The anthraquinone derivative KA-4s reduces energy metabolism and enhances the sensitivity of ovarian cancer cells to cisplatin.

Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP) is a first-line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK-mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA-4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA-4s inhibited the proliferation of ovarian cancer cells. The combination of KA-4s with DDP effectively promoted drug-resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA-4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA-4s reduce drug resistance. KA-4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism-related proteins GLUT1 and GLUT4; the lipid metabolism-related proteins SREBP1 and SCD1; and the drug resistance-related proteins P-gp, MRP1, and LRP. The inhibitory effect of KA-4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY-876. KA-4s combined with DDP significantly increased the expression of p-AMPK and reduced the expression of P-gp. In a xenograft model of ovarian cancer, treatment with KA-4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA-4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.

Strongly active and environmentally friendly WO3/C3N4 photocatalysts for converting cyclohexane to cyclohexanone under ambient conditions.

C-H bond activation under mild conditions remains a great challenge in the chemical industry, while catalytic cyclohexane oxidation is inefficient and often requires organic solvents and strong oxidants. This study constructed a C3N4/WO3 Z-type heterojunction catalyst to efficiently convert cyclohexane into cyclohexanone and cyclohexanol (KA oil) through aqueous phase oxidation by O2 under visible light irradiation. With strong redox performance and high photogenerated carrier separation ability, the proposed composite catalyst can produce the key active species for cyclohexane oxidation in the H2O-O2 system. The reaction mechanism was clarified through experiment and DFT theory calculation. Cyclohexane was converted into cyclohexyl radical under the action of ·OH, and ·O2- converted most products into cyclohexanone. The catalyst can be recycled under optimized process conditions while reaching a KA oil yield of 139.73 µmol g-1 h-1 and a selectivity of 93.1%.

Femoral cartilage thickness measured on MRI varies among individuals: Time to deepen one of the principles of kinematic alignment in total knee arthroplasty. A systematic review.

PURPOSE: Kinematically aligned total knee arthroplasty (KA TKA), as a pure resurfacing procedure, is based on matching implant thickness with bone cut and kerf thickness, plus cartilage wear. However, the assumption of a consistent 2 mm femoral cartilage thickness remains unproven. This study aimed to systematically review the available literature concerning magnetic resonance imaging (MRI) assessment of femoral cartilage thickness in non-arthritic patients. Our hypothesis was that cartilage thickness values would vary significantly among individuals, thereby challenging the established KA paradigm of 'one-cartilage-fits-all'. METHODS: Systematic literature searches (Pubmed, Scopus and Cochrane Library) followed PRISMA guidelines. English-language studies assessing distal and posterior femoral cartilage thickness using MRI in non-arthritic adults were included. Studies lacking numerical cartilage thickness data, involving post-operative MRI, considering total femoro-tibial cartilage thickness, or failing to specify the compartment of the knee being studied were excluded. RESULTS: Overall, 27 studies comprising 8170 MRIs were analysed. Weighted mean femoral cartilage thicknesses were: 2.05 ± 0.62 mm (mean range 1.06-2.6) for the distal medial condyle, 1.95 ± 0.4 mm (mean range 1.15-2.5) for the distal lateral condyle, 2.44 ± 0.5 mm (mean range 1.37-2.6) for the posterior medial condyle and 2.27 ± 0.38 mm (mean range 1.48-2.5) for the posterior lateral condyle. DISCUSSION: Femoral cartilage thickness varies significantly across patients. In KA TKA, relying on a fixed thickness of 2 mm may jeopardize the accurate restoration of individual anatomy, leading to errors in implant coronal and rotational alignment. An intraoperative assessment of cartilage thickness may be advisable to express the KA philosophy at its full potential. LEVEL OF EVIDENCE: Level IV.

Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid.

BACKGROUND: The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness. OBJECTIVE: We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study. METHOD: The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system. RESULT: The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank. CONCLUSION: Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.

A Compact Linear Microstrip Patch Beamformer Antenna Array for Millimeter-Wave Future Communication.

5/6G is anticipated to address challenges such as low data speed and high latency in current cellular networks, particularly as the number of users overwhelms 4G and LTE capabilities. This paper proposes a microstrip patch antenna array comprising six radiating patches and utilizing a microstrip line feeding technique to facilitate the compact design crucial for 5G implementation. ROGER 3003, chosen for its advanced and environmentally friendly features, serves as the dielectric material, ensuring suitability for 5G and B5G applications. The designed antenna, evaluated at a resonating frequency of 28.8 GHz with a -10 dB impedance bandwidth of 1 GHz, offers a high gain of 9.19 dBi. Its compact array, cost-effectiveness, and broad impedance and radiation coverage position it as a viable candidate for 5G and future communication applications.

Silver Complex Bearing N-Heterocyclic Carbene Bidentate Chelating Ligand as an Efficient Catalyst in Solvent-Free KA2 Coupling.

We report a synthesis of silver complexes bearing chelating bidentate N-heterocyclic carbene, with various substitutions at the terminal positions of the imidazole moiety of the NHC units. The long aliphatic substituents proved to be beneficial in terms of the synthetic efficiency of the complexes, compared to previously reported methyl substitution. The complexes demonstrated excellent suitability for the KA2 coupling reaction, providing quaternary carbon-containing propargylic amines in yields up to 95 %, under solvent-free conditions. The method showed high tolerance for a wide range of substrates, including naturally occurring ketones, underscoring its practicality. To our knowledge, this represents the first use of a well-defined silver species in KA2 coupling, marking an advancement in the field.

Limitations of the knee society score in kinematically aligned total knee arthroplasty.

Purpose: The Knee Society Scoring System (KSS) is a frequently used outcome score which quantifies functional patients' outcomes before and after total knee arthroplasty (TKA). Several problems arise when trying to implement KSS for obtaining postoperative outcomes after more personalised aligned TKAs. Scoring for valgus femorotibial angle (FTA) intervals outside moderate ranges is often poorly explained, the specific version of KSS used for outcome collection is frequently unclear and the exact measuring methods are typically not described in the literature. The aims of this systematic review were to investigate the latest user practice, the application of KSS and its limitations after kinematically aligned (KA) TKA. Methods: A systematic literature search following PRISMA guidelines was conducted on PubMed, Embase, Medline and Scopus to identify potentially relevant articles for this review, published from the beginning of January 2013 until the end of January 2023. Broad Mesh terms such as 'kinematic alignment', 'total knee arthroplasty' and 'knee society score' were used for building search strategy in each database accordingly. Articles reporting postoperative values of the objective surgeon-assessed KSS after KA TKA or KA and mechanically aligned TKA were included. For assessing included randomised control trials (RCTs), an Agency for Healthcare Research and Quality's design-specific scale for assessing RCTs was used. The non-RCTs were assessed by using the Joanna Briggs Institute Critical Appraisal Tool. The Ottawa-Newcastle Score system was also used. Studies were additionally evaluated for their radiological methodology by using a five-question checklist (Radiological Assessment Qualit criteria). Results: The initial search identified 167 studies, of which 129 were considered for screening. Ten studies reporting outcomes after KA TKA did not use the objective surgeon-assessed part of KSS for clinical outcome measurement, and 30 studies reporting outcomes after KA TKA did not use KSS at all for clinical and/or functional outcomes. From the 10 included studies, only six have used the latest KSS score (2011), the rest using its 1989 variant; and out of these six studies, only two presented values of the FTA, which is needed for calculating the KSS's 'alignment' subcomponent, the rest presenting hip-knee-ankle angle (HKA) values. Additionally, when converting these HKA values to FTA intervals, the authors of this systematic review found that KA TKA FTA intervals display limits, which tend to be outside the 'well-scored' KSS anatomical alignment interval. Conclusion: The inconsistent and nonstandardised use of the surgeon-assessed KSS across studies reviewed compromises assessment reliability and patient outcome scores. To enhance precision and comparability, it is crucial to standardise the KSS application, incorporating personalised alignment strategies for more accurate patient evaluations. Level of Evidence: Level III.

Morphological observation, molecular identification and evolutionary analysis of Hydatigera kamiyai found in Neodon fuscus from the Qinghai-Tibetan plateau.

Hydatigera kamiyai (H. kamiyai) is a new species within Hydatigera that has recently been resurrected. Voles and cats are hosts of H. kamiyai and have a certain impact on its health and economy. Moreover, the Qinghai-Tibetan plateau (QTP) is a research hotspot representing Earth's biodiversity, as its unique geographical environment and climatic conditions support the growth of a variety of mammals and provide favorable conditions for various parasites to complete their life history. The aim of this study was to reveal the phylogenetic relationships and divergence times of H. kamiyai strains isolated from Neodon fuscus on the QTP using morphological and molecular methods. In this study, we morphologically observed H. kamiyai and sequenced the whole mitochondrial genome. Then, we constructed phylogenetic trees with the maximum likelihood (ML) and Bayesian inference (BI) methods. The GTR alternative model was selected for divergence time analysis. These data demonstrated that the results were consistent with the general morphological characteristics of Hydatigera. The whole genome of H. kamiyai was 13,822 bp in size, and the A + T content (73%) was greater than the G + C content (27%). The Ka/Ks values were all <1, indicating that all 13 protein-coding genes (13 PCGs) underwent purifying selection during the process of evolution. The phylogenetic tree generated based on the 13 PCGs, cytochrom oxidase subunit I (COI), 18S rRNA and 28S rRNA revealed close phylogenetic relationships between H. kamiyai and Hydatigera, with high node support for the relationship. The divergence time based on 13 PCGs indicated that H. kamiyai diverged approximately 11.3 million years ago (Mya) in the Miocene. Interestingly, it diverged later than the period of rapid uplift in the QTP. We also speculated that H. kamiyai differentiation was caused by host differentiation due to the favorable living conditions brought about by the uplift of the QTP. As there have been relatively few investigations on the mitochondrial genome of H. kamiyai, our study could provide factual support for further studies of H. kamiyai on the QTP. We also emphasized the importance of further studies of its hosts, Neodon fuscus and cats, which will be important for further understanding the life cycle of H. kamiyai.

Synaptic effects of xenon on NMDA receptor-mediated response in rat spinal neuron.

To investigate the precise mechanism of xenon (Xe), pharmacologically isolated AMPA/KA and NMDA receptor-mediated spontaneous (s) and evoked (e) excitatory postsynaptic currents (s/eEPSCAMPA/KA and s/eEPSCNMDA) were recorded from mechanically isolated single spinal sacral dorsal commissural nucleus (SDCN) neurons attached with glutamatergic nerve endings (boutons) using conventional whole-cell patch-clamp technique. We analysed kinetic properties of both s/eEPSCAMPA/KA and s/eEPSCNMDA by focal single- and/or paired-pulse electrical stimulation to compare them. The s/eEPSCNMDA showed smaller amplitude, slower rise time, and slower 1/e decay time constant (τDecay) than those of s/eEPSCAMPA/KA. We previously examined how Xe modulates s/eEPSCAMPA/KA, therefore, examined the effects on s/eEPSCNMDA in the present study. Xe decreased the frequency and amplitude of sEPSCNMDA, and decreased the amplitude but increased the failure rate and paired-pulse ratio of eEPSCNMDA without affecting their τDecay. It was concluded that Xe might suppress NMDA receptor-mediated synaptic transmission via both presynaptic and postsynaptic mechanisms.

Superionic Conduction in K3SbS4 Enabled by Cl-Modified Anion Lattice.

All-solid-state potassium batteries emerge as promising alternatives to lithium batteries, leveraging their high natural abundance and cost-effectiveness. Developing potassium solid electrolytes (SEs) with high room-temperature ionic conductivity is critical for realizing efficient potassium batteries. In this study, we present the synthesis of K2.98Sb0.91S3.53Cl0.47, showcasing a room-temperature ionic conductivity of 0.32 mS/cm and a low activation energy of 0.26 eV. This represents an increase of over two orders of magnitude compared to the parent compound K3SbS4, marking the highest reported ionic conductivity for non-oxide potassium SEs. Solid-state 39K magic-angle-spinning nuclear magnetic resonance on K2.98Sb0.91S3.53Cl0.47 reveals an increased population of mobile K+ ions with fast dynamics. Ab initio molecular dynamics (AIMD) simulations further confirm a delocalized K+ density and significantly enhanced K+ diffusion. This work demonstrates diversification of the anion sublattice as an effective approach to enhance ion transport and highlights K2.98Sb0.91S3.53Cl0.47 as a promising SE for all-solid-state potassium batteries.

A gm/ID-Based Low-Power LNA for Ka-Band Applications.

This article presents the design of a low-power low noise amplifier (LNA) implemented in 45 nm silicon-on-insulator (SOI) technology using the gm/ID methodology. The Ka-band LNA achieves a very low power consumption of only 1.98 mW andis the first time the gm/ID approach is applied at such a high frequency. The circuit is suitable for Ka-band applications with a central frequency of 28 GHz, as the circuit is intended to operate in the n257 frequency band defined by the 3GPP 5G new radio (NR) specification. The proposed cascode LNA uses the gm/ID methodology in an RF/MW scenario to exploit the advantages of moderate inversion region operation. The circuit occupies a total area of 1.23 mm2 excluding pads and draws 1.98 mW from a DC supply of 0.9 V. Post-layout simulation results reveal a total gain of 11.4 dB, a noise figure (NF) of 3.8 dB, and an input return loss (IRL) better than 12 dB. Compared to conventional circuits, this design obtains a remarkable figure of merit (FoM) as the LNA reports a gain and NF in line with other approaches with very low power consumption.

Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis.

Background: Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear. Objective: This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets. Methods: We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells. Results: The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells. Conclusion: We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

Inhibition of the RPS6KA1/FoxO1 signaling axis by hydroxycitric acid attenuates HFD-induced obesity through MCE suppression.

BACKGROUND: Because obesity is associated with a hyperplasia-mediated increase in adipose tissue, inhibiting cell proliferation during mitotic clonal expansion (MCE) is a leading strategy for preventing obesity. Although (-)-hydroxycitric acid (HCA) is used to control obesity, the molecular mechanisms underlying its effects on MCE are poorly understood. PURPOSE: This study aimed to investigate the potential effects of HCA on MCE and underlying molecular mechanisms affecting adipogenesis and obesity improvements. METHODS: Preadipocyte cell line, 3T3-L1, were treated with HCA; oil red O, cell proliferation, cell cycle, and related alterations in signaling pathways were examined. High-fat diet (HFD)-fed mice were administered HCA for 12 weeks; body and adipose tissues weights were evaluated, and the regulation of signaling pathways in epidydimal white adipose tissue were examined in vivo. RESULTS: Here, we report that during MCE, HCA attenuates the proliferation of the preadipocyte cell line, 3T3-L1, by arresting the cell cycle at the G0/G1 phase. In addition, HCA markedly inhibits Forkhead Box O1 (FoxO1) phosphorylation, thereby inducing the expression of cyclin-dependent kinase inhibitor 1B and suppressing the levels of cyclin-dependent kinase 2, cyclin E1, proliferating cell nuclear antigen, and phosphorylated retinoblastoma. Importantly, we found that ribosomal protein S6 kinase A1 (RPS6KA1) influences HCA-mediated inactivation of FoxO1 and its nuclear exclusion. An animal model of obesity revealed that HCA reduced high-fat diet-induced obesity by suppressing adipocyte numbers as well as epididymal and mesenteric white adipose tissue mass, which is attributed to the regulation of RPS6KA1, FoxO1, CDKN1B and PCNA that had been consistently identified in vitro. CONCLUSIONS: These findings provide novel insights into the mechanism by which HCA regulates adipogenesis and highlight the RPS6KA1/FoxO1 signaling axis as a therapeutic target for obesity.

Refining taxonomic identification of microalgae through molecular and genetic evolution: a case study of Prorocentrum lima and Prorocentrum arenarium.

Species delimitation based on lineage definition has become increasingly popular. However, these methods have been limited, especially for species that lack genomic data and are morphologically similar. The trickiest part for the species identification is that the interspecific and intraspecific boundaries are vague. Taking Prorocentrum (Dinophyta) as an example, analysis of cell morphology, growth, and toxin synthesis in both species of P. lima and P. arenarium does not provide a reliable basis for species delineation. However, through phylogenetic and genetic distance analyses of their ITS and LSU sequences, establishment of evolutionary tree based on orthologous gene sequences, and combining the results of automatic barcode gap discovery and Poisson tree processes models, it was sustained that P. arenarium does not belong to the P. lima complex and should be considered as an independent species. Interspecies genetic evolution analysis revealed that P. lima and P. arenarium may contribute to evolutionary direction that favors combating reverse environmental factors. In P. lima, viral invasion may be one of the reasons for its large genome size. In the study, P. lima complex has been selected as an example to enhance the taxonomic identification of microalgae through molecular and genetic evolution, offering valuable insights into refining taxonomic identification and promoting microbial biodiversity research in other species.IMPORTANCEMicroalgae, especially the species known as Prorocentrum, have received significant attention due to their ability to trigger harmful algal blooms and produce toxins. However, the boundaries between species and within species are ambiguous. Clear and comprehensive species delineation indicates that Prorocentrum arenarium should be considered as an independent species, separate from the Prorocentrum lima complex. Improving the classification and identification of microalgae through molecular and genetic evolution will provide reference points for other cryptic species. Prorocentrum occupy multiple ecological niches in marine environments, and studying their evolutionary direction contributes to understanding their ecological adaptations and community succession.

Synthesis of propargylamine: pioneering a green path with non-conventional KA2 coupling approach.

The KA2 coupling reaction is a well-explored and versatile method for forming C-C bonds in synthetic chemistry. It is composed of ketone, amine, and alkyne, which play a major role in the synthesis of propargylamines, known for their diverse biological activities and are used in treating neurogenetical disorders. The KA2 coupling is highly challenging due to the low reactivity of ketimines toward nucleophilic attacks with metal acetylide intermediates formed by activating the C-H bond of the alkyne. Despite predominant studies conducted on thermal conditions for KA2 coupling reactions, green and sustainable approaches like non-conventional methods still have a lot to achieve. This review article provides a comprehensive introduction to the non-conventional approach in the KA2 coupling reaction, outlining its mechanisms and exploring future aspects.

Smartphone-assimilated colorimetric sensor for sub-nanomolar emamectin detection via KA30 capped silver nanoparticles in food, bio-fluids and water samples.

In this report, we firstly synthesized nitro calix [4] resorcinarene compound (referred as KA30) and characterized it though proton (1H) nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and Fourier Transform Infra-red (FTIR) spectroscopy. KA30 was applied as functionalizing agent for the formation of silver nanoparticles (KA30-AgNPs). These NPs were confirmed as highly selective and extremely sensitive colorimetric sensor for ultra-low level detection of emamectin (EMA) as a novel report. Significant aspect of the sensor is its unique detection range between 0.0005 and 29.5 µM via color change from yellow to colorless with hypochromic-bathochromic shift exhibiting limit of detection (LOD) and limit of quantification (LOQ) as 0.12 nM and 0.4 nM respectively. The sensor was applied to colorimetrically and optically detect EMA in real samples of serum, urine and food. The sensor was further allied with smartphone for real-time, and on-site detection of EMA and results were validated through UPLC.

[Effect of Reducing Fluoroscopy Pulse Rates on Visibility of Devices and Radiation Dose in Percutaneous Coronary Intervention].

The goal of our study was to clarify the effect of low pulse rate fluoroscopy applying in percutaneous coronary intervention (PCI) on devices' visibility and radiation dose. Four types of fluoroscopy conditions combined with two pulse rates (7.5 and 15 pulses/s) and two types of adaptive temporal filters (ATFs) (weak and strong) were used. Samples for visibility evaluation were acquired with moving phantom and devices such as stent, balloon, and guidewire. Trailing artifacts and the visibility of stent were evaluated by Scheffe's method of paired comparisons. Incident air kerma (Ka,r) and kerma area product (PKA) in the clinic were obtained under two fluoroscopic pulse rate conditions (7.5 and 15 pulses/s). As a result, in 7.5 pulses/s fluoroscopy, trailing artifacts were decreased by using weak ATF with the median value of PKA and Ka,r reduced by about 50%, but stent visibility was decreased compared to 15 pulses/s. Therefore, a combination of 7.5 pulses/s fluoroscopy and suitable ATF can bring dose reduction with avoiding trailing artifacts, but dose per pulse should be adjusted to maintain the stent visibility.

An audit of patient radiation doses during interventional cardiology procedures in Uttarakhand, India, and establishment of local diagnostic reference levels.

The objective of this study was to investigate patient radiation doses by a dose audit of three common interventional cardiology (IC) procedures: coronary angiography (CA), percutaneous transluminal coronary angioplasty (PTCA) and CA-PTCA procedures performed in IC centres in the Uttarakhand state of India, for the establishment of local diagnostic reference levels (DRLs) and the estimation of average effective dose (Eav) for these procedures. For each procedure, the values of kerma-area product (PKA), reference air kerma (Ka,r), fluoroscopy time (FT) and the number of cine images were recorded from 1233 CA, 458 PTCA and 736 CA-PTCA procedures performed over a 12-month period at 13 IC centres of the state. From the recorded dose data, 0.6%, 1.53% and 7.9% patients were identified to have exceeded the PKA trigger level of 500 Gy cm2 for possible skin injury for CA, PTCA and CA-PTCA procedures, respectively. The 3rd quartile of the distribution of the recorded PKA values for each type of procedure was calculated to estimate local DRL values. The estimated values of DRLs and Eav were 37, 153 and 224 Gy cm2, and 6.72, 23.97 and 34.79 mSv for CA, PTCA and CA-PTCA procedures, respectively. For about 77% of the surveyed centres, the recorded patient doses were in agreement with the international standards. The local DRLs proposed in this study may be used to achieve patient dose optimization during IC procedures and the obtained patient dose data may also be archived into national dose database for the establishment of national DRLs.

Clinical Analysis and in Vitro Correlation of BCRP-Mediated Drug-Drug Interaction in the Gastrointestinal Tract.

Breast cancer resistance protein (BCRP) is a drug efflux transporter expressed on the epithelial cells of the small intestine and on the lateral membrane of the bile duct in the liver; and is involved in the efflux of substrate drugs into the gastrointestinal lumen and secretion into bile. Recently, the area under the plasma concentration-time curve (AUC) of rosuvastatin (ROS), a BCRP substrate drug, has been reported to be increased by BCRP inhibitors, and BCRP-mediated drug-drug interaction (DDI) has attracted attention. In this study, we performed a ROS uptake study using human colon cancer-derived Caco-2 cells and confirmed that BCRP inhibitors significantly increased the intracellular accumulation of ROS. The correlation between the cell to medium (C/M) ratio of ROS obtained by the in vitro study and the absorption rate constant (ka) ratio obtained by clinical analysis was examined, and a significant positive correlation was observed. Therefore, it is suggested that the in vitro study using Caco-2 cells could be used to quantitatively estimate BCRP-mediated DDI with ROS in the gastrointestinal tract.