Search

Abstract This study aimed to evaluate alternative in vivo treatment trials using natural products for ectoparasitic infestation on Nile tilapia; these two products were not previously used in the treatment of parasitic fish diseases. So, a total of 400 Oreochromis niloticus (O. niloticus) fish measured 10–15 cm in length; 350 from a fish farm in (Kafr Elsheikh and 50 from Nile River (Al Bahr Al Aazam), Egypt. The examined fishes were 10–15 ± 0.5 cm long and weighed from 45 g ± 5. The collected fish were examined for different clinical abnormalities. Each part of the fish underwent a careful microscopic examination of mucous surrounding the skin; gills and fins. Two feed supplements were used experimentally to decrease mortality and treat fish against ectoparasites (Herb-All PARA-X® and Herb-All CALM®). Total mRNA was extracted from the gills of different examined groups. Glucose; nitric oxide; cortisol as well as lysozyme activity were assessed in all groups. The gills of the examined fish were collected for histopathological examination. Only, Dactyolgyrus sp. was recovered. The intensity of the parasite was counted per microscopic field. The treated groups showed low levels of the parameters compared to the control positive group. Up-regulation of both Tumor necrosis factor-α (TNF- α) and heat shock protein 70 (hsp-70) were detected in fins, gills, and skin in the infested tilapia. The treatment and prophylaxis significantly downregulated both genes in the studied organ in a dose-dependent manner. Recorded lesions which were scored according to their severity. In conclusion; following the use of those products, fish health has been greatly improved and that is indicated by findings of immune reactions as well as histopathology.

Abstract The global focus has recently shifted away from fuel-based power sources, and one of the most important projects for energy production is wind energy. To maintain low costs, the current research examines the problem of vibrations affecting wind turbine towers’ performance (WTTs). In particular, the tower, resulting from excessive vibrations, can negatively affect a structure’s power output and service life, as it can cause fatigue. Therefore, we conducted numerical tests on various types of controlled systems. Our tests revealed that combining a new technique cubic negative velocity control (CNVC) and linear negative acceleration control (LNAC) was the most effective and cost-efficient option for vibration damping. This solution was derived by using an approximation method for the averaging technique. The external force is an important component of a nonlinear dynamic system and can be characterized by two-degree-of-freedom (2-DOF) differential coupled equations. After implementing the control measures, we conducted a numerical analysis of the vibration values before and after the operation. Stability is studied numerically. The numerical and approximate solutions were confirmed through the frequency response equation and time history with fourth-order Runge–Kutta (RK-4). Finally, we investigated the effect of parameters and compared our results with those of previously published studies.

Abstract To arrive at an equivalent linear differential equation, the non-perturbative approach (NPA) is established. The corresponding linear equation is employed for performing the structural analysis. A numerical computation demonstrates a high consistency with the precise frequency. The correlation with the numerical solution explains the reasonableness of the obtained solutions. For additional nonlinear kinds of oscillation, the methodology gives an exact simulation. The stable construction of the prototype is shown in a series of diagrams. Positive position feedback (PPF), integral resonant control (IRC), nonlinear integral positive position feedback (NIPPF), and negative derivative feedback (NDF) are proposed to get rid of the damaging vibration in the system. It is found that the NDF control is more efficient than other controllers for vibration suppression. The theoretical methodology is applied by using the averaging method for getting a perturbed solution. The stability and influence of various parameters of the structure are established at main and 1:1 internal resonance, which is presented as one of the worst resonance cases. Association concerning mathematical solution and computational simulation is achieved.

Abstract A series of new coumarin-N-heterocyclic hybrids, coumarin-quinolines 7a–e, coumarin-acridines 10b,c and coumarin-neocryptolepines 13b,c were synthesized and evaluated for their anticancer and antimicrobial activities. The structures of all synthesized hybrids were confirmed by FT-IR, 1H-NMR, 13C-NMR, and MS spectrometry. The anti-proliferative activity of hybrids 7a–e, 10c and 13c were bio-evaluated using MTT-assay against colon (CaCo-2), lung (A549), breast (MDA-MB-231), and hepatocellular carcinoma (HepG-2) human cancer cell lines using doxorubicin as a reference drug. The results demonstrated that, all hybrids displayed moderate to good anti-proliferative activity against the cell lines. The most active hybrids were 7a–d and 10c against CaCo-2 cancer cell line with IC50: 57.1, 52.78, 57.29, 51.95 and 56.74 µM, and selectivity index 1.38, 1.76, 2.6, 1.96 and 0.77; respectively. While, 7a,d were potent against A549 cancer cell line with IC50: 51.72, 54.8 µM and selectivity index 1.5, 0.67; respectively. Moreover, 7c showed the most potency against MDA-MB-231 cancer cell line with IC50: 50.96 µM and selectivity index 2.20. Interestingly, docking results revealed that binding energy of the current compounds showed marked affinity values ranging from -6.54 to -5.56 kcal with interactions with the reported key amino acid SER 79. Furthermore, the antimicrobial activity of the synthesized hybrids 7a–e, 10b,c, 13b and 13c were evaluated against Gram‐positive and Gram‐negative bacterial and fungal strains. The hybrids 10b, 13b, 10c, and 13c exhibited broad-spectrum antibacterial activity against E.coli, S. mutans, and S. aureus with MIC from 3.2 to 66 µM, this hybrids also displayed antifungal activity against C. albicans with MIC values ranging from 0.0011 to 29.5 µM. In-silico investigation of the pharmacokinetic properties indicated that tested hybrids had high GI absorption, low Blood Brain Barrier (BBB) permeability in addition to cell membrane penetrability.

This article contemplates the demeanor of the giant magnetostrictive actuator (GMA) when a positive position feedback (PPF) damper is used to enable tight control over its vibration. The methodology followed here mathematically searches for the approximate solution for the motion equations of the GMA with the PPF damper, which has been accomplished by using one of the most famous perturbation methods. The multiple scale perturbation technique (MSPT) of the second-order approximation is our strategy to obtain the analytical results. The stability of the system has also been investigated and observed by implementing frequency response equations to close the concurrent primary and internal resonance cases. By utilizing Matlab and Maple programs, all numerical discussions have been accomplished and explained. The resulting influence on the amplitude due to changes in the parameters' values has been studied by the frequency response curves. Finally, a comparison between both the analytical and numerical solutions using time history and response curves is made. In addition to the comparison between our PPF damper's effect on the GMA, previous works are presented. To get our target in this article, we have mentioned some important applications utilized in the GMA system just to imagine the importance of controlling the GMA vibration.

Abstract The inverted pendulum is controlled in this article by using the nonlinear control theory. From classical analytical mechanics, its substructure equation of motion is derived. Because of the inclusion of the restoring forces, the Taylor expansion is employed to facilitate the analysis. An estimated satisfactory periodic solution is obtained with the aid of the modified Homotopy perturbation method. A numerical technique based on the fourth-order Runge–Kutta method is employed to justify the previous solution. On the other hand, a positive position feedback control is developed to dampen the vibrations of an IP system subjected to multi-excitation forces. The multiple time scale perturbation technique of the second order is introduced as a mathematical method to solve a two-degree-of-freedom system that simulates the IP with the PPF at primary and 1:1 internal resonance. The stability of these solutions is checked with the aid of the Routh–Hurwitz criterion. A set of graphs, based on the frequency response equations resulting from the MSPT method, is incorporated. Additionally, a numerical simulation is set up with RK-4 to confirm the overall controlled performance of the studied model. The quality of the solution is confirmed by the match between the approximate solution and the numerical simulation. Numerous other nonlinear systems can be controlled using the provided control method. Illustrations are offered that pertain to implications in design and pedagogy. The linearized stability of IP near the fixed points as well as the phase portraits is depicted for the autonomous and non-autonomous cases. Because of the static stability of the IP, it is found that its instability can be suppressed by the increase of both the generalized force as well as the torsional constant stiffness of the spring. Additionally, the presence of the magnetic field enhances the stability of IP.

Abstract In the sight of the ever-increasing significance of green-based iron nanoparticles especially in wastewater treatment applications is a compelling reason for their use in a waste prevention opportunity, safer environment and benign precursor materials become the vital considerations. Hence, in the current investigation, an efficient co-precipitation technique was applied to prepare highly active chitosan-coated magnetic iron oxide that is applied for wastewater remediation. In the current investigation, chitosan coupled with magnetite nanoparticles namely CS-M was attained by coupling chitosan (CS) with magnetite nanoparticles via simple co-precipitation in different weight proportions and the attained samples labeled as CS-M-(2:1), CS-M-(3:1) and CS-M-(1:2). The structure, morphology and characteristics of the prepared samples were characterized using X-ray diffraction spectroscopy and transmission electron microscopy (TEM). The catalytic oxidation activity of the prepared samples was investigated to eliminate Basic Blue 9 (BB9) dye from aqueous effluent as simulated textile polluted stream. The experimental data exposed almost BB9 dye emanation. The system parameters revealed the maximal BB9 oxidation (99%) was attained within 2 h of irradiance time. Box–Behnken design factorial design based on response surface methodology was applied to optimize the Fenton’s system (CS-M-(2:1)/H2O2) parameters to maximize the efficiency 2.4 and 767 mg/L of CS-M and H2O2, respectively, at pH 7.0. The experimental data exposed that CS-M-(2:1) is signified as the optimal catalyst mixture. The kinetic data verify the oxidation system follows the second-order reaction kinetic model. Further, thermodynamic variables predicted that the reaction is endothermic and non-spontaneous in nature. Hence, the catalyst could be environmental benign and the evaluation introduces the role of engineers and chemists in a world for a sustainable material use.

Abstract Background Early detection of hepatocellular carcinoma (HCC) is crucial for improving the survival rate for patients. Talin-1 is first identified as a cytoskeleton protein that is required for cell adhesion and motility and plays a role in tumor migration and metastasis. In the present work, we aimed to study the possible role of Talin1 compared to alpha fetoprotein (AFP) in the diagnosis and prognosis of HCC. Methods To achieve this goal, serum levels of Talin-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 90 patients divided into four groups. Group I: 30 patients with early HCC. Group II: 30 patients with late HCC according to Modified Barcelona-Clinic Liver Cancer (BCLC). Group III: 15 patients with liver cirrhosis, and group IV: 15 healthy controls. Receiver operating characteristics (ROC) curve analysis was used to create a predictive model for Talin-1 relative to AFP in HCC diagnosis. Results It was found that serum Talin-1 in HCC patients was significantly higher compared to its level in cirrhotic patients and the healthy control group. Talin-1 was superior to AFP regarding sensitivity, specificity, positive, and negative predictive value in the diagnosis of HCC. We also found a significant positive correlation between serum Talin-1 and the degree of tumor burden of HCC (BCLC staging), tumor size, and vascular invasion. Conclusion Talin-1 holds a promise as a potential marker for HCC diagnosis and prognosis.

Abstract This paper proposes a novel stochastic solution method for the static nonconvex power economic dispatch problem. All practical features such as valve point effects, ramp rate limits, prohibited operating zones, multiple fuel options, spinning reserve constraints, and transmission losses are considered. To develop the proposed algorithm, two modifications that significantly enhance the exploitation capability of the artificial bee colony algorithm are introduced. The first modification concerns onlooker and employed bees to focus their search around the best solution found so far. The second modification optimizes the escaping behavior from local minimums using scout bees. The proposed modifications form a multi‐level concentric search around the best solution found. Finally, combining the modified artificial bee colony algorithm with Levy flight cycles, which improve the escaping capability from local minimums, leads to the proposed algorithm. The algorithm parameters have been tuned to provide a deterministic‐like solution with ten benchmark problems. The improvement added by each proposed modification to the artificial bee colony algorithm has been confirmed using the Wilcoxon rank‐sum test. The obtained results by the proposed algorithm are superior compared to those reported in the literature. Moreover, estimated probabilities of more than 99.9% to obtain the global optimal solution are achieved.

Objectives: During the COVID-19 pandemic, a quick and reliable phone-triage system is critical for early care and efficient distribution of hospital resources. The study aimed to assess the accuracy of the traditional phone-triage system and phone triage-driven deep learning model in the prediction of positive COVID-19 patients. Setting: This is a retrospective study conducted at the family medicine department, Cairo University. Methods: The study included a dataset of 943 suspected COVID-19 patients from the phone triage during the first wave of the pandemic. The accuracy of the phone triaging system was assessed. PCR-dependent and phone triage-driven deep learning model for automated classifications of natural human responses was conducted. Results: Based on the RT-PCR results, we found that myalgia, fever, and contact with a case with respiratory symptoms had the highest sensitivity among the symptoms/ risk factors that were asked during the phone calls (86.3%, 77.5%, and 75.1%, respectively). While immunodeficiency, smoking, and loss of smell or taste had the highest specificity (96.9%, 83.6%, and 74.0%, respectively). The positive predictive value (PPV) of phone triage was 48.4%. The classification accuracy achieved by the deep learning model was 66%, while the PPV was 70.5%. Conclusion: Phone triage and deep learning models are feasible and convenient tools for screening COVID-19 patients. Using the deep learning models for symptoms screening will help to provide the proper medical care as early as possible for those at a higher risk of developing severe illness paving the way for a more efficient allocation of the scanty health resources.

Objectives Early detection of coronavirus disease 2019 (COVID-19) is crucial for patients and public health to ensure pandemic control. We aimed to correlate clinical and laboratory data of patients with COVID-19 and their polymerase chain reaction (PCR) results and to assess the accuracy of a deep learning model in diagnosing COVID-19. Methods This was a retrospective study using an anonymized dataset of patients with suspected COVID-19. Only patients with a complete dataset were included (n = 440). A deep analytics framework and dual-modal approach for PCR-based classification was used, integrating symptoms and laboratory-based modalities. Results Participants with loss of smell or taste were two times more likely to have positive PCR results (odds ratio [OR] 1.86). Participants with neutropenia, high serum ferritin, or monocytosis were three, four, and five times more likely to have positive PCR results (OR 2.69, 4.18, 5.42, respectively). The rate of accuracy achieved using the deep learning framework was 78%, with sensitivity of 83.9% and specificity of 71.4%. Conclusion Loss of smell or taste, neutropenia, monocytosis, and high serum ferritin should be routinely assessed with suspected COVID-19 infection. The use of deep learning for diagnosis is a promising tool that can be implemented in the primary care setting.

In this paper, we introduced response analysis and controlling the nonlinear vibration of van der pol duffing oscillator subject to parametric and external excitations by connecting the nonlinear integral positive position feedback (NIPPF). The controller combines the characteristics of the positive position feedback controller (PPF) and integral resonant control (IRC) and these controllers are viewed in a blocked scheme for the closed-loop system (system under control). The analytical solution and all resonance cases are obtained by applying the multiple time scales perturbation method (MSPM). The stability analysis is studied using the frequency response equations at the supposed worst resonance case. For numerical simulation, the system is examined before and after connecting the NIPPF controller using Matlab software program (package ode45). The influences of different parameters are examined numerically for the vibrating system and controller. The approximate analysis is confirmed with numerical simulation outcomes. Finally, making a comparison with previously related published work.

The objective of this study was to prepare bile acidsbinding and tyrosinase inhibitory peptides for industrial potential application. Proteins were extracted from Brassica olercea (cauliflower) midribs, Corchorus olitorius (corchorus) stems and Vicia faba (broad bean) leaves then were subjected to hydrolysis by immobilized lettuce protease. For maximum peptides production, the influence of incubation temperatures, and substrate concentrations on the hydrolysis processes were investigated. Peptides were fractionated by ultrafiltration into three fractions according to their molecular weight. Corchorus (fractions F2 and F1) and broad bean (fraction F1) peptides showed bile acids-binding higher than that bind by cholestyramine resin. They may have potential application as a cholesterol-reducing agent for hypercholestermic patients. Cauliflower (F2 and F1) and corchorus (fraction F1) peptides showed tyrosinase inhibitor potency higher than that by kojic acid. They may have potential application as a whitening agent.

Taxol, a diterpenoid was initially isolated from the bark of Taxus brevifolia, approved by FDA in 1994 as a powerful drug for metastatic ovarian carcinoma, breast and lung cancer. However, due to limitations in the production of this drug based on this plant source, the productive potentiality of fungi of this compound opened a new avenue for its commercial production. In this study, among the twenty fungal isolates screened for Taxol production, Aspergillus terreus had the highest potentiality to produce Taxol (131.2 µg/ml). The productivity of Taxol by A. terreus has been maximized by nutritional optimization using inhibitors and growth regulators. The yield of Taxol by A. terreus was maximally obtained (0.663µg/ml) by growing the fungal isolate on potato dextrose broth medium, amended with addition of biotin at 150 µg/ml for 20 days. The chemical structure Taxol extracted of A. terreus has been verified by proton and carbon NMR, IR and UV analyses. The activity of A. terreus Taxol has been assessed towards multiple cell lines, displaying a strong anticancer activity. In conclusion, the productivity of Taxol by A. terreus has been greatly improved upon using biotin as chemical modulator, that open a new avenue for commercializing the Taxol yield by fungi.

Introduction The COVID-19 pandemic is an unprecedented challenge to house officers training programs because of the safety measures. Objective This current study aimed to introduce the adaptation of family medicine training for house officers during COVID-19 pandemic and gauge their level of satisfaction with the training. Methods Unfortunately, more than one-fourth of the house officers attending the family medicine training turned out to be hospital-admitted or in obligatory home isolation. A time-sensitive plan was proposed to maintain a competent training guaranteeing safety and support of house officers and fulfilling the training objectives in a virtual setting. Three mentors were assigned to each 10 house officers to provide continuous support and monitoring. Tutor and house officer interaction and reflection were maintained through a virtual clinical training session via Zoom application and a daily online discussion of a clinical scenario. Peer interaction was provided through post-webinar and small-group online discussion sessions. Results The adapted training was applied on thirteen cohorts of house officers. The response rate was 70% (666 out of 950). Most of them were satisfied with the training (84.6%). Their satisfaction with each modality of the training was encouraging. Conclusions During COVID-19 pandemic, successful adaptation of family medicine training has succeeded in fulfilling the training objectives and providing psychological support and engagement for house officers without burdening the hospital-admitted and home-isolated house officers.

Introduction: Cardiovascular disease (CVD) is the most leading cause of mortality worldwide. Changes in diet can reduce subclinical cardiac injury and inflammation in parallel with reductions of other CVD risk factors. Aim: The study aimed to evaluate the beneficial effect of the DASH diet versus usual healthy dietary advice (HDA) on the estimated risk of atherosclerotic cardiovascular disease (ASCVD). Methods: It was a prospective interventional nonrandomized controlled study, conducted on 92 participants attending Family Medicine Outpatient Clinics, Cairo University. The participants were assigned to 2 dietary groups, the DASH and HDA groups, for 12 weeks. All subjects were subjected to anthropometric measurement, assessment of lipid profile, and the estimated cardiovascular risk pre-and post-intervention. Results: The estimated cardiovascular risk was reduced significantly in both the DASH and HDA groups, with no statistically significant difference between the 2 groups regarding the risk reduction. By comparing the percent change between pre and post-intervention in both DASH and HDA groups, the following are the results: BMI dropped by 6.5% versus 2.5%, systolic blood pressure decreased by 6.9% and 4.1%, fasting blood sugar dropped by 5.5% and 3.1%, total cholesterol dropped by 5.2% and 3.1%, LDL dropped by 8.2%, and 3.1%, and HDL increased by 8.2% and 2.4%, in DASH and HDA groups, respectively. Conclusion: Both the DASH diet and HDA are associated with improvement in CVD risk factors. Although better risk factors decline with the DASH diet, there was no statistically significant difference between the 2 groups.

Evaluating the mechanism of tolerance and biotransformation Zn(II) ions by Fusarium solani based on the different physiological was the objective of this work. The physical properties of synthesized ZnONPs was determined by UV-spectroscopy, transmission electron microscope, and X-ray powder diffraction. The structural and anatomical changes of F. solani in response to Zn(II) was examined by TEM and SEM. From the HPLC profile, oxalic acid by F. solani was strongly increased by about 10.5 folds in response to 200 mg/l Zn(II) comparing to control cultures. The highest biosorption potential were reported at pH 4.0 (alkali-treated biomass) and 5.0 (native biomass), at 600 mg/l Zn(II) concentration, incubation temperature 30 °C, and contact time 40 min (alkali-treated biomass) and 6 h (native biomass). From the FT-IR spectroscopy, the main functional groups implemented on this remediation were C–S stretching, C=O C=N, C–H bending, C–N stretching and N–H bending. From the EDX spectra, fungal cellular sulfur and phosphorus compounds were the mainly compartments involved on ZN(II) binding.

Silver ions discharged from various industries, are potentially toxic to living organisms at low concentrations, thus, there is an increasing need for development of an eco-friendly and cost-effective approach for its bioremediation. Filamentous fungi especially, Fusarium solani displayed a strong resistance to copper and cadmium ions as revealed from our previous study (El-Sayed 2014), however, the mechanisms of silver resistance by this fungus has not been resolved yet. Thus, this study was an extension to our previous work, to elucidate the mechanism of silver ions resistance and biotransformation by F. solani. The growth, bioaccumulation, thiol, total antioxidant, malondialdehyde (MDA), hydrogen peroxide (H2O2) contents and polyphenol oxidase (PPO) and catalase (CAT) activities of F. solani in response to silver ions were determined. Production and bioaccumulation of silver nanoparticles was characterized by UV-visible spectroscopy, TEM, and X-ray powder diffraction (XRD). The ultrastructural changes of F. solani induced by Ag(I) was examined by TEM and SEM. Production of oxalic acid by F. solani was increased by about 343.8% in response to 400 mg/l Ag(I), compared to control cultures (without silver ions) as revealed from HPLC analysis. The maximum biosorption levels by the native and alkali-treated biomass were carried out at pH 5.0, initial metal concentration 200 mg/l, biomass 0.5 g/l, temperature 35 °C, and contact time 1 h (native biomass) and 3 h (alkali-treated biomass). Fourier transform infrared spectroscopy (FTIR) results revealed that the main functional groups involved on this mycoremediation were C–S stretching, C=O C=N, C – H bending, C–N stretching and N–H bending. EDX spectra indicated the involvement of fungal cellular sulfur and phosphorus compounds in Ag(I) binding.

Background The association between androgenetic alopecia (AGA) and cardiovascular risk is still controversial. Objective To evaluate the association between AGA and the risk of cardiovascular diseases (CVDs) using lipoprotein a [Lp (a)] and high-sensitivity C-reactive protein (hs-CRP) as biomarkers of cardiovascular risk. Patients and methods A case–control study was done on 30 patients with AGA and 25 healthy controls with normal hair status. Both patients and their controls were examined generally and locally. Classification of AGA was done according to Hamilton–Norwood scale for male patients and Ludwig’s classification for women. Hair examination was confirmed using dermoscopy for the assessment of signs of AGA. All participants were investigated for serum lipids including cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and Lp (a), in addition to hs-CRP. Results After exclusion of the well-known risk factors for CVD, AGA patients showed higher positive family history of CVD in first-degree relatives than the controls. Serum lipids including serum Lp (a) and hs-CRP were significantly higher in AGA patients. Lp (a) was positively correlated with hs-CRP in AGA patients. Both Lp (a) and hs-CRP were positively correlated with the severity of AGA in both men and women. Both markers did not correlate significantly with lipid parameters including cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein. There was no significant difference between men and women with AGA as regards the studied parameters. Both hs-CRP and Lp (a) showed significant discrimination using area under the receiver operating characteristic curve where Lp (a) showed area under the curve=0.928 with 95% confidence interval, 0.863–0.993 and P=0.001 while hs-CRP showed area under the curve=0.963 with 95% confidence interval 0.921–1.0, and P value less than 0.001. Multivariate logistic regression analysis showed that hs-CRP was the only significant independent factor affecting cardiac risk in AGA cases. Conclusion AGA patients showed higher risk for CVD. Both Lp (a) and hs-CRP can be used as a predictor for cardiovascular risk in such patients; however, hs-CRP is still considered an independent risk factor for cardiovascular insults in AGA patients.

Most of the shaft theories have based their analysis on bending moment, twisting moment or combined between them. Nevertheless, the dynamic behavior of flexural-torsional coupled vibrations in the rotating shafts is affected by the internal resistance forces due to torsion. It is expected that the deflected shafts shall be exposed to this resistance, where these forces were not considered in the analysis before. The objective of the present work was to estimate the effect of internal torsional resistance in shafts which is caused by deflection, for the reason that it has the upper hand on misalignment problem. With the aim of fulfilling this objective, an experimental rig has been constructed to verify the existence of the torsional resistance in deflected shafts and its variation with the rotation angle.

Mycotoxigenic fungi have attracted special attention due to their threat to food security and toxicity to human health. Aqueous extract of Zingiber officinale Roscoe was used as reducing and capping agent for the synthesis of silver (AgNPs), copper (CuNPs), and zinc oxide (ZnONPs) nanoparticles. UV-Visible spectra of the AgNPs, CuNPs, and ZnONPs showed absorption peaks at λmax 416 nm, 472 nm, and 372 nm, respectively. Zeta potential of AgNPs, CuNPs, and ZnONPs were −30.9, −30.4 and −18.4 mV, respectively. ZnONPs showed the highest activity against Aspergillus awamori ZUJQ 965830.1 (ZOI 20.9 mm and MIC 24.7 µg/mL). TEM micrographs of ZnONPs-treated A. awamori showed cracks and pits in the cell wall, liquefaction of the cytoplasmic content, making it less electron-dense. The sporulation and ochratoxin A production of A. awamori was inhibited by ZnONPs in a concentration-dependent pattern. The inhibition percentage of OTA were 45.6, 84.78 and 95.65% for 10, 15, 20 of ZnONPs/mL, respectively.

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids “Taxol” is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree, Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark of T. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi from Taxus spp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.