibiotics (Benzathine penicillin single dose or penicillin V oral or azithromycin). (2) Diagnosis of rheumatic fever based on Jones criteria. (3) Control inflammatory process with aspirin with or without steroids (total duration of treatment of 12 weeks). (4) Treatment of chorea according to severity (therapy to continue for 2-3 weeks after clinical improvement). (5) Protocol for managing cardiac complication like valvular heart disease, congestive heart failure and atrial fibrillation. (6) Secondary prophylaxis with benzathine penicillin and management of anaphylaxis.     

Introduction of cadmium chloride additive to improve the performance and stability of perovskite solar cells

With the increase in the importance of using green energy sources to meet the world''s energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world. Improving the properties of perovskite materials as the heart of PSCs is one of the methods to fabricate favorable photovoltaic (PV) solar cells based on perovskites. Here, cadmium chloride (CdCl₂) was used as an additive source for the perovskite precursor to improve its PV properties. Results indicated CdCl₂ improves the perovskite growth and tailors its crystalline properties, suggesting boosted charge transport processes in the bulk and interfaces of the perovskite layer with electron–hole transport layers. Overall, by incorporation of 1.0% into the MAPbI₃ layer, a maximum power conversion efficiency of 15.28% was recorded for perovskite-based solar cells, higher than the 12.17% for the control devices. The developed method not only improved the PV performance of devices but also boosted the stability behavior of solar cells due to the passivated domain boundaries and enhanced hydrophobicity in the CdCl₂-based devices.

With the increase in the importance of using green energy sources to meet the world''s energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world.     

Effect of Zr and Ti Addition and Aging Treatment on the Microstructure and Tensile Properties of Al-2%Cu-Based Alloys

The present work investigated the effect of aging treatment on the microstructure and tensile properties of an Al-2%Cu base alloy containing various additions of Zr and other alloying elements. Aging was carried out at temperatures of 180–300 °C for different aging times at each temperature. The tensile properties indicated that Zr additions improved the strength of the base alloy, especially at high Zr levels at 180 °C. At the 220 °C aging temperature, however, while Zr addition did not have a beneficial effect on the alloy strength, the ductility was found to improve. Zr-Ti combined additions had a significant effect on the microstructure of the base alloy, as the morphology of the α-Al grains transformed into a non-dendritic morphology, and the grain size decreased sharply. These effects were at their maximum at 180 °C and 0.5 wt% Zr addition. Moreover, the Zr-containing alloys aged at higher temperatures, such as 220 °C and 240 °C, maintained a noticeably higher level of strength over the base alloy aged at the same temperatures. Quality index charts based on the tensile test data also reflected an improvement in alloy quality and strength with Zr-Ti combined additions.     

Influence of Cross-Section Shape and FRP Reinforcement Layout on Shear Capacity of Strengthened RC Beams

The evaluation of the shear capacity of an FRP-strengthened reinforced-concrete beam is challenging due to the complex interaction between different contributions provided by the concrete, steel stirrup and FRP reinforcement. The shape of the beam and the FRP inclination can have paramount importance that is not often recognized by the models that are suggested by codes. The interaction among different resisting mechanisms has a significant effect on the shear capacity of beams, since it can cause a reduction in the efficiency of some resisting mechanisms. A comparative study of the performance in the shear resistance assessment provided by three models with six different effectiveness factors (R) is performed, considering different cross-section shapes, FRP wrapping schemes, inclination and anchorage systems. The results revealed that the cross-section shape, the FRP inclination and the efficiency of the FRP anchorages have a significant effect on the shear strength of beams. The analysis results show that the three models are able to provide an accurate average estimation of shear strength (but with a coefficient of variation up to 0.35) when FRP reinforcement orthogonal to the beam axis is considered, while a significant underestimation (up to 19%) affected the results for inclined FRP reinforcement. Moreover, all the models underestimated the resistance of beams with a T section.