Pharmaceutics and Drug Design Commons^™

Phytochemical Analysis, Antioxidant And Cytotoxic Activity Of Lannea Egregia Engl. & K. Krause Stem Bark Extracts, Seide M. Akoro, Mutiat A. Omotayo, Oyinlade C. Ogundare, Stemon A. Akpovwovwo, Gbemileke P. Bello

Pharmaceutical Sciences and Research

This study investigates the phytochemical contents, antioxidants and cytotoxic activities of Lannea egregia Engl. & K. Krause stem bark extracts. Secondary metabolites were extracted using n-hexane, ethyl acetate, and ethanol by successive maceration. The concentrated extracts were subjected to preliminary phytochemical screening using standard procedures. The crude flavonoid was obtained from the plant material using Harborne’s method and then profiled using high-performance liquid chromatography (HPLC). The antioxidant activities of the plant extract were assessed using reducing power assay and DPPH scavenging activity, while the cytotoxic activity was determined using the brine shrimp lethality assay. The crude extract of n-hexane or …

Polymeric Chloroquine In Metastatic Pancreatic Cancer Therapy, Rubayat Islam Khan

Theses & Dissertations

Hydroxychloroquine (HCQ) is an established drug that has been used for the treatment of multiple diseases, including malaria, rheumatoid arthritis, and lupus erythematosus. Several recently published studies have highlighted its beneficial use in various types of cancers, and a plethora of clinical trials are currently evaluating its use in cancer therapies, wherein some of the results look promising. The preclinical studies to date suggest HCQ can work effectively in conjunction with traditional cancer treatments, as it has been shown to sensitize tumor cells to a wide range of chemotherapeutic agents. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has …

Targeted Therpeutics For Prostate Cancer, Behind The Scenes Of Psma & Cysteine Protease Trapping Mechanism, Alireza Basiri

Theses & Dissertations

In an attempt to increase the residence time of PSMA-targeted theranostics inside the prostate cancer cells and tumors, we designed and prepared a CPTA-PSMATA resembling PSMA-617 by adding a well-known cysteine protease inhibitor (E-64) to the conjugate. Lysosomal proteases, including cysteine, serine, and aspartic families of hydrolytic enzymes, are expressed in high concentrations in the lysosomes and are responsible for the catabolism of proteins inside the cell [165, 278]. We proposed that after successful internalization of the PSMA-targeted conjugates into the cells, they will be conveyed to the endolysosomes. In these endolysosomal compartments, the E-64 moiety will covalently bind to …

Editorial: Adenylyl Cyclase Isoforms As Potential Drug Targets, Tarsis F. Brust, Rennolds S. Ostrom, Val J. Watts

Pharmacy Faculty Articles and Research

Editorial on the Research Topic Adenylyl cyclase isoforms as potential drug targets

Comparison Of Cognitive Behavioral Therapy And Pharmacologic Intervention In Alcohol Use Disorder Treatment, Analily Wong, Collin Owen, Meghan Vatave

Symposium of Student Scholars

Background: Alcohol use disorder (AUD) is a condition that can result in chronic health conditions that negatively impact a person’s life. Methods to treat AUD involve cognitive behavioral therapy (CBT) and pharmacologic intervention, including disulfiram (DIS), naltrexone (NTX), and acamprosate (ACA).

Objectives: The purpose of this review is to determine the efficacy of CBT compared to pharmacologic intervention within one year of treatment in adult patients who have been diagnosed with AUD.

Methods: A reference search was conducted using various databases to locate literature. Combined keywords and Boolean operators were utilized to reveal desired articles. A total of 10 …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

The Development Of A Novel Peptide-Drug Conjugate For Treating Triple-Negative Breast Cancer, Phi-Phung Than

Pharmaceutical Sciences (MS) Theses

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor prognosis and is difficult to treat. A diagnosis of TNBC means that the three most common types of receptors known to fuel most breast cancer growth–estrogen, progesterone, and HER2– are not present in the cancer tumors. Since the tumor cells lack necessary receptors, common treatments like hormone therapies and targeted HER2 drugs are ineffective. The use of chemotherapies in treating TNBC is an effective option instead. However, chemotherapies are not selective, thus they cause severe side effects such as cardiotoxicity, myelosuppression, alopecia and gastrointestinal problems. A peptide-drug conjugate …

Hgf-Mediated C-Met Signaling In Human Corneal Epithelial Cells., Kate Tarvestad

Electronic Theses and Dissertations

Vision is often regarded as the primary sense of humans. The cornea is the main refractive tissue that permits light through to the retina, allowing a clear image. When the cornea sustains damage, it opens a pathway for infection and blindness through fibrotic processes. Healing the corneal tissue is critical for vision restoration and pain alleviation. Growth factors and their cognate receptors are currently under investigation as tools to restore proper corneal physiology. We hypothesize that manipulating the hepatocyte growth factor (HGF)/ c-Met signaling pathway is one route to promote quality corneal healing. This thesis investigates the signaling, trafficking, and …

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …

The Glycemic, Cholesterol, And Weight Effects Of L-Carnitine In Diabetes: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Jennifer Ko, Eva Y. Wong, Huyentran N. Tran, Rebecca J.C. Tran, Diana X. Cao

Pharmacy Faculty Articles and Research

Introduction

L-carnitine possibly impacts insulin sensitivity and glucose metabolism. However, its therapeutic role in diabetes is poorly understood.

Methods

A systematic review and meta-analysis were conducted using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception through June 30, 2021. Included studies evaluated the use of L-carnitine in diabetes on fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), weight, or body mass index (BMI). Weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random-effects model.

Results

Seventeen studies …

Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by …

Electromechanical Effects On Micro And Nano Particles Generated From Drug Delivery Devices And Their Implications In Flow And Deposition Efficiency, Mohammed Ali, Mark Miller

Technology Faculty Publications and Presentations

This experimental investigation was undertaken to quantify the electrostatic charge and aerodynamic size distribution of the medicinal drug particles inhaled through an in-vitro mouth-throat (MT) in order to compare the amount of drugs can be delivered to the human lung while mimicking a patient is either sitting or lying. The MT model is a cadaver-based replica cast of human oral-pharyngeal-laryngeal region. Tested drug aerosols were generated by a commercially available metered dose inhaler (MDI). The MT model was placed inside a humidity (95%) and temperature (37^oC) controlled chamber. Its mouth-inlet was positioned horizontally and vertically to simulate sitting …

Evaluation Of Pharmaceutically Compounded Oral Caffeine On The Impact Of Medication Adherence And Risk Of Readmission Among Preterm Neonates: A Single-Center Quasi-Experimental Study, Gul Ambreen, Manoj Kumar, Amin Ali, Syed Akbar Ali Shah, Syed Muzaffar Saleem, Ayesha Tahir, Muhammad Sohail Salat, Muhammad Shahzad Aslam, Kashif Hussain

Department of Biological & Biomedical Sciences

Background: Caffeine is available in an ampoule, used via parenteral and enteral routes in preterm neonates to treat apnea of prematurity (AOP) in neonates of gestational age ≥ 35-40 weeks. A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms. Pharmaceutically compounded oral caffeine (PCC) could be an appropriate alternate dosage form. The researchers aimed to determine the impact of PCC on medication-related factors influencing medication adherence (MA) and the frequency of hospital readmission with apnea (HRA) in preterm neonates.
Methods: We conducted a single-center quasi-experimental study for this quality …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

Impact Of A Multifaceted Intervention On Physicians' Knowledge, Attitudes And Practices In Relation To Pharmaceutical Incentivisation: Protocol For A Randomised Control Trial, Muhammad Naveed Noor, Mishal Khan, Afifah Rahman-Shepherd, Amna Rehana Siddiqui, Sabeen Sharif Khan, Iqbal Azam, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Introduction: In settings where the private sector constitutes a larger part of the health system, profit-gathering can take primacy over patients' well-being. In their interactions with pharmaceutical companies, private general practitioners (GPs) can experience the conflict of interest (COI), a situation whereby the impartiality of GPs' professional decision making may be influenced by secondary interests such as financial gains from prescribing specific pharmaceutical brands.
Methods and analysis: This study is a randomised controlled trial to assess the impact of a multifaceted intervention on GPs' medical practice. The study sample consists of 419 registered GPs who own/work in private clinics and …

Comparative Estimation Of The Cytotoxic Activity Of Different Parts Of Cynara Scolymus L.: Crude Extracts Versus Green Synthesized Silver Nanoparticles With Apoptotic Investigation, Shady Swidan, Amgad Khedr, Abdelaziz Farrag, Ali Nasr, Mohamed Nafie, Maged Abdel-Kader, Marwa Goda, Jihan Badr, Reda Abdelhameed

Pharmacy

Different parts of Cynara scolymus L. and their green synthesized eco-friendly silver nanoparticles (AgNPs) were screened for their cytotoxicity and apoptotic activity. Results showed that flower extract AgNPs exhibited more potent cytotoxicity compared to the normal form against PC-3 and A549 cell lines with IC50 values of 2.47 μg/mL and 1.35 μg/mL, respectively. The results were compared to doxorubicin (IC50 = 5.13 and 6.19 μg/mL, respectively). For apoptosis-induction, AgNPs prepared from the flower extract induced cell death by apoptosis by 41.34-fold change and induced necrotic cell death by 10.2-fold. Additionally, they induced total prostate apoptotic cell death by a 16.18-fold …

Silver Nanoparticles Formulation Of Flower Head’S Polyphenols Of Cynara Scolymus L.: A Promising Candidate Against Prostate (Pc-3) Cancer Cell Line Through Apoptosis Activation, Shady Swidan, Amgad Khedr, Marwa Goda, Abdelaziz Farrag, Ali Nasr, Mohamed Nafie, Maged Abdel-Kader, Jihan Badr, Reda Abdelhameed

Pharmacy

Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles …

Effectiveness And Safety Of Apixaban Vs Warfarin Among Venous Thromboembolism Patients At High-Risk Of Bleeding, Alexander T. Cohen, Janvi Sah, A. D. Dhamane, Theodore Lee, Lisa Rosenblatt, Patrick Hlavacek, Birol Emir, Allison V. Keshishian, Huseyin Yuce, Xuemei Luo

Publications and Research

This study evaluated effectiveness and safety of apixaban versus warfarin among venous thromboembolism patients at high-risk of bleeding (defined as having at least one of the following bleeding risk factors: ≥75 years; used antiplatelet, NSAIDs, or corticosteroids; had prior gastrointestinal bleeding or gastrointestinal-related conditions; late stage chronic kidney disease). Adult venous thromboembolism patients initiating apixaban or warfarin with ≥1 bleeding risk factor were identified from Medicare and four commercial claims databases in the United States. To balance characteristics between apixaban and warfarin patients, stabilized inverse probability treatment weighting was conducted. Cox proportional hazards models were used to estimate the risk …

Pharmacy Performance Based On Financial Perspective Before And During Covid-19 Pandemic : A Case Study, Eva Sartika Dasopang, Ida Fauziah, Fenny Hasanah, Desy Natalia Siahaan, Dina Yunisma Rasyida Lubis

Pharmaceutical Sciences and Research

A pharmacy, aside from being a pharmaceutical care provider is also a functioning business. Thus, in the scope of business, pharmacy performance can be analysed using liquidity, activity, and profitability ratios. This study aimed to determine the performance of Pharmacy X based on a financial perspective before and during the COVID-19 pandemic. This research is a descriptive cross-sectional study that employed data obtained from sales and purchase records. The data were analysed using financial ratio analysis methods, including liquidity, activity, and profitability ratios. This study was conducted at Pharmacy X based on the amount of prescription and non-prescription income from …

The Association Between Adherence To Oral Antihyperglycemic Agent And Hba1c Level, Indana Ayu Soraya, Rani Sauriasari, Pukovisa Prawiroharjo, Hindun Wilda Risni

Pharmaceutical Sciences and Research

Adherence to taking medication is essential for patients with chronic diseases such as Type 2 Diabetes Mellitus (T2DM). There have been many studies about the association between medication adherence and HbA1c levels, but few have used Adherence Refills and Medications Scale (ARMS) questionnaire and Proportion of Days Covered (PDC) method to measure adherence in Indonesian population. The aim of this study were to assess the association of medication adherence to HbA1c levels and compare two methods of adherence measurements. This research was conducted at Pasar Minggu Public Health Center, Jakarta using a cross-sectional design. The adherence assessment was conducted using …

Phytochemical Screening And In-Vitro Α-Glucosidase Inhibitory Activity Analysis Of Ethanol Extract Of Mangifera Quadrifida, Fadilah Fadilah

Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

Introduction: Type 2 Diabetes Mellitus (DM) is a metabolic disorder characterized by hyperglycemia caused by B cell dysfunction, insulin resistance, or both. Indonesia and worldwide have an increasing incidence that leads to a significant socio-economic burden. The effective treatment of Type 2 DM with minimal side effects is still challenging. This research aims to identify phytochemical properties in ethanol extract of Mangifera quadrifida and the effectivity as an alfa-glucosidase inhibitor beneficial to research on the treatment of type 2 DM.

Method: Mangifera quadrifida was extracted by ethanol as solvent. The phytochemical analysis is conducted by phytochemical screening methods and …

Quality By Design Based Optimization Of Anti-Inflammatory Nanoemulgels For Local Treatment Of Burn Wounds, Leah Dickey

Electronic Theses and Dissertations

Burns are some of the most traumatizing and damaging skin injuries, with the potential of causing extensive internal damage that increases the risk of chronic wound development. Oral and topical analgesics in combination with antibiotics can provide temporary relief and improve wound healing progress for both mild and severe burns. However, recurrent systemic exposure to pain relievers and antibiotics has been associated with adverse side effects including nausea, drowsiness, abdominal pain, etc., and increased risk of new infections or even ulcers. Local and targeted drug delivery systems, such as nanomedicine, have gained attention as potentially more effective alternatives to improve …

The Development And In Vivo Immunologic Assessment Of Biodegradable Microparticles Incorporating Cpdi-02 And Mucosal Protein Vaccine, Jacob E. Parriott

Theses & Dissertations

Encapsulation in biodegradable microparticles (MPs) is a promising approach to increase the efficacy of intranasally administered protein vaccines. The generation of long-lived adaptive immune responses against encapsulated protein vaccines, however, requires the incorporation of a suitable mucosal adjuvant. CPDI-02—a complement peptide-derived immunostimulant that selectively activates dendritic cells and macrophages over neutrophils while minimizing the inflammatory side effects of parent C5a—has previously been incorporated into both systemic and mucosal vaccine formulations via direct conjugation to chemical moieties, peptides, proteins, inactivated pathogens, and the surface of biodegradable particles, to enhance Th1-biased cellular immune responses. The effect of CPDI-02 surface conjugation to MPs …

Perturbation Modeling For Molecular Design Of Protein Tyrosine Kinase Inhibitors Using Unsupervised Machine Learning, Keerthi Krishnan

Computational and Data Sciences (MS) Theses

The field of computational drug discovery and development has grown, with the aid of new computational tools for novel molecule discovery. In specific, generative deep learning models have excelled as tools to aid in navigating the large space of known molecules and in the creation of new molecules. These models are fed various representations of molecules as inputs and learn to perform a variety of things, such as the optimization of these molecules towards a targeted property. Ultimately, these generative learning models allow us to build bridges between chemical and continuous spaces to understand the compromise between invoking small incremental …

Effects Of Nnos Inhibitors On Melanoma-Induced Immunosuppression, Kate Alison Lozada

Pharmaceutical Sciences (MS) Theses

The incidence of cutaneous melanoma (CM) rises despite advances in immunotherapy and targeted therapy. Studies have shown that interferon-gamma (IFN-γ), a pro-tumorigenic cytokine in CM, induces the expression of programmed death-ligand 1 (PD-L1), leading to the escape of melanoma cells from immunosurveillance. Our previous study suggests that neuronal nitric oxide synthase (nNOS)-mediated nitric oxide (NO) signaling is crucial for melanoma progression and forms a mechanistic rationale behind nNOS inhibition as a novel treatment strategy for CM. An additional study demonstrated that IFN-γ interacts with nNOS signaling in melanoma and novel nNOS inhibitors (nNOSi) effectively diminished the induction of PD-L1 post …

Cyclic And Linear Cell-Penetarating Peptides Composed Of Tryptophan (Ww) And Arginine (Rr) Residues As Molecular Transporters, Lois Kim

Pharmaceutical Sciences (MS) Theses

The cell membrane has polar and negative charged characteristics and separates the inside of cells from the outside environment, and only allows small molecules to go into the cell to protect them from toxic substances. However, cell membrane characteristics make it difficult for polar and negatively-charged molecules to interact and penetrate the membrane. The delivery of cell impermeable compounds, such as phosphopeptides and siRNA, across the cell membrane remains a challenge. Previous studies in Dr. Parang’s laboratory have shown that cyclic peptides composed of tryptophan (W) and arginine (R) amino acids [WR]₅ have higher cellular uptake than the corresponding …

Evaluation Of Residual Antibacterial Effects On Canine Skin Surface And Hairs Following Treatment With Five Commercial Mousse Products Against Staphylococcus Pseudintermedius In Vitro, Chi-Yen Wu

LSU Master's Theses

Topical products are essential treatments for canine superficial bacterial folliculitis. However, studies for commercial products typically evaluate antibacterial effects on hairs rather than the skin surface. In addition, the interference from the hair length has not been evaluated in these studies. Therefore, the study objective for this study was to evaluate the residual antibacterial effects of five mousse products, (1) 2% chlorhexidine and 2% miconazole, (2) 0.05% phytosphingosine, (3) 2% salicylic acid and 10% ethyl lactate, (4) 3% chlorhexidine and 0.5% climbazole, and (5) 2% chlorhexidine and 1% ketoconazole on both the skin surface and hairs in both short- and …

Analyzing Factors Impacting Time To Full Approval Of Innovative Drugs Via An Accelerated Approval Pathway In The United States, Eleanor Panico

Seton Hall University Dissertations and Theses (ETDs)

Background and purpose of study: Pharmaceutical drugs are commonly used to treat various ailments and the pharmaceutical industry is increasingly leveraging expedited pathways to market, like the FDA’s accelerated approval pathway. Thus, these pathways are becoming more prevalent and thus more scrutinized for reliability. A consequence from this increased utilization is observed variability in time to reach full approval from the point accelerated approval was received. Variables that may impact time and ability to reach full approval should be further investigated. The purpose of this study was to explore, identify and predict variables that may influence time from accelerated approval …

Medication Therapy Management Implementation In Conjunction With A Rural Health Clinic In Minnesota: A Cqi Impact On Diabetes Metrics, Abigail Sirek Pharmd

Theses and Dissertations

The purpose of this continuous quality improvement project was to implement a pharmacist-led Medication Therapy Management (MTM) clinic in rural, central Minnesota and assess the impact on patients’ healthcare over a six-month period. Patients were identified through the clinic’s diabetes registry, which included patients 18 through 75 years old with a diagnosis of diabetes not meeting all five D5 goals, as recommended by the Minnesota Community Measurements, independently referred by the provider, or be identified by their insurance company as a patient that would benefit from an MTM visit. The D5 focuses on blood pressure and blood sugar control, appropriate …

Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib

Theses and Dissertations (ETD)

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …