Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

Outcome Evaluation on Impact of the Nutrition Intervention among Adolescents: A Feasibility,Randomised Control Study from Myheart Beat (Malaysian Health and Adolescents Longitudinal Research Team—Behavioural Epidemiology and Trial)

A healthy eating environment in the school setting is crucial to nurture the healthy eating pattern for youth. Thus, it helps to combat the obesity issue. However, the impact of healthy school environment on healthy eating habits among Asian adolescents is scarce and less clear. This clustered randomised-control study has two objectives. The first objective was to evaluate the changes in adolescents’ dietary intake after the interventions for all arms (control; healthy cooking training only; subsidization with healthy cooking training). The second objective was to compare the effect of subsidization with healthy cooking training and healthy cooking training only with the control arm on adolescents’ dietary intakes. This study consisted of 340 secondary school students aged 14 years in rural and urban Malaysia. A total of two arms of intervention and one arm of control were included. Intervention one focused on healthy cooking preparation for the canteen and convenience shop operators. Intervention two included subsidization for fruits and vegetables with a healthy cooking preparation training for the canteen and suggestions on providing healthy options to the convenience shop operators. The outcome measured was changes to dietary intake. It was measured using a three-day dietary history pre- and post-intervention. A paired-t test was used to evaluate the outcome of intervention programmes on dietary changes for all arms (control, intervention one and two). An ANCOVA test was used to investigate the effect of providing subsidization and healthy cooking preparation training to the canteen and convenience shop operators on adolescents’ dietary intakes as compared to the control arm. Overall, the reduction in energy and carbohydrates for all arms were observed. Interestingly, fat intake was significantly increased after the four-week intervention programme under healthy cooking intervention but not in the food subsidization group. When comparing between control, healthy cooking training only and subsidization with the healthy cooking training arm, there was no significant changes between arms. A robust intervention to include subsidization of healthy foods for intervention programmes at schools in a larger scale study is needed to confirm this finding.     

A Comparative Study to Evaluate the Essential Work of Fracture to Measure the Fracture Toughness of Quasi-Brittle Material

In the present work, three different woven composite laminates were fabricated using the hand lay-up method. The woven reinforcement fibres were carbon fibres (CFRP), glass fibres (GFRP-W) and (GFRP-R) in combination with epoxy resin. Then, the central notch specimen tensile test (CNT) was used to measure the fracture toughness and the corresponding surface release energy (GIC). Then, the data were compared with the essential work of fracture (we) values based on the stored energy of the body to obtain a new standard fracture toughness test for composite laminates using relatively simple techniques. In addition to an extended finite element model, XFEM was implemented over a central notch specimen geometry to obtain a satisfactory validation of the essential work of fracture concepts. Therefore, the average values of (GIC) were measured with CNT specimens 25.15 kJ/m², 32.5 kJ/m² and 20.22 kJ/m² for CFRP, GFRP-W and GFRP-R, respectively. The data are very close as the percentage error for the surface release energy measured by the two methods was 0.83, 4.6 and 5.16 for carbon, glass and random fibre composite laminates, respectively. The data for the fracture toughness of XFEM are also very close. The percentage error is 4.6, 5.25 and 2.95 for carbon, glass and random fibre composite laminates, respectively. Therefore, the fundamental work of the fracture concept is highly recommended as a fracture toughness test for composite laminates or quasi-brittle Material.     

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides.     

Incorporation of second‐tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program

BackgroundNowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non‐invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC‐MS/MS) for the evaluation of the baby''s risk of certain metabolic disorders.MethodsThis retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second‐tier tests and secondary biomarkers to improve positive predictive value (PPV).ResultsStatistical data were recorded via call interviewing in 6–8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false‐positive rate was 0.15%.ConclusionThis study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second‐tier tests and secondary biomarkers improves PPV of neonatal screening programs.     

Forecasting the Post-Pandemic Effects of the SARS-CoV-2 Virus Using the Bullwhip Phenomenon Alongside Use of Nanosensors for Disease Containment and Cure

The COVID-19 pandemic has the tendency to affect various organizational paradigm alterations, which civilization hasyet to fully comprehend. Personal to professional, individual to corporate, and across most industries, the spectrum of transformations is vast. Economically, the globe has never been more intertwined, and it has never been subjected to such widespread disruption. While many people have felt and acknowledged the pandemic’s short-term repercussions, the resultant paradigm alterations will certainly have long-term consequences with an unknown range and severity. This review paper aims at acknowledging various approaches for the prevention, detection, and diagnosis of the SARS-CoV-2 virus using nanomaterials as a base material. A nanostructure is a material classification based on dimensionality, in proportion to the characteristic diameter and surface area. Nanoparticles, quantum dots, nanowires (NW), carbon nanotubes (CNT), thin films, and nanocomposites are some examples of various dimensions, each acting as a single unit, in terms of transport capacities. Top-down and bottom-up techniques are used to fabricate nanomaterials. The large surface-to-volume ratio of nanomaterials allows one to create extremely sensitive charge or field sensors (electrical sensors, chemical sensors, explosives detection, optical sensors, and gas sensing applications). Nanowires have potential applications in information and communication technologies, low-energy lightning, and medical sensors. Carbon nanotubes have the best environmental stability, electrical characteristics, and surface-to-volume ratio of any nanomaterial, making them ideal for bio-sensing applications. Traditional commercially available techniques have focused on clinical manifestations, as well as molecular and serological detection equipment that can identify the SARS-CoV-2 virus. Scientists are expressing a lot of interest in developing a portable and easy-to-use COVID-19 detection tool. Several unique methodologies and approaches are being investigated as feasible advanced systems capable of meeting the demands. This review article attempts to emphasize the pandemic’s aftereffects, utilising the notion of the bullwhip phenomenon’s short-term and long-term effects, and it specifies the use of nanomaterials and nanosensors for detection, prevention, diagnosis, and therapy in connection to the SARS-CoV-2.     

Acute systemic exposure to silver-based nanoparticles induces hepatotoxicity and NLRP3-dependent inflammation

Nanoparticles (NPs) are increasingly being commercialized for use in biomedicine. NP toxicity following acute or chronic exposure has been described, but mechanistic insight into this process remains incomplete. Recent evidence from in vitro studies suggested a role for NLRP3 in NP cytotoxicity. In this study, we investigated the effect of systemic administration of composite inorganic NP, consisting of Ag:Cu:B (dose range 1–20?mg/kg), on the early acute (4–24?h post-exposure) and late phase response (96?h post-exposure) in normal and NLRP3-deficient mice. Our findings indicate that systemic exposure (≥2?mg/kg) was associated with acute liver injury due to preferential accumulation of NP in this organ and resulted in elevated AST, ALT and LDH levels. Moreover, within 24?h of NP administration, there was a dose-dependent increase in intraperitoneal neutrophil recruitment and upregulation in gene expression of several proinflammatory mediators, including TNF-α, IL-1β and S100A9. Histological analysis of liver tissue revealed evidence of dose-dependent hepatocyte necrosis, increase in sinusoidal Kupffer cells, lobular granulomas and foci of abscess formation which were most pronounced at 24?h following NP administration. NP deposition in the liver led to a significant upregulation in gene expression of S100A9, an endogenous danger signal recognition molecule of phagocytes, IL-1β and IL-6. The extent of proinflammatory cytokine activation and hepatotoxicity was significantly attenuated in mice deficient in the NLRP3 inflammasome, demonstrating the critical role of this innate immune system recognition receptor in the response to NP.