Drug Application Research Articles

Practical considerations in the establishment of psychedelic research programs.

There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs. This article provides recommendations that may be helpful to investigators seeking to work with psychedelics, with a focus on academic medical centers in the United States. The academic literature on relevant matters is reviewed, and the authors provide observations from their experiences either working for relevant regulatory agencies or conducting basic science studies, investigator-initiated trials, or industry sponsored trials with psychedelics. Investigators planning to conduct psychedelic research should cultivate broad institutional support early. Challenges related to securing funding, obtaining approval for an Investigational New Drug application from the Food and Drug Administration, clinical grade drug sourcing, obtaining a Schedule I researcher registration from the Drug Enforcement Administration and an equivalent state license (if required), preparing spaces for treatment and study drug storage, managing controlled substance inventory, engaging the local community, and other issues should be anticipated. Investigators should anticipate several implementation challenges when planning to work with psychedelics. However, these are likely surmountable with planning, persistence, and assistance from colleagues and other experts.

Autodegradable Polymers: Complete Degradation without Any Trigger, Tunable Performance, and Biomedical Applications.

Degradable polymers are an emerging research interest. The innovation of new degradable polymers for biomedical applications is challenging due to strict demands including nontoxicity of polymers and degraded products, complete degradation to avoid polymer residues in the body, and other suitable properties. Here, we demonstrate a series of degradable polymers for sustained-release drug applications synthesized by the alternating copolymerization of cyclic anhydrides and Schiff bases. In addition to common feedstocks, the copolymerization is versatile and catalyst-free, affording polymers incorporating cyclic topologies and in-chain ester and peptoid groups. Particularly, the polymers exhibit self- and autodegradation without any trigger, which is distinct from remaining degradation mechanisms. The degradation performance is widely regulated by the polymer structure and external temperature, resulting in complete degradation from a few hours to several months. Owing to their unique properties, the polymers are approved for biomedical applications, as revealed soundly through cell viability assay, in vitro and in vivo drug release.

Comprehensive applications of the artificial intelligence technology in new drug research and development.

Target-based strategy is a prevalent means of drug research and development (R&D), since targets provide effector molecules of drug action and offer the foundation of pharmacological investigation. Recently, the artificial intelligence (AI) technology has been utilized in various stages of drug R&D, where AI-assisted experimental methods show higher efficiency than sole experimental ones. It is a critical need to give a comprehensive review of AI applications in drug R &D for biopharmaceutical field. Relevant literatures about AI-assisted drug R&D were collected from the public databases (Including Google Scholar, Web of Science, PubMed, IEEE Xplore Digital Library, Springer, and ScienceDirect) through a keyword searching strategy with the following terms [("Artificial Intelligence" OR "Knowledge Graph" OR "Machine Learning") AND ("Drug Target Identification" OR "New Drug Development")]. In this review, we first introduced common strategies and novel trends of drug R&D, followed by characteristic description of AI algorithms widely used in drug R&D. Subsequently, we depicted detailed applications of AI algorithms in target identification, lead compound identification and optimization, drug repurposing, and drug analytical platform construction. Finally, we discussed the challenges and prospects of AI-assisted methods for drug discovery. Collectively, this review provides comprehensive overview of AI applications in drug R&D and presents future perspectives for biopharmaceutical field, which may promote the development of drug industry.

Current Regulations of Herbal Medicines in the US and EU

Background: If a herbal pharmaceutical is intended to impact the function of the human organism, it is categorized as a medication or a nutritional supplement. According to the FDA, the medicine must be offered under a New Drug Application (NDA). The European Medicine Agency (EMA) has established two methods for registering herbal medicals: Under Directive 2001/83/EC, a full marketing authorization (MA) is obtained by submitting a dossier containing data about the quality, safeness, and effectiveness of pharmaceuticals, which include physical and chemical, biological, or microbiological tests, as well as pharmacological, toxicological, and clinical trial documentation; There is a simplest technique under Directive 2004/24/EC for classical herbals that do not needs professional monitoring and where the indication of long history use of pharmaceuticals exists and appropriate relevant journals to illustrate a very well medicinal usage is not provided. Aim: A study about the regulatory status of herbal drugs/products was conducted in America and Europe to understand the various classes under which the sale of herbal goods is authorized and their premarketing criteria. Materials and Methods: This study has been performed by gathering information from the official websites of the USFDA and EMA. Results: A thorough evaluation was carried out in order to identify the impediments to the harmonization of herbal goods. Conclusion: Aside from the challenges of herb supply and conservation, it has been shown that there is a lack of uniformity in the regulatory standards of herbal supplements globally. These are impeding international commerce and the expansion of the herbal goods market. USFDA classifies botanical items as pharmaceutical, nutrition, or dietary supplement based on the indications or ultimate use.

Liver Metabolism Insights into the Anti-Hyperuricemia Effects of Polygonum cuspidatum in Mice

At present, hyperuricemia (China) has shown a trend of high incidence and younger age, which has attracted widespread attention. Polygonum cuspidatum extracts are thought to have a role in regulating HUA (Hyperuricemia). Here, we use a combination of GC-TOF/MS-based and UPLC-MSMS-based metabolomic and lipidomic techniques, it was revealed that a Polygonum cuspidatum extract (1-(4-hydroxy-2-methoxy phenyl) -2-(4-hydroxy-3,5-dimethylphenyl) butane-1,2,3-triol) regulates the effect of HUA by altering the liver metabolism of HUA mice. The research results indicate that the anti-HUA activity of P. cuspidatum is closely related to pathways such as sugar metabolism, amino acid metabolism, and purine and pyrimidine metabolism. Participating in metabolic activities exerts antioxidant effects and alleviates UA (Uric acid) accumulation. Additionally, liver lipidomics studies have shown that the overall content of four major phospholipids (Phosphatidyl glycerol, Lysophosphatidyl glycerol, Phosphatidyl cholines, and phosphatidylcholine) and sphingomyelin lipids in sphingolipids are significantly upregulated, while the overall level of CER (Ceramide) lipids is reduced. This indicates that the anti-HUA effect of the components of P. cuspidatum is mainly related to improving glycerophospholipid metabolism and regulating the SM(sphingomyelin)-CER pathway, thereby reducing inflammation and abnormal liver metabolism, and further maintaining uric acid homeostasis. This study provides an in-depth mechanism analysis for the potential application of P. cuspidatum in the treatment of HUA, laying a foundation for the development and clinical application of related drugs.

The future of medicine: Strategic insights into drug repurposing

The future of medicine is increasingly being shaped by innovative strategies that maximize the efficacy of existing therapeutics, one of the most promising being drug repurposing. Drug repurposing involves the identification of novel therapeutic applications for approved or investigational drugs, thereby circumventing the lengthy and costly processes associated with traditional drug development. This approach not only accelerates the delivery of treatments to patients but also optimizes existing resources, making it a compelling strategy in the face of rising healthcare costs and the urgent need for novel therapies. Recent advancements in genomics, bioinformatics, and high-throughput screening have revolutionized our ability to identify potential candidates for repurposing. These technologies facilitate the exploration of drug-target interactions across various diseases, enabling researchers to uncover unexpected therapeutic potentials. For instance, well-known medications originally developed for one condition have been found effective in treating others, such as the use of thalidomide for multiple myeloma and the repurposing of antifungal agents for cancer therapy.

Neurochemical characterization of 5-HT2AR partial agonists with simultaneous PET-MRI.

Understanding neuromodulatory effects of serotonin 2A receptor (5-HT2AR) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine partial agonists with varying 5-HT2AR affinities and selectivity profiles: psilocybin (30, 60, and 90 µg/kg), lisuride (5 µg/kg), and 25CN-NBOH (15 µg/kg). Receptor occupancy was assessed with [11C]MDL-100907 PET, and cerebral blood volume (CBV) changes were measured with phMRI. Mixed partial agonists psilocybin and lisuride evoked biphasic CBV responses, whereas the selective 25CN-NBOH produced monophasic CBV increases. Cortical occupancy for psilocybin plateaued at 60 µg/kg (32%), whereas a lower dose of lisuride (5 µg/kg) resulted in similar occupancy (31%). Administration of 25CN-NBOH resulted in lower occupancy (7%) but larger changes in CBV compared to psilocybin and lisuride. The associations between CBV and 5-HT2AR occupancy appear linear for lisuride and 25CN-NBOH, but not for psilocybin. We speculate that the temporal and spatial differences in hemodynamic responses of the three agonists could stem from mixed affinity profiles. This work provides an understanding of pharmacological impacts of mixed serotonergic agonists being pursued as therapeutics for psychiatric conditions, offering valuable insights for future drug applications and development strategies.

Recommendation for Clarifying FDA Policy in Evaluating "Sameness" of Higher Order Structure for Generic Peptide Therapeutics.

Recognizing the approach of a dramatic expansion of peptide therapeutics reaching the marketplace in recent years, led by GLP-1 receptor agonists such as semaglutide and liraglutide, the Center for Drug Evaluation and Research (CDER) branch of the US Food and Drug Administration (FDA) issued a final guidance in 2021 that was intended to assist generic drug producers in meeting Abbreviated New Drug Application (ANDA) obligations to establish "sameness" of their active peptide drug relative to that produced by innovator companies. Research and a published report by FDA scientists on best practices followed, which promulgated the use of nuclear magnetic resonance (NMR) and principal component analysis (PCA) and established a quantitative standard by which "sameness" of higher order structure for the applicant's peptide drug could be judged. A key requirement is that drug product samples be analyzed directly and non-invasively, a condition which in practice restricts sample modification to the addition of a small amount of deuterium oxide to allow signal lock and spectral data alignment (as required for NMR analysis). In the study described herein, data are presented to illustrate that 1) relatively small differences in sample pH can cause significant shifting of certain proton resonances, 2) that such resonance shifting is readily reversible and due to the degree of protonation of specific amino acid residues (rather than reflecting differences in higher order structure), and 3) that small differences in pH variability between sample cohorts can frequently cause failure to meet the quantitative benchmark established by the agency. Methodology is presented by which drug sample pHs can be aligned with minimal impact, and a recommendation is made that minor sample pH adjustments be allowed in assessing "sameness" of peptide drug higher order structure.

Assessing the impact of three fish drugs on tetrahymenosis in Fish using environmental DNA techniques

Tetrahymenosis has resulted in significant economic losses for the ornamental fish farming industry in Harbin. While previous studies have investigated the outbreaks and histopathology of Tetrahymena pyriformis in fish, there is still a lack of study on the use of the application of fish drugs for prevention and treatment. This experiment aims to evaluate the efficacy of three fish drugs (copper, Nitrofural, Methylene Blue) in combating tetrahymenosis in goldfish. We utilized eDNA-based 16 s rDNA gene amplifiers sequencing and qPCR technologies to extract environmental samples and conducted high-throughput sequencing to assess the interaction between the diversity of T. pyriformis and other microorganisms in aquaculture water following the introduction of various fish medications. Our findings revealed that among the three fish drugs test, Nitrofural displayed the most promising effects, followed by Methylene Blue, while copper sulfate proved to be the least effective. Consequently, our study provides a treatment plan for addressing tetrahymenosis in goldfish and offers insights into the pathological changes in goldfish tissues following the onset of the disease.

Praeruptorin A screened by a ferrous ion probe inhibited DMT1 and ferroptosis to attenuate Doxorubicin-induced cardiomyopathy

Doxorubicin (DOX)-induced cardiomyopathy (DIC) greatly limits its clinical application of the anticancer drug. Therefore, there is an immediate necessity to undertake intervention studies to minimize DIC, encompassing the screening of regulatory compounds and delving into the underlying regulatory mechanisms. A growing body of research suggests that ferroptosis is an essential process in the development of DIC. Here, we demonstrated that DOX causes elevated iron levels in cardiomyocytes and mouse hearts, and leads to ferroptosis and cardiac insufficiency. Next, we performed high-throughput screening of a library of herbal small molecule compounds for novel compounds that inhibit ferroptosis, using Fe2+ levels as a screening index for DIC prevention and treatment drugs. We found that Praeruptorin A (PA) was able to reduce Fe2+ concentration in cardiomyocytes, inhibit ferroptosis, and alleviate DIC and cardiac dysfunction in mice. Concurrently, PA exhibits a synergistic effect with DOX in suppressing the proliferation of carcinoma of breast MCF-7 cell in nude mice. Mechanistically, we found that PA inhibited the expression of divalent metal transporter protein 1 (DMT1), suppressed Fe2+ overload in cardiomyocytes, and inhibited ferroptosis, thereby alleviating DIC. Our study demonstrated the feasibility of high-throughput screening targeting the Fe2+ concentration, and elucidated the role and mechanism of PA in alleviating DIC, which provides a new possibility.

TPepPro: a deep learning model for predicting peptide-protein interactions.

Peptides and their derivatives hold potential as therapeutic agents. The rising interest in developing peptide drugs is evidenced by increasing approval rates by the FDA of USA. To identify the most potential peptides, study on peptide-protein interactions presents a very important approach but poses considerable technical challenges. In experimental aspects, the transient nature of peptide-protein interactions (PepPIs) and the high flexibility of peptides contribute to elevated costs and inefficiency. Traditional docking and molecular dynamics simulation methods require substantial computational resources, and the predictive accuracy of their results remain unsatisfactory. To address this gap, we proposed TPepPro, a Transformer-based model for PepPI prediction. We trained TPepPro on a dataset of 19,187 pairs of peptide-protein complexes with both sequential and structural features. TPepPro utilizes a strategy that combines local protein sequence feature extraction with global protein structure feature extraction. Moreover, TPepPro optimizes the architecture of structural featuring neural network in BN-ReLU arrangement, which notably reduced the amount of computing resources required for peptide-protein interactions prediction. According to comparison analysis, the accuracy reached 0.855 in TPepPro, achieving an 8.1% improvement compared to the second-best model TAGPPI. TPepPro achieved an AUC of 0.922, surpassing the second-best model TAGPPI with 0.844. Moreover, the newly developed TPepPro identify certain PepPIs that can be validated according to previous experimental evidence, thus indicating the efficiency of TPepPro to detect high potential PepPIs that would be helpful for amino acid drug applications. The source code of TPepPro is available at https://github.com/wanglabhku/TPepPro. Supplementary data are available at Bioinformatics online.\.

Research status, hotspots, and implications of seasonal affective disorder: A bibliometric analysis based on CiteSpace and VOSviewer

The objective was to determine the research status and hotspots of seasonal affective disorders (SAD) based on bibliometric tools, which will contribute to the further research in this field. We used bibliometric tools CiteSpace and VOSviewer to conduct visual quantitative analysis on 465 SAD literatures in the Web of Science core database from 2008 to 2023 from multiple perspectives such as collaboration network, keywords, and literature citations. At the same time, we used Microsoft Word to make relevant tables. The publication of SAD-related literature has been on the rise in the past 15 years, countries with high production of SAD literature are mainly concentrated in the United States, Austria, and Canada, and certain cooperative relationships have been established between various institutions and scholars. Research keywords in our study are mainly limited to pathogenesis (“Photoperiod,” “exposure,” “winter,” “serotonin transporter,” and “creb”) and treatment measures (“light therapy” and “melatonin”). In recent years, literature research hotspots mainly focus on the treatment of SAD with light therapy, the application of exogenous drugs, the biological clock mechanism of SAD pathogenesis, the relationship between SAD and inflammation, etc. The correlation between SAD and sleepiness and alternative treatments to light therapy may be future research hotspots. The research results reveal the future research focus of SAD. There is a considerable interest in the photoperiodic pathogenesis of SAD, light therapy and its alternative therapies, and there is still hope for further exploration. Substantial research into evidence-based prevention as well as treatment strategies is necessary to improve outcomes.

Allylation of Lactol in Water.

We developed a water-promoted cross-coupling of 3-hydroxyisobenzofuran-1(3H)-ones and allylic boronates under biocompatible conditions. This approach facilitates the synthesis of diverse 3-allylic phthalides with high yields and exceptional selectivity in a metal-free manner. The versatility and practicality of this protocol underscore its significant potential for drug development and applications in medicinal chemistry.

Evaluation of physical and chemical modifications to drug reservoirs for stimuli-responsive microneedles.

Hydrogel-forming microneedle (MN) arrays are minimally-invasive devices that can penetrate the stratum corneum, the main barrier to topical drug application, without causing pain. However, drug delivery using hydrogel-forming MN arrays tends to be relatively slow compared to rapid drug delivery using conventional needles and syringes. Therefore, in this work, for the first time, different physical and chemical delivery enhancement methods were employed in combination with PVA-based hydrogel-forming MN arrays. Using a model drug, ibuprofen (IBU) sodium, the designed systems were assessed in terms of the extent of transdermal delivery. Iontophoresis (ITP) and heat-assisted drug delivery technology were investigated as physical permeation enhancement techniques. Ex vivo studies demonstrated that the ITP (0.5mA/cm2)-mediated combination strategy significantly enhanced the transdermal permeation of IBU sodium over the first 6h (~ 5.11mg) when compared to MN alone (~ 1.63mg) (p < 0.05). In contrast, heat-assisted technology showed almost no promoting effect on transdermal delivery. Furthermore, IBU sodium-containing rapidly dissolving lyophilised and effervescent reservoirs, classified as chemical modification methods, were prepared. Both strategies achieved rapid and effective ex vivo IBU sodium permeation, equating to ~ 78% (30.66mg) and ~ 71% (28.43mg) from lyophilised and effervescent reservoirs, respectively. Moreover, in vivo pharmacokinetic studies showed that the IBU sodium plasma concentration within lyophilised and effervescent groups reached a maximum concentration (Cmax) at 4h (~ 282.15µg/mL) and 6h (~ 140.81µg/mL), respectively. These strategies not only provided rapid achievement of therapeutic levels (10-15µg/ml), but also resulted in sustained release of IBU sodium for at least 48h, which could effectively reduce the frequency of administration, thereby improving patient compliance and reducing side effects of IBU sodium.

Harnessing the power of social media: transforming nursing education for unmatched academic success.

This study aimed to determine the effect of social media-supported learning on the academic achievement of nursing students and their social media usage levels in nursing education. Using social media in nursing education enables students to experience interactive learning, strengthening learning outcomes and creating an enriched learning environment with up-to-date information. The study was conducted as a randomized controlled study. CONSORTchecklist was completed. The subject of parenteral drug administration was explained interactively to all students by the same instructors for a total of 12h for weeks. After the theoretical course, each skill was demonstrated by the instructor in the laboratory setting in a 24-h laboratory course with the demonstration method in line with the checklists. After the training was completed, the students filled out the necessary forms. Videos and informative images about parenteral drug applications were shared with the intervention group for 4weeks through an Instagram page created for social media-supported learning. Questions and answers were shared on the subject every day in the story section. The answer to the question was shared in the story section the next day with explanations. At the end of the 4th training week, the students were asked to complete the necessary forms as a post-test. Changes in academic achievement and social media usage after the intervention were measured using achievement tests and the Social Media Scale in Nursing Education. Data were analyzed with SPSS 23.0. Normality was tested using the Shapiro-Wilk test. Independent t-tests and the Chi-Square test for categorical variables were used for normally distributed continuous variables. Pre-test and post-test comparisons within groups were evaluated with the Paired t-test if normality was met, or the Wilcoxon test. The effect size was calculated using Cohen's d. After social media-supported learning, it was found that the difference between the post-test mean scores of the nursing students in the intervention and control group was statistically significant(p < 0.001). It was also found that the average of the exam results after the training increased compared to the average before the training, and the difference between the two scores was statistically significant(p < 0.001). Social media-supported education positively affected the academic achievements of nursing students and the level of social media use in nursing education.

PPARA variant rs1800234 had a dose dependent pharmacogenetics impact on the therapeutic response to chiglitazar.

Our objective was to explore the pharmacogenetic impact of three known functional variants in drug target genes and determine whether they can explain the inter-individual variation in therapeutic response. In a post hoc analysis of data from randomized controlled clinical trials of chiglitazar, we genotyped 481 Chinese patients with T2DM and investigated the association of variants in PPAR genes with the therapeutic outcome separated by dose using linear regression. rs1800234, a gain-of-function variant of PPARA, had a dose-dependent pharmacogenetic impact on the therapeutic response to chiglitazar. The C allele was significantly associated with reduced therapeutic response in the 48 mg group, while no significant association was observed in the 32 mg group. In addition, in patients without the C allele, patients treated with 48 mg chiglitazar had a better therapeutic response than those treated with 32 mg chiglitazar. To the contrary, in patients with the C allele, patients treated with 48 mg chiglitazar had a worse therapeutic response than those treated with 32 mg of chiglitazar. The PPARA variant rs1800234had a dose-dependent pharmacogenetic impact on the therapeutic response to chiglitazar. It could help explain the absence of a dose effect of chiglitazar and serve as a potential biomarker for the chosen dose of chiglitazar in the future. In addition, our study provided important reference for the design and clinical application of multi-target drugs.

Dose-related effect of acetylcholine on human gingival blood flow

BackgroundThis study investigates the dose-response relationship of acetylcholine (ACh) on healthy human gingival blood flow (GBF). Understanding this dose-response relationship contributes to studying vasodilatory mechanisms in various pathological conditions.MethodsThe study involved 22 young healthy men (21 - 32 years) to investigate the dose-response relationship of ACh on GBF. Semi-circular wells were created on the labial surface of the upper right second incisor (FDI #12) and upper left first incisor (FDI #21), including the gingival sulcus, for the application of drugs. ACh-chloride solutions at 0.1, 1, and 10 mg/mL were administered to the gingival sulcus of tooth FDI #12 with a Hamilton syringe. Physiological saline was applied on the contralateral side to FDI #21 as a control. The GBF was measured non-invasively by the laser speckle contrast imaging method in four 1mm high adjacent regions: coronal, midway1, midway2, and apical, and was expressed in a laser speckle perfusion unit (LSPU). After the baseline blood flow recording, ACh doses were applied sequentially, with washout periods in between. Data were statistically analyzed using a linear mixed model.ResultsThe GBF did not change on the saline site throughout the experiment. The GBF was significantly higher at the coronal region after all ACh doses (baseline: 218±31 LSPU, and 227±38 LSPU p < 0.05, 239±40 LSPU p < 0.001, 291±54 LSPU p < 0.001, respectively) compared to the saline. It was also elevated following 1 and 10 mg/mL at the midway1 (245±48 LSPU,p < 0.05, 293±65 LSPU p < 0.001). At midway2 and apical, only the 10 mg/mL dose was effective (285±71 LSPU, p < 0.001; 302±82 LSPU, p < 0.001).ConclusionsOur findings suggest a dose-dependent vasodilation to ACh, emphasizing its role in human gingival microcirculation. Only the 10 mg/mL ACh could evoke remote vasodilation 3 mm from the application. The described method could facilitate the investigation of endothelium-dependent vasodilation in disorders affecting microcirculation, such as periodontitis or diabetes.

Research Progress on the Application of Natural Medicines in Biomaterial Coatings.

With the continuous progress of biomedical technology, biomaterial coatings play an important role in improving the performance of medical devices and promoting tissue repair and regeneration. The application of natural medicine to biological materials has become a hot topic due to its diverse biological activity, low toxicity, and wide range of sources. This article introduces the definition and classification of natural medicines, lists some common natural medicines, such as curcumin, allicin, chitosan, tea polyphenols, etc., and lists some biological activities of some common natural medicines, such as antibacterial, antioxidant, antitumor, and other properties. According to the different characteristics of natural medicines, physical adsorption, chemical grafting, layer-by-layer self-assembly, sol-gel and other methods are combined with biomaterials, which can be used for orthopedic implants, cardiovascular and cerebrovascular stents, wound dressings, drug delivery systems, etc., to exert their biological activity. For example, improving antibacterial properties, promoting tissue regeneration, and improving biocompatibility promote the development of medical health. Although the development of biomaterials has been greatly expanded, it still faces some major challenges, such as whether the combination between the coating and the substrate is firm, whether the drug load is released sustainably, whether the dynamic balance will be disrupted, and so on; a series of problems affects the application of natural drugs in biomaterial coatings. In view of these problems, this paper summarizes some suggestions by evaluating the literature, such as optimizing the binding method and release system; carrying out more clinical application research; carrying out multidisciplinary cooperation; broadening the application of natural medicine in biomaterial coatings; and developing safer, more effective and multi-functional natural medicine coatings through continuous research and innovation, so as to contribute to the development of the biomedical field.

PARP inhibitor drugs and their targeted therapy for BRCA gene mutations

Abstract. Poly ADP-Bibose polymerase (PARP) inhibitors have attracted wide attention as a new class of anticancer drugs. PARP inhibitors act by blocking PARP binding to sites of DNA damage, leading to failure of DNA repair and ultimately leading to apoptosis of tumor cells. In recent years, PARP inhibitors have achieved remarkable clinical results in a variety of cancer treatments, especially in BRCA mutation-associated breast and ovarian cancer treatments. The application of these PARP inhibitor drugs has significantly prolonged the survival of patients associated with BRCA mutations and improved the quality of life of patients. The limitations of PARP inhibitors are mainly manifested in two aspects: first, their specificity for PARP-1 is not high enough to lead to side effects after taking drugs; second, patients may develop resistance during long-term use of such drugs. In this paper, the mechanism of action of PARP inhibitors is reviewed, and deeply analyzed the chemical structure and efficacy of Olaparib, Niraparib and Rucaparib drugs, which provided a useful reference for subsequent clinical research and drug development.

Analysis of gastric cancer medication by exploring fluorouracil drugs

Abstract. Gastric cancer (GC), as one of the most important types of cancer with a very high incidence rate in China, is in urgent need of treatment. China has made certain progress, such as the widespread use of fluorouracil and other drugs in the treatment of gastric cancer, as well as the use of various treatment methods such as surgery and chemotherapy. This article aims to explore the efficacy of fluorouracil drugs in the treatment of gastric cancer and their combined application with other drugs. By analyzing the correlation between peripheral blood platelet levels and the efficacy of oxaliplatin combined with fluorouracil chemotherapy in gastric cancer patients, as well as the effects of two chemotherapy regimens, docetaxel combined with oxaliplatin, tigio and docetaxel combined with cisplatin and fluorouracil, on advanced gastric cancer, it was found that fluorouracil drugs, as cell cycle inhibitors, have an inhibitory effect on cell division and have a significant effect in the treatment of gastric cancer. Future research can further deepen the combined application of fluorouracil drugs with other drugs to reduce complications and improve treatment effectiveness. It is suggested that future research should focus on in-depth exploration of targeted drug delivery, combined with new biotechnology, to improve the efficiency and accuracy of gastric cancer treatment.