Rising mortality related to cardiovascular disease and prostate cancer amongst older men across the United States.

OBJECTIVE: There is a significant association between cardiovascular diseases (CVD) and prostate cancer (PCa), leading to high mortality. This study evaluates the trends in mortality associated with CVDs and PCa among older (≥ 65 years) men in the United States (US). METHODS: This analysis utilized the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). The analysis of Multiple Cause of Death Files was carried out from 1999 to 2019 to identify fatalities with CVD and PCa listed as either contributory or underlying causes of death. Crude and age-adjusted mortality rates (AAMRs) per 100,000 populations for variables such as year, race and ethnicity, and geographic regions were determined. To assess annual percent change (APC), a Joinpoint regression program was employed. RESULTS: Overall AAMR was 54.3 in 1999 and 34.6 in 2019. After a decline in AAMR from 1999 to 2015, an alarming rise in mortality was observed until 2019. Mortality rates were highest among Non-Hispanic (NH) Black and African American men (74.9). Geographically, the highest mortalities were witnessed in the West (46.4) and non-metropolitan areas (44.6). States with AAMRs ranking in the 90th percentile were Nebraska, California, North Dakota, the District of Columbia, and Mississippi. CONCLUSION: After decreasing death rates associated with CVD and PCa from 1999 to 2015, a reversal in the trend was observed from 2015 to 2019. Addressing this increase in death rates, especially among the vulnerable population, requires focused attention and targeted strategies to implement necessary safeguards in the upcoming years.

Evidence of Lone Pair Crafted Emphanisis in the Ruddlesden-Popper Halide Perovskite Cs2PbI2Cl2.

A hallmark of typical structural transformations is an increase in symmetry upon heating due to entropic favourability. However, local symmetry breaking upon warming is recently evidenced in rare crystalline phases. Termed as emphanisis, the phenomenon implores exploration of fascinating thermodynamic nuances that drive unusual structural evolutions. Here, synchrotron X-ray total scattering measurements are presented on a Ruddlesden-Popper mixed halide perovskite, Cs2PbI2Cl2, which reveal signatures of emphanisis. The genesis of symmetry lowering upon heating is traced to a lone pair-driven cooperative local structural distortion composed of thermally actuated Pb off-centring and static Cl displacement. Mapping the thermal evolution of low-lying phonon modes with inelastic neutron scattering uncovers instances of mode hardening with picosecond lifetime and an intriguing soft mode at the X-point of the Brillouin zone-features conducive to ultralow thermal transport. Together, these observations highlight the fundamental and functional implications of chemical design in engendering unconventional phenomena in crystalline materials and associated properties.

Loss of tumor suppressors promotes inflammatory tumor microenvironment and enhances LAG3+T cell mediated immune suppression.

Low response rate, treatment relapse, and resistance remain key challenges for cancer treatment with immune checkpoint blockade (ICB). Here we report that loss of specific tumor suppressors (TS) induces an inflammatory response and promotes an immune suppressive tumor microenvironment. Importantly, low expression of these TSs is associated with a higher expression of immune checkpoint inhibitory mediators. Here we identify, by using in vivo CRISPR/Cas9 based loss-of-function screening, that NF1, TSC1, and TGF-ß RII as TSs regulating immune composition. Loss of each of these three TSs leads to alterations in chromatin accessibility and enhances IL6-JAK3-STAT3/6 inflammatory pathways. This results in an immune suppressive landscape, characterized by increased numbers of LAG3+ CD8 and CD4 T cells. ICB targeting LAG3 and PD-L1 simultaneously inhibits metastatic progression in preclinical triple negative breast cancer (TNBC) mouse models of NF1-, TSC1- or TGF-ß RII- deficient tumors. Our study thus reveals a role of TSs in regulating metastasis via non-cell-autonomous modulation of the immune compartment and provides proof-of-principle for ICB targeting LAG3 for patients with NF1-, TSC1- or TGF-ß RII-inactivated cancers.

Dataset for authentication and authorization using physical layer properties in indoor environment.

The proliferation landscape of the Internet of Things (IoT) has accentuated the critical role of Authentication and Authorization (AA) mechanisms in securing interconnected devices. There is a lack of relevant datasets that can aid in building appropriate machine learning enabled security solutions focusing on authentication and authorization using physical layer characteristics. In this context, our research presents a novel dataset derived from real-world scenarios, utilizing Zigbee Zolertia Z1 nodes to capture physical layer properties in indoor environments. The dataset encompasses crucial parameters such as Received Signal Strength Indicator (RSSI), Link Quality Indicator (LQI), Device Internal Temperature, Device Battery Level, and more, providing a comprehensive foundation for advancing Machine learning enabled AA in IoT ecosystems.

External Quality Assessment Program for SARS-COV-2 Molecular Detection in Pakistan.

INTRODUCTION: Amid coronavirus disease 2019 (COVID-19) pandemic, accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for diagnosis management and breaking down transmission chains. We designed a national external quality assessment panel (EQAP) for SARS-CoV-2 molecular detection comprising working laboratories nationwide. METHODS: A molecular diagnostic EQA panel that consists of five samples for SARS CoV-2 testing was distributed to 141 public and private sector laboratories across country. These samples contain different concentrations of SARS-CoV-2 to evaluate the sensitivity of commercial kits available. RESULTS: Sensitivity among public and private sector laboratories was variable, particularly lower SARS-CoV-2 concentrations significantly increased the risk of false-negative tests, whereas Ct values of accurately tested SARS-CoV-2 specimens increased as concentration decreased. These findings highlighted that performance of used commercial kits was not significantly correlated to various extraction or PCR methods. CONCLUSION: This study highlights the need for a national external quality assessment panel (EQAP) in the country to improve the quality of the healthcare system while ensuring the accuracy and reliability of results. Furthermore, EQAPs can help laboratories meet accreditation and regulatory requirements. However, continued participation in EQAP is recommended for quality enhancement of laboratories.

Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes.

This study aimed to provide an understanding of the influence of eugenol on CYP1A2, 2C9, 2D6, and 3A4 in human liver microsomes (HLM). Specific substrate for CYP1A2, 2C9, 2D6, and 3A4 were incubated in HLM with or without eugenol. The formation of their respective metabolites was assessed with HPLC analytical methods. Eugenol at 1, 10 and 100 µM levels inhibited the activity of CYP1A2 and CYP2C9 by 23.38 %, 23.57 %, 39.80 % and 62.82 %, 63.27 %, 67.70 % respectively. While, CYP2D6 and CYP3A4 activity was decreased by 40.70 %, 45.88 %, 62.68 % and 37.41 %, 42.58 % and 67.86 % at 1, 10 and 100 µM eugenol level respectively. The IC50 value of eugenol for CYP2D6 and CYP3A4 was calculated as 11.09 ± 3.49 µM and 13.48 ± 3.86 µM respectively. Potential herb-drug interactions was noted when eugenol is administered simultaneously with medications metabolized by these enzymes, most notably CYP2C9, CYP2D6 and CYP3A4.

Photocatalytic Activity of BaAl2O4 for Water Purification.

Degradation of dyes under natural light sources is one of the most active research areas in basic science for greener technology. In this context, the photocatalytic activity of semiconductors has received massive attention in solving water treatment-related issues as these possess enormous potential for degrading organic impurities. Here, we report that barium aluminate (BaAl2O4, BAO), which has been extensively studied for photoluminescence applications, is found to be a highly potent candidate for photocatalytic activities. We have explored the degradation of dyes (meant for water purification) by using the photocatalytic properties of pure and Dy- and Yb-codoped BAO. Crystal structure, electron microscopy, and Raman analysis of the autocombustion-synthesized pure and codoped BAO samples revealed significant morphological changes such as increased particle size and stabilization of rod-like structures. UV-vis absorbance measurements confirm the presence of multiple bandgaps in the BAO samples, which is substantiated by X-ray absorption spectroscopy measurements. Photocatalytic degradation studies of methylene blue (MB) dye (with different catalyst concentrations, dopings, and MB dye concentrations) have been carried out by using BAO. The kinetics of the photocatalytic degradation measurements has been explained by the Boltzmann distribution function, and the fastest (in less than 40 min), with more than 99% degradation of MB impurity, is reported here for the first time in BAO compounds. Synthesized BAO samples show excellent cyclic stability, which is essential for their potential applications in environmental remediation. The trade-off between the enhancement of surface area and increased particle size is considered the key parameter for controlling the photocatalytic performance of the BAO catalyst after Dy and Yb codopings.

Controller-driven vector autoregression model for predicting content popularity in programmable named data networking devices.

Named Data Networking (NDN) has emerged as a promising network architecture for content delivery in edge infrastructures, primarily due to its name-based routing and integrated in-network caching. Despite these advantages, sub-optimal performance often results from the decentralized decision-making processes of caching devices. This article introduces a paradigm shift by implementing a Software Defined Networking (SDN) controller to optimize the placement of highly popular content in NDN nodes. The optimization process considers critical networking factors, including network congestion, security, topology modification, and flowrules alterations, which are essential for shaping content caching strategies. The article presents a novel content caching framework, Popularity-aware Caching in Popular Programmable NDN nodes (PaCPn). Employing a multi-variant vector autoregression (VAR) model driven by an SDN controller, PaCPn periodically updates content popularity based on time-series data, including 'request rates' and 'past popularity'. It also introduces a controller-driven heuristic algorithm that evaluates the proximity of caching points to consumers, considering factors such as 'distance cost,' 'delivery time,' and the specific 'status of the requested content'. PaCPn utilizes customized DATA named packets to ensure the source stores content with a valid residual freshness period while preventing intermediate nodes from caching it. The experimental results demonstrate significant improvements achieved by the proposed technique PaCPn compared to existing schemes. Specifically, the technique enhances cache hit rates by 20% across various metrics, including cache size, Zipf parameter, and exchanged traffic within edge infrastructure. Moreover, it reduces content retrieval delays by 28%, considering metrics such as cache capacity, the number of consumers, and network throughput. This research advances NDN content caching and offers potential optimizations for edge infrastructures.

Enhancement of microstructural and magnetic properties of high spin Mn substituted nanocrystalline Ni-Mn-Cu-Zn ferrites.

Mn-substituted Cu and Zn co-doped spinel-typed nano-crystalline ferrites having nominal composition Ni0.50-xMnxCu0.15Zn0·35Fe2O4 (x = 0.00-0.25 in 0.05 increments) have been prepared through the citric acid assisted sol-gel auto-combustion technique. From the XRD measurements, it was found that several intense peaks ensured the cubic spinel-based ferrite structure beyond the formation of any impurity peaks. The crystallite sizes varied from 20 to 28 nm for ash-burnt powders following the coalescence process that decreased the lattice defects and strain. With an increase in Mn concentration, the hopping length (LA) of the tetrahedral A-site increases, while the hopping length (LB) of the octahedral B-site decreases with enhanced lattice constant. The sintered samples' average grain sizes, as measured using the Field Emission Scanning Micrographs (FESEM), differed from around 1.40 to 5.30 µm. Incorporating Mn-ion accelerates grain growth and crystallite size with increased bulk density and reduced porosity due to heat treatment. For increasing sintering temperature along with Mn concentration, porosity drops from 42% to 3%, resulting in enhancing the magnetic induction of the prepared ferrites. The 25% Mn substituted composition displays the maximum initial permeability (µi' = 315), which is ∼7 times larger than the pristine composition. Due to the reduction of Ni content, the relative quality factor rises but the magnetic loss tangent reduces. An increased trends of µi' are accompanied by decreased resonant frequency, obeying Snoek's law. According to the experimental findings, the high spin Mn substitution in the composition causes the saturation magnetization to increase while the coercivity and Néel temperature drop with increasing grain size. Hence, the locally prepared low-cost Nano-crystalline Ni-Mn-Cu-Zn ferrites bearing excellent properties can be a good candidate for promising future applications in nanotechnology.

Pharmacokinetics of Dasatinib in Rats: a Potential Food-Drug Interaction with Naringenin.

BACKGROUND AND OBJECTIVES: The novel tyrosine kinase inhibitor (TKI) dasatinib, a multitarget inhibitor of Bcr-Abl and Src family kinases, has been licensed for the treatment of Ph+ acute lymphoblastic leukemia and chronic myeloid leukemia. Many citrus-based foods include the flavonoid naringenin, which is commonly available. Dasatinib is a Cyp3a4, P-gp, and Bcrp1 substrate, which makes it sensitive to potential food-drug interactions. The concurrent use of naringenin may change the pharmacokinetics of dasatinib, which could result in adverse effects and toxicity. The present investigation examined the impact of naringenin on the pharmacokinetics interactions of DAS and proposes a possible interaction mechanism in Wistar rats. METHODS: Rats were provided with a single oral dose of dasatinib (25 mg/kg) with or without naringenin pretreatment (150 mg/kg p.o. daily for 7 days, n = 6 in each group). Dasatinib was quantified in plasma by UHPLC MS/MS assay. Noncompartmental analysis was used to compute the pharmacokinetic parameters, and immunoblot was used to assess the protein expression in the hepatic and intestinal tissues. RESULTS: Following 7 days of naringenin pretreatment, the plasma mean concentration of dasatinib was enhanced compared with without pretreatment. In rats that were pretreated with naringenin, the pharmacokinetics of the orally administered dasatinib (25 mg/kg) was shown to be significantly different from that of dasatinib given without pretreatment (p < 0.05). There was a significant enhancement in pharmacokinetic parameters elimination half-life (T1/2), time to maximum concentration ( Tmax), maximum concentration )Cmax), area under the concentration-time curve (AUC0-t), area under the moment curve (AUMC0-∞), and mean residence time (MRT) by 28.41%, 50%, 103.54%, 72.64%, 115.08%, and 15.19%, respectively (p < 0.05) and suppression in elimination rate constant (Kel), volume of distribution (Vd), and clearance (CL) by 21.09%, 31.13%, and 46.25%, respectively, in comparison with dasatinib alone group (p < 0.05). The enhancement in dasatinib bioavailability and systemic exposure resulted from the significant inhibition of Cyp3a2, Mdr1/P-gp, and Bcrp1 expression and suppression of the dasatinib hepatic and intestinal metabolism, which enhanced the rate of dasatinib absorption and decreased its elimination. CONCLUSION: Concurrent use of naringenin-containing supplements, herbs, or foods with dasatinib may cause serious and potentially life-threatening drug interactions. Further studies are necessary to determine the clinical significance of these findings.

Evolutionary analysis of seasonal influenza A viruses in Pakistan 2020-2023.

INTRODUCTION: Influenza A viruses cause global health concerns due to their high amino acid substitution rates. They are linked to yearly seasonal epidemics and occasional pandemics. This study focused on sequencing influenza A virus strains in Pakistan. MATERIALS AND METHODS: We analyzed the genetic characteristics of influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in Pakistan from January 2020 to January 2023. Whole genome sequences from influenza A (n = 126) virus isolates were amplified and sequenced by the Oxford Nanopore (MinION) platform. RESULTS: The HA genes of influenza A(H1N1)pdm09 underwent amino acid substitutions at positions K54Q, A186T, Q189E, E224A, R259K, and K308R in sequenced samples. The HA genes of influenza A(H3N2) had amino acid substitutions at G53D, E83K, D104G, I140M, S205F, A212T, and K276R in the sequenced samples. Furthermore, the HA gene sequences of influenza A(H1N1)pdm09 in this study belonged to subclade 6B.1A.5a.2a. Similarly, the HA gene sequences of influenza A(H3N2) were classified under six subclades (3C.3a.1 and 3C.2a1b.2a [2, 2a.1, 2b, 2c, and 2a.3b]). Notably, amino acid substitutions in other gene segments of influenza A(H1N1)pdm09 and A(H3N2) were also found. CONCLUSION: These findings indicate influenza A(H1N1)pdm09 and A(H3N2) viruses co-circulated during the 2020-2023 influenza season in Pakistan. Continued surveillance is crucial for real-time monitoring of possible high-virulence variation and their relevance to existing vaccine strains.

Effect of chromium doping on the band gap tuning of titanium dioxide thin films for solar cell applications.

A simple and inexpensive spray pyrolysis deposition (SPD) approach was used to produce TiO2 and Cr (2-8) at.%-doped TiO2 thin films. To explore the morphological features of the films, FE-SEM micrographs were used and found that 6 and 8 at.% TiO2:Cr films had fibrous patterns with diameters of 0.45 and 0.78 µm, respectively, while the remainder of the films were agglomerated particles. From X-ray diffraction investigation, it was found that the TiO2 thin films had an anatase crystal phase (tetragonal) up to 6 at.% Cr doping, while an anatase-rutile mixed crystalline phase was identified for 8 at.% Cr doping. The crystallite size of the pristine TiO2 film was 35 nm, while for TiO2:Cr films, it ranges from 35 to 46 nm. The Fizeau fringes technique was employed to measure the thickness of the TiO2 film and 165 nm was found for pristine TiO2 and 164-180 nm for TiO2:Cr films. UV-visible spectroscopy was used to study optical properties such as absorbance, refractive index, optical band gap, dielectric constant, and optical conductivity. As the Cr concentration increases, the optical band gap decreases from 3.40 eV to 2.70 eV. Using the four-point probe method, it was found that the resistivity changes with temperature and is also affected by the Cr content.

Surveillance of pesticide residues in tomato and eggplant and assessment of acute and chronic health risks to the consumers in Pakistan.

Pesticide application has become a mandatory requirement of the modern agricultural system, resulting in the objectionable levels of pesticide residues in the treated food commodities and posing health threats to the consumers. This study aimed at optimization and validation of an analytical method which can be reliably applied for routine monitoring of the selected eighteen widely reported pesticides in tomato and eggplant. The principle of quick, easy, cheap, effective, rugged, and safe, i.e., QuEChERS, involving the acetate-buffered extraction followed by cleanup using the primary secondary amines (PSA) was employed. The analytical method was validated at three spiking levels (0.05, 0.01, 0.005 mg/kg) using gas chromatograph-micro electron capture detector (GC-µECD). Gas chromatograph-mass spectrometric detector (GC-MSD) was also used for confirmation and quantification using selective ion monitoring (SIM) mode. The method was applied on fresh samples of tomato (n = 33) and eggplant (n = 27) collected from local markets of Khyber Pakhtunkhwa, Pakistan, in the crop season 2020-2021. Twenty-five (76%) tomato samples and fifteen (56%) eggplant samples were found positive for one or more pesticides. Though the chronic and acute health risk assessments indicate that both of these vegetables are unlikely to pose any unacceptable health threat to their consumers, yet the risks from regular intake of pesticides-contaminated food commodities should be regularly addressed for possible protection of the public health and assurance of safe and consistent agro-trade, alike.

Microwave-Assisted Formation of Ternary Inclusion Complex of Pterostilbene.

Pterostilbene (PTS) is a naturally occurring phytoalexin. PTS displays limited water solubility, which consequently results in its diminished oral bioavailability. Therefore, a ternary inclusion complex (TIC) of PTS with ß-cyclodextrin (ßCD) in the presence of ternary substance Pluronic® F-127 (PLF) was prepared using microwave technology. The PTS-TIC was characterized by dissolution performance. Further, the prepared TIC was characterized by DSC, FTIR, NMR, XRD, and SEM analysis. Additionally, the antioxidant activity of PTS and PTS-TIC was also evaluated. Phase-solubility studies revealed that PTS's solubility in water was increased by 6.72 times when ßCD/PLF was present. In comparison with PTS, prepared PTS-TIC produced a considerable improvement in PTS release. After 1 h, 74.03 ± 4.47% of PTS was released from PTS-TIC. Outcomes of DSC, FTIR, NMR, XRD, and SEM analysis revealed that the PTS was enclosed in the ßCD cavity. In terms of antioxidant properties, the PTS-TIC formulation demonstrated superior activity compared to PTS, possibly attributed to the improved solubility of PTS resulting from the formation of TIC using microwave technology. It was concluded that microwave technology proved to be an extremely beneficial means of interacting PTS with ßCD. In addition to increasing the solubility of PTS, the findings are also expected to improve its bioavailability by increasing its solubility. As a result, this study could provide insight into potential methods for enhancing the solubility of polyphenolic substances like PTS.

Synthesis and optical properties of WS2 nanotubes with relatively small diameters.

Tungsten disulfide (WS2) nanotubes exhibit various unique properties depending on their structures, such as their diameter and wall number. The development of techniques to prepare WS2 nanotubes with the desired structure is crucial for understanding their basic properties. Notably, the synthesis and characterization of multi-walled WS2 nanotubes with small diameters are challenging. This study reports the synthesis and characterization of small-diameter WS2 nanotubes with an average inner diameter of 6 nm. The optical absorption and photoluminescence (PL) spectra of the as-prepared nanotubes indicate that a decrease in the nanotube diameter induces a red-shift in the PL, suggesting that the band gap narrowed due to a curvature effect, as suggested by theoretical calculations.

Semiconducting Transition Metal Dichalcogenide Heteronanotubes with Controlled Outer-Wall Structures.

Transition metal dichalcogenide (TMDC) nanotubes exhibit unique physical properties due to their nanotube structures. The development of techniques for synthesizing TMDC nanotubes with controlled structures is very important for their science and applications. However, structural control efforts have been made only for the homostructures of TMDC nanotubes and not for their heterostructures that provide an important platform for their two-dimensional counterparts. In this study, we synthesized heterostructures of TMDC nanotubes, MoS2/WS2 heteronanotubes, and demonstrated a technique for controlling features of their structures, such as diameters, layer numbers, and crystallinity. The diameter of the heteronanotubes could be tuned with inner nanotube templates and was reduced by using small-diameter WS2 nanotubes. The layer number and crystallinity of the MoS2 outer wall could be controlled by controlling their precursors and synthesis temperatures, resulting in the formation of high-crystallinity TMDC heteronanotubes with specific chirality. This study can expand the research of van der Waals heterostructures.

Herb-drug interaction: Effect of sinapic acid on the pharmacokinetics of dasatinib in rats.

Dasatinib (DAS) is a narrow therapeutic index drug and novel oral multitarget inhibitor of tyrosine kinase and approved for the first-line therapy for chronic myelogenous leukemia (CML) and Philadelphia chromosome (Ph + ) acute lymphoblastic leukemia (ALL). DAS, a known potent substrate of cytochrome (CYP) 3A, P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) and is subject to auto-induction. The dietary supplementation of sinapic acid (SA) or concomitant use of SA containing herbs/foods may alter the pharmacokinetics as well as pharmacodynamics of DAS, that may probably lead to potential interactions. Protein expression in rat hepatic and intestinal tissues, as well as the in vivo pharmacokinetics of DAS and the roles of CYP3 A2 and drug transporters Pgp-MDR1 and BCPR/ABCG2, suggested a likely interaction mechanism. The single dose of DAS (25 mg/kg) was given orally to rats with or without SA pretreatment (20 mg/kg p.o. per day for 7 days, n = 6). The plasma concentration of DAS was estimated by using Ultra-High-Performance Liquid Chromatography Mass spectrometry (UHPLC-MS/MS). The in vivo pharmacokinetics and protein expression study demonstrate that SA pretreatment has potential to alter the DAS pharmacokinetics. The increase in Cmax, AUC and AUMC proposes increase in bioavailability and rate of absorption via modulation of CYP3 A2, PgP-MDR1 and BCPR/ABCG2 protein expression. Thus, the concomitant use of SA alone or with DAS may cause serious life-threatening drug interactions.

Preparation and Characterization of Transethosome Formulation for the Enhanced Delivery of Sinapic Acid.

Sinapic acid (SA) is a bioactive phenolic acid; its diverse properties are its anti-inflammatory, antioxidant, anticancer, and antibacterial activities. The bioactive compound SA is poorly soluble in water. Our goal was to formulate SA-transethosomes using thin-film hydration. The prepared formulations were examined for various parameters. In addition, the optimized formulation was evaluated for surface morphology, in-vitro penetration studies across the Strat M®, and its antioxidant activity. The optimized formulation (F5) exhibited 74.36% entrapment efficacy. The vesicle size, zeta potential, and polydispersity index were found to be 111.67 nm, -7.253 mV, and 0.240, respectively. The surface morphology showed smooth and spherical vesicles of SA-transethosomes. In addition, the prepared SA-transethosomes exhibited enhanced antioxidant activity. The SA-transethosomes demonstrated considerably greater penetration across the Strat M® membrane during the study. The flux of SA and SA-transethosomes through the Strat M® membrane was 1.03 ± 0.07 µg/cm2/h and 2.93 ± 0.16 µg/cm2/h. The enhancement ratio of SA-transethosomes was 2.86 ± 0.35 compared to the control. The SA-transethosomes are flexible nano-sized vesicles and are able to penetrate the entrapped drug in a higher concentration. Hence, it was concluded that SA-transethosome-based approaches have the potential to be useful for accentuating the penetrability of SA across the skin.

Formulation and Evaluation of Plumbagin-Loaded Niosomes for an Antidiabetic Study: Optimization and In Vitro Evaluation.

Diabetes treatment requires focused administration with quality systemic circulation to determine the optimal therapeutic window. Intestinal distribution through oral administration with nanoformulation provides several benefits. Therefore, the purpose of this study is to create plumbagin enclosed within niosomes using the quality by design (QbD) strategy for efficient penetration and increased bioavailability. The formulation and optimization of plumbagin-loaded niosomes (P-Ns-Opt) involved the use of a Box-Behnken Design. The particle size (PDI) and entrapment efficiency of the optimized P-Ns-Opt were 133.6 nm, 0.150, and 75.6%, respectively. TEM, DSC, and FTIR were used to analyze the morphology and compatibility of the optimized P-Ns-Opt. Studies conducted in vitro revealed a controlled release system. P-Ns-Opt's antioxidant activity, α-amylase, and α-glucosidase were evaluated, and the results revealed a dose-dependent efficacy with 60.68 ± 0.02%,90.69 ± 2.9%, and 88.43 ± 0.89%, respectively. In summary, the created P-Ns-Opt demonstrate remarkable potential for antidiabetic activity by inhibiting oxygen radicals, α-amylase, and α-glucosidase enzymes and are, therefore, a promising drug delivery nanocarrier in the management and treatment of diabetes.

Cinnamon modulates the pharmacodynamic & pharmacokinetic of amlodipine in hypertensive rats.

The objective of this study was to investigate the effects of cinnamon on the pharmacodynamic (PD) & pharmacokinetic (PK) of amlodipine in hypertensive rats. The hypertensive control group of Wistar rats received L-NAME (40 mg/kg, daily, orally) only. The cinnamon group of rats was treated with cinnamon (200 mg/kg, daily, orally) along with L-NAME. Following 14 days treatment period, blood pressures of rats were monitored at designated intervals over 24 h utilizing a tail-cuff system for measuring blood pressure. To assess the oral PK; amlodipine was administered as a single oral dose of 1 mg/kg to rats and blood samples were collected at specified intervals over 24 h and analysed by UPLC-LC MS/MS. Synergistic decreased in rat's blood pressure was observed in presence of cinnamon + amlodipine. Simultaneous administration of cinnamon ameliorates the Cmax and AUC0-t of amlodipine, the Cmax and AUC0-t was 11.04 ± 1.01 ng/ml and 113.76 ± 5.62 ng h/ml for the cinnamon + amlodipine group as compared to 4.12 ± 0.49 ng/ml and 48.59 ± 4.28 ng h/ml for the amlodipine alone group. The study demonstrates that the use of cinnamon considerably decreases the blood pressure levels and enhances the PK parameters of amlodipine in hypertensive rats.