Effectiveness Of Drugs Research Articles

A systematic investigation of solution and technological parameters for the fabrication and characterization of poly (vinyl alcohol–chitosan electrospun nanofibers

AbstractNanomaterials, particularly nanofibers are demonstrating exceptional potential for medical applications considered as promising systems for the integration of drug molecules, providing an enhancement of drug effectiveness and safety, while reducing drug side effects. Nanofibers based on two polymeric matrices poly(vinyl alcohol) (PVA) and chitosan (CS) have been demonstrated to be safe and promising materials for the drug integration and targeted drug delivery. This article studied the factors influencing on the fabrication and properties of PVA–CS nanofibers, including the impact of solution components on solution structure, rheological properties, electrospinning technology parameters, as well as the structure and thermomechanical properties of the obtained nanofibers have been investigated in details. The increasing of acetic acid concentration has the effect of pH lowering as well as electrical conductivity while heightening its viscosity. The pH, conductivity, and viscosity values of the solution rises as the CS concentration increases. Based on the Hildebrand‐Scatchard solubility theory, calculated Teas diagrams that account intermolecular interactions allow to predict low‐defect nanofibers based on PVA–CS in binary solvent systems with a greater concentration of hydrogen bonds. The optimal solution content and electrospinning parameters were determined. Infrared spectroscopy confirmed that the two polymer materials have a good interaction and the acetic acid was completely separated from the PVA–CS nanofibers. The XRD spectrum reveals that the crystal lattice parameters of the nanofibers change according to the polymer ratio. The polymers ratio also influence on the thermal and tensile properties. Such biosafe polymer materials may be considered as the promising drug delivery systems with the targeted mode of action.

The Influence of CYP2C19 Gene Polymorphism on Selective Serotonin Reuptake Inhibitors In Patients with Major Depressive Disorder: A Pharmacogenetic Prospecting Approach

Major Depressive Disorder (MDD) is a chronic disorder characterized by at least a two-week-long major depressive episode. Selective Serotonin Reuptake Inhibitors (SSRIs) remain the primary prescribed antidepressants to treat MDD. However, SSRIs themselves are found to be ineffective in some individuals or may even lead to adverse side effects. These variable responses have been linked to the drug being metabolized by CYP2C19, which exhibited various polymorphisms. Understanding how gene polymorphism affects drug metabolism is essential since these insights can revolutionize clinical practice, allowing for more precise and personalized treatment approaches that optimize efficacy while minimizing side effects. This issue is particularly pertinent in Indonesia, where research in this area lags behind the pressing need for such studies. In this review, the impact of CYP2C19 polymorphism on the effectiveness of SSRI class drugs, namely citalopram, escitalopram, and sertraline, are explored. Nine relevant articles related to the topic have been studied in Japan, China, Turkey, Russia, Scandinavia, and Australia. The results concluded that CYP2C19 polymorphism can influence the metabolism of SSRIs (citalopram, escitalopram, and sertraline) due to its variability in enzyme activities, which includes both loss-of-function (*2, *3) and gain-of-function (*17) polymorphisms. Consequently, these genetic variations can lead to significant changes in drug efficacy and safety changes within individual patients. This review sheds light on the importance of considering genetic factors when prescribing SSRIs for MDD in the future treatment strategies.

Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response.

Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney's blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.

Comparative evaluation of hesperetin-loaded graphene oxide nanosheets (Hsp-GO) as a drug delivery system for colon cancer: synthesis and anticancer efficiency assessment.

Graphene oxide nanosheets (GONS) are recognized for their role in enhancing drug delivery and effectiveness in cancer treatment. With colon cancer being a prevalent global issue and the significant side effects associated with chemotherapy, the primary treatment for colon cancer alongside surgery, there is a critical need for novel therapeutic strategies to support patients in combating this disease. Hesperetin (HSP), a natural compound found in specific fruits, exhibits anti-cancer properties. The aim of this study is to investigate the effect of GONS on the LS174t colon cancer cell line. In this study, an anti-cancer nano-drug was synthesized by creating a hesperetin-graphene oxide nanocomposite (Hsp-GO), which was subsequently evaluated for its efficacy through in vitro cell toxicity assays. Three systems were investigated: HSP, GONS, and HSP-loaded GONS, to determine their cytotoxic and pro-apoptotic impacts on the LS174t colon cancer cell line, along with assessing the expression of BAX and BCL2. The morphology and properties of both GO and Hsp-GO were examined using scanning electron microscopy (SEM), X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). The Hsp-GO nanocomposite displayed potent cytotoxic and pro-apoptotic effects on LS174t colon cancer cells, outperforming individual treatments with HSP or GONS. Cell viability assays showed a significant decrease in cell viability with Hsp-GO treatment. Analysis of BAX and BCL2 expression revealed elevated BAX and reduced BCL2 levels in Hsp-GO treated cells, indicating enhanced apoptotic activity. Morphological analysis confirmed successful Hsp-GO synthesis, while structural integrity was supported by X-ray diffraction and FTIR analyses. These study highlight the potential of Hsp-GO as a promising anti-cancer nano-drug for colon cancer therapy.

Effects of Poor Sanitation and Public Awareness in Modeling Bacterial Infection amongst the Students of a Tertiary Institution in Kaura Namoda, Zamfara State, Nigeria

Acute bacterial infection of the intestine is caused by ingestion of food or water containing vibrio cholera. The symptoms include acute water diarrhea and vomiting which can result in severe dehydration or water loss. Sanitary conditions in the environment play an important role. Hence, the objective of this paper as to evaluate the effects of poor sanitation and public awareness in modeling bacterial infection amongst the students of a tertiary institution in Kaura Namoda, Zamfara State, Nigeria. We incorporated effectiveness of drug and awareness for proper hygiene and sanitation into our model. The disease free and endemic equilibrium were determined. The effective reproduction number was showed. Numerical results of the dynamics system of the transmission of bacterial infection were presented and we found that as the effective contact rate increases, the effective reproduction number increases. Also as the effectiveness of compliance of good hygiene increases, the effective reproduction number decreases by varying the contact rate. More so, as production rate of acute diarrhea bacteria increases, it increases the secondary cases of the infected individuals.

Use of a pH-responsive imatinib mesylate sustained-release hydrogel for the treatment of tendon adhesion by inhibiting PDGFRβ/CLDN1 pathway

Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRβ/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.

Predictive and Prognostic Relevance of Tumor-Infiltrating Immune Cells: Tailoring Personalized Treatments against Different Cancer Types.

TIICs are critical components of the TME and are used to estimate prognostic and treatment responses in many malignancies. TIICs in the tumor microenvironment are assessed and quantified by categorizing immune cells into three subtypes: CD66b+ tumor-associated neutrophils (TANs), FoxP3+ regulatory T cells (Tregs), and CD163+ tumor-associated macrophages (TAMs). In addition, many cancers have tumor-infiltrating M1 and M2 macrophages, neutrophils (Neu), CD4+ T cells (T-helper), CD8+ T cells (T-cytotoxic), eosinophils, and mast cells. A variety of clinical treatments have linked tumor immune cell infiltration (ICI) to immunotherapy receptivity and prognosis. To improve the therapeutic effectiveness of immune-modulating drugs in a wider cancer patient population, immune cells and their interactions in the TME must be better understood. This study examines the clinicopathological effects of TIICs in overcoming tumor-mediated immunosuppression to boost antitumor immune responses and improve cancer prognosis. We successfully analyzed the predictive and prognostic usefulness of TIICs alongside TMB and ICI scores to identify cancer's varied immune landscapes. Traditionally, immune cell infiltration was quantified using flow cytometry, immunohistochemistry, gene set enrichment analysis (GSEA), CIBERSORT, ESTIMATE, and other platforms that use integrated immune gene sets from previously published studies. We have also thoroughly examined traditional limitations and newly created unsupervised clustering and deconvolution techniques (SpatialVizScore and ProTICS). These methods predict patient outcomes and treatment responses better. These models may also identify individuals who may benefit more from adjuvant or neoadjuvant treatment. Overall, we think that the significant contribution of TIICs in cancer will greatly benefit postoperative follow-up, therapy, interventions, and informed choices on customized cancer medicines.

Computer-Aided Drug Design (CADD): Pinostrobin and Chitosan Combination as an Antimicrobial Agent

Antimicrobial resistance causes a decrease in the effectiveness of drugs for infection therapy. CAAD can be a solution to predict solubility through chemical reactivity and interaction visibility type for new antimicrobial agents utilizing computers. The purpose of the research project was to estimate the combination of pinostrobin and chitosan's solubility and antibacterial activity. ChemBio Draw software was used to determine chemical reactivity. The solubility prediction was computed by the AutoDock Tool software. The antimicrobial activity was measured by the MOE software. Pyruvate kinase (PDB ID: 3T07), MRSA PBP2a (PDB ID: 4DKI), UPPS (PDB ID: 4H8E), and DHFR (PDB ID: 2W9S) were chosen as target proteins in the study. Pinostrobin had I, A, χ, δ, and ω values higher than those of chitosan, except ΔE, η, and μ. The interaction visibility type and bond distance between pinostrobin and chitosan, such as two conventional hydrogens (2.16-2.23 Å) and three hydrophobic pi-sigma (3.10-3.91 Å). The free energy binding value of pinostrobin, which interacted with proteins including 3T07, 4DKI, 4H8E, and 2W9S, respectively, was -6.0109, -5.4356, -6.4202, and -6.5748 kcal/mol. Chitosan with the same proteins had -11.4987, -111.1761, -11.1157, and -11.0369 kcal/mol. Pinostrobin is more stable and has lower reactivity than chitosan. The process of pinostrobin and chitosan solubility in each other was significantly impacted by the hydrogen and hydrophobic pi-sigma bonds. The antimicrobial prediction of chitosan was higher than that of pinostrobin against all target proteins. This research was the basis for isolating pinostrobin and developing a drug delivery system combined with chitosan.

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

In the United States, costs of antidiabetes medications exceed $327 billion. To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. American College of Physicians. (PROSPERO: CRD42022382315).

In vitro and in silico investigation of FDA-approved drugs to be repurposed against Alzheimer's disease.

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous systemaction for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD.

Survey on the Use of Medicines in Patients with Co-existing Hypertension and Type 2 Diabetes at the Internal Medicine Department of E Hospital in 2020-2022

The study aims to describe the situation of using antihypertensive and hypoglycemic drugs; Initial evaluation of the effectiveness of drug used in the treatment regimen of patients with concomitant hypertension and type 2 diabetes. Methods: a cross-sectional, retrospective study was performed on 179 medical records of patients who had hypertension and type 2 diabetes, examination and treatment at the Internal Medicine Department - Hospital E from April 2020 to December 2022. Information collected from medical records was processed using SPSS 26.0 statistical software. Result: the main groups of hypoglycemic drugs used were metformin (74.9%) and insulin (69,3%). The rate of using multi-drug regimen for diabetes (64.8%) is higher than that of monotherapy, in which the two-drug regimen of insulin and biguanide (metformin) is common (32.4%). The main groups of antihypertensive drugs used were ACE inhibitors and Ca channel blockers (72.6% and 57.5%), 60.3% of patients were treated according to a multi-drug regimen in which combination regimens of 2 groups of Ca channel blockers and ACE inhibitors are common (26.3%). There are no clinically significant interactions between antidiabetic and antihypertensive drugs. The rate of patients who reached the target blood pressure was 83.8%. The rate of patients achieving target blood sugar levels when discharged from the hospital was 40.9%. Conclusion: multi-drug regimen is used more than monotherapy in the treatment of hypertension and diabetes. Most patients reached target blood pressure on discharge, however the number of patients achieving target blood glucose was quite limited . No drug interactions were found between drugs used to lower blood pressure and hypoglycemic drugs.&#x0D;

Multifunctional organohydrogels for on-demand controlled drug release

Controlled drug release has sparked much attention in the field of drug delivery by prolonging the duration of drug effectiveness and reducing drug toxicity. However, the development of controlled-release drug delivery systems remains a significant challenge, primarily due to inadequate drug compatibility, low biocompatibility, and low response sensitivity of the drug carriers. Herein, an innovative strategy for fabricating multifunctional organohydrogels as drug carrier systems is designed. 1-Tetradecanol/water emulsions, stabilized by cellulose acetoacetate (CAA), are initially prepared. The organohydrogels are fabricated by the ternary enzyme-mediated polymerization of the monomer- containing emulsion. The amphipathy of CAA ensures the stability of emulsions during polymerization, and CAA participates in polymerization as an initiator. Through the reversible crystallization-melting transition of 1-tetradecanol, the drug can be encapsulated in/released from the organohydrogel. Moreover, 1-tetradecanol enhances the bioavailability of water-insoluble drugs without any additional cosolvent. Therefore, biofriendly organohydrogels can serve as ideal dressings with adjustable mechanical properties, effective temperature regulation, and temperature-triggered drug release ability.

Drug Survival, Effectiveness and Safety of Secukinumab in Axial Spondyloarthritis up to 4 Years: A Real-Life Single Center Experience.

(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2) Methods: We underwent a retrospective analysis of consecutive axSpA treated with secukinumab as a first line of biologics or at switch in a biologic-experienced population. Efficacy data, indicating improvement in inflammation parameters (such as C-reactive protein and erythrocyte sedimentation rate) and disease activity scores (such as Ankylosing Spondylitis Disease Activity Score [ASDAS-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and patient-reported outcomes (pain), were assessed at 6, 12, 24, 36 and 48 months. The drug survival rate, dropout rate and discontinuation reasons (efficacy versus safety) of secukinumab were assessed in subgroup analysis (axSpA with and without exposure to biologics). (3) Results: In total, 46 patients were exposed to the IL-17A inhibitor secukinumab. The drug survival for axSpA patients 59.7% at 12 months and 31.3% at 24 months. There were no statistically significant differences in the median drug survival between biologic-naïve versus biologic-experienced subgroups. (4) Conclusions: Secukinumab has demonstrated effectiveness and safety in treating a cohort of axSpA patients in real-world settings, with a notable retention rate of the drug.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Precision Medicine in Rheumatic Diseases: Unlocking the Potential of Antibody-Drug Conjugates.

In the era of precision medicine, antibody-drug conjugates (ADCs) have emerged as a cutting-edge therapeutic strategy. These innovative compounds combine the precision of monoclonal antibodies with the potent cell-killing or immune-modulating abilities of attached drug payloads. This unique strategy not only reduces off-target toxicity but also enhances the therapeutic effectiveness of drugs. Beyond their well established role in oncology, ADCs are now showing promising potential in addressing the unmet needs in the therapeutics of rheumatic diseases. Rheumatic diseases, a diverse group of chronic autoimmune diseases with varying etiologies, clinical presentations, and prognoses, often demand prolonged pharmacological interventions, creating a pressing need for novel, efficient, and low-risk treatment options. ADCs, with their ability to precisely target the immune components, have emerged as a novel therapeutic strategy in this context. This review will provide an overview of the core components and mechanisms behind ADCs, a summary of the latest clinical trials of ADCs for the treatment of rheumatic diseases, and a discussion of the challenges and future prospects faced by the development of next-generation ADCs. SIGNIFICANCE STATEMENT: There is a lack of efficient and low-risk targeted therapeutics for rheumatic diseases. Antibody-drug conjugates, a class of cutting-edge therapeutic drugs, have emerged as a promising targeted therapeutic strategy for rheumatic disease. Although there is limited literature summarizing the progress of antibody-drug conjugates in the field of rheumatic disease, updating the advancements in this area provides novel insights into the development of novel antirheumatic drugs.

Genetic diversity of cytochrome P450 in patients receiving psychiatric care in Greece: a step towards clinical implementation.

Aim: We herein inferred the genetic diversity of CYP450 isoenzymes to predict the percentage of patients who need dose adjustment in drugs used in psychiatry.Materials & methods: Data of 784 Greek patients receiving psychiatric care who were genotyped for CYP2D6, CYP2C19, CYP1A2, CYP3A5 and CYP2C9 isoenzymes were inferred to gene-drug pairs according to the US FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group annotations and published literature.Results: Atypical metabolism was found for 36.8% of patients in CYP2D6, 49.2% in CYP2C19, 45% in CYP1A2, 16.7% in CYP3A5 and 41.8% in CYP2C9. Dosage adjustment need was estimated for 10.2% of venlafaxine, 10.0% of paroxetine, 6.4% of sertraline, 30.8% of citalopram, 52.1% of escitalopram, 18.2% of fluvoxamine, 54.1% of tricyclic antidepressants, 16.7% of zuclopenthixol, 10.6% of haloperidoland 13.3% of risperidone treated patients.Conclusion: Clinical psychiatric pharmacogenomic implementation holds promise to improve drug effectiveness and safety.

Clinical observation of the long-term course of COVID-19 infection in a patient with an immunodeficiency condition

The new coronavirus infection caused by the SARS-CoV-2 virus has become a real challenge for the world’s population. Despite the fact that vaccines have been developed and the effectiveness of antiviral drugs has been demonstrated, COVID-19 continues to be an urgent problem. SARS-CoV-2 is genetically modified due to the accumulation of mutations, new strains with high virulence appear that distort the immune response. In addition, it has been shown that the virus can persist in the body for a long time, which ensures the maintenance of an inflammatory response and causes the persistence and recurrence of symptoms after acute infection, especially in certain groups of patients. The article presents a clinical case of a long-term course of new coronavirus infection with predominant lung damage in the form of interstitial changes and persistent inflammation for 7 months from the moment of diagnosis against the background of an immunodeficiency condition due to the patient’s lymphoma in remission after polychemotherapy, exclusion of pulmonary embolism and progression of lymphoproliferative disease. The article highlights the difficulties of determining the criteria for a post-COVID and the features of its treatment using long-term therapy with systemic glucocorticosteroids, inhalation administration of tauractant (Surfactant-BL) in comparison with the dynamic assessment of total ventilation disorders and dynamic control of MSCT of the chest organs. Thus, the importance of identifying risk factors for the progression of COVID-19-associated conditions in patients with different comorbid backgrounds and identifying criteria for the development of new long-COVID treatment strategies is emphasized.

Drawing attention to previous studies can reduce confidence in a new research finding, even when confidence should increase.

People often learn of new scientific findings from brief news reports, and may discount or ignore prior research, potentially contributing to misunderstanding of findings. In this preregistered study, we investigated how people interpret a brief news report on a new drug for weight loss. Participants read an article that either highlighted the importance of prior research when judging the drug's effectiveness, or made no mention of this issue. For articles describing no prior research, mean confidence in the drug was 62%. For articles that noted prior research was conducted, confidence increased as the proportion of studies with positive findings increased. When prior research was highlighted, confidence decreased by a small amount, even when it should have increased (i.e., even when most of the evidence supported the drug's effectiveness). Thus, people's judgements were more sceptical, but not necessarily more accurate. Judgements were not affected by education level, statistics experience, or personal relevance of the research topic.

Abstract LB258: ZDHHC20 is a potential target for overcoming ABCB1-mediated multidrug resisance (MDR) in cancer

Abstract ABCB1-mediated multidrug resistance (MDR) in cancer cells is an increasingly important cause of anticancer drug treatment failure. The occurrence of MDR in cancer reduces the effectiveness of antitumor drugs, which results in poor quality of life and increased mortality of patients, and creates a heavy burden for the patient's family and society. Hence, the reversal of ABCB1-mediated MDR in cancer is a highly urgent clinical need. Although reversal agents targeting ABCB1 have been developed and partially tested in clinical trials, their main mechanism limits to inhibit the function of ABCB1 efflux pumps, which lacks tumor tissue specificity and has poor clinical effects, and the development of ABCB1-based resistance reversal strategies has entered a bottleneck. ABCB1 mediates tumor MDR through drug efflux and lysosomal segregation, and intervention in the plasma membrane/lysosomal membrane localization of ABCB1 is a potential strategy to reverse drug resistance. Palmitoylation, as a post-translational lipid modification, plays an important role in protein anchoring, transport, and functional regulation, and is highly relevant to human tumors. In the present study, palmitoylation modification was first identified as a key post-translational lipid modification of ABCB1. ABCB1 is palmitoylated in its cytoplasmic domain, which is further stabilized by blocking its ubiquitination, consequently suppressing ABCB1 degradation by lysosomes. We identified palmitoyltransferase ZDHHC20 (DHHC20) as the main acetyltransferase required for the palmitoylation of ABCB1, and show that the inhibition of ABCB1 palmitoylation via 2-bromopalmitate (2-BP), or the silencing of DHHC20, decreases ABCB1 expression and overcomes MDR in vitro as well as in mice bearing SW620/Ad300 resistance cells. Moreover, Cysteine residues C787 was identified as the main palmitoylation cite in human ABCB1. Database and RNAseq analyses revealed that ZDHHC20 is highly expressed in tumor tissues and tumor MDR cells, which makes it a potential tumor tissue-specific target for overcoming ABCB1-mediated MDR in cancer. Our results firstly identified the novel post-translational modification (palmitoylation) of ABCB1 and provide a new research direction and theoretical basis for breaking through the bottleneck of the development of reversal agents for ABCB1-mediated MDR in cancer. Citation Format: Ning Ji, Xin Peng, Yi-nan Liu, Yuqi Yang, Zhe-Sheng Chen, Dexin Kong, Yueguo Li. ZDHHC20 is a potential target for overcoming ABCB1-mediated multidrug resisance (MDR) in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB258.

Emerging In Vitro and In Vivo Models: Hope for the Better Understanding of Cancer Progression and Treatment.

Various cancer models have been developed to aid the understanding of the underlying mechanisms of tumor development and evaluate the effectiveness of various anticancer drugs in preclinical studies. These models accurately reproduce the critical stages of tumor initiation and development to mimic the tumor microenvironment better. Using these models for target validation, tumor response evaluation, resistance modeling, and toxicity comprehension can significantly enhance the drug development process. Herein, various in vivo or animal models are presented, typically consisting of several mice and in vitro models ranging in complexity from transwell models to spheroids and CRISPR-Cas9 technologies. While in vitro models have been used for decades and dominate the early stages of drug development, they are still limited primary to simplistic tests based on testing on a single cell type cultivated in Petri dishes. Recent advancements in developing new cancer therapies necessitate the generation of complicated animal models that accurately mimic the tumor's complexity and microenvironment. Mice make effective tumor models as they are affordable, have a short reproductive cycle, exhibit rapid tumor growth, and are simple to manipulate genetically. Human cancer mouse models are crucial to understanding the neoplastic process and basic and clinical research improvements. The following review summarizes different in vitro and in vivo metastasis models, their advantages and disadvantages, and their ability to serve as a model for cancer research.