Drug Safety Research Articles

Current and experimental pharmacotherapy for the management of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with its incidence increasing in parallel with the global prevalence of obesity and type 2 diabetes mellitus. Despite our steadily increasing knowledge of its pathogenesis, there is as yet no available pharmacotherapy specifically tailored for NAFLD. To define the appropriate management, it is important to clarify the context in which the disease appears. In the case of concurrent metabolic comorbidities, NAFLD patients are treated by targeting these comorbidities, such as diabetes and obesity. Thus, GLP-1 analogs, PPAR, and SGLT2 inhibitors have recently become central to the treatment of NAFLD. In parallel, randomized trials are being conducted to explore new agents targeting known pathways involved in NAFLD progression. However, there is an imperative need to intensify the effort to design new, safe drugs with biopsy-proven efficacy. Of note, the main target of the pharmacotherapy should be directed to the regression of fibrotic NASH, as this histologic stage has been correlated with increased overall as well as liver-related morbidity and mortality. Herein we discuss the drugs currently at the forefront of NAFLD treatment.

In Silico Approach for Assessment of the Anti-tumor Potential of Cannabinoid Compounds by Targeting Glucose-6-phosphate Dehydrogenase Enzyme.

Glucose-6-phosphate dehydrogenase (G6PD) is a pentose phosphate pathway (PPP) enzyme that generates NADPH, which is required for cellular redox equilibrium and reductive biosynthesis. It has been demonstrated that abnormal G6PD activation promotes cancer cell proliferation and metastasis. To date, no G6PD inhibitor has passed clinical testing successfully enough to be launched as a medicine. As a result, in this investigation, cannabinoids were chosen to evaluate their anticancer potential by targeting G6PD. Molecular docking indicated that three molecules, Tetrahydrocannabinolic acid (THCA), Cannabichromenic acid (CBCA), and tetrahydrocannabivarin (THCV), have the highest binding affinities for G6PD of -8.61, - 8.39, and 8.01 Kcal/mol. ADMET analysis found that all of them were safe prospective drug candidates. Molecular dynamics (MD) simulation and MM-PBSA analysis confirm the structural compactness and lower conformational variation of protein-ligand complexes, thereby maintaining structural stability and rigidity. Thus, our in silico investigation exhibited all three cannabinoids as potential competitive inhibitors of G6PD.

An Investigation of In Vitro Anti-Cancer Efficacy of Dihydroartemisinin-Loaded Bovine Milk Exosomes Against Triple-Negative Breast Cancer.

Repurposing drugs offers several advantages, including reduced time and cost compared to developing new drugs from scratch. It leverages existing knowledge about drug safety, dosage, and pharmacokinetics, expediting the process of clinical trials and regulatory approval. Dihydroartemisinin (DHA) is a semi-synthetic and active metabolite of all artemisinin molecules and is FDA-approved for the treatment of malaria. Apart from having anti-malarial properties, DHA also possesses anticancer properties. However, its pharmacological actions are limited by toxicity and solubility problems. To overcome these challenges and enhance its anticancer effectiveness, we designed an exosomal formulation of DHA. We isolated exosomes from bovine milk using differential ultracentrifugation and loaded DHA using sonication. Scanning and transition electron microscopy revealed a size of roughly 100nm, with a spherical shape. Furthermore, in pH 7.4 and 5.5, the exosomes exhibited burst release followed by sustained release. Multiple in vitro cell culture tests demonstrated that Exo-DHA exhibited enhanced anticancer activity, including cytotoxicity, cellular uptake, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, and inhibition of colony formation. Additional evidence supporting Exo-DHA's anti-migration ability came from transwell migration and scratch assays. Based on these results, it was concluded that the anticancer efficacy of DHA was improved when loaded into bovine milk-derived exosomes. While the in vitro results are encouraging, more in vivo testing in suitable animal models and biochemical marker analysis are warranted.

Evaluating the Efficacy and Safety of Antihypertensive Drugs in the Treatment of Congenital Heart Disease in Paediatric Patients: A Comprehensive Study

CHD is the most common of all congenital anomalies causing mortality among children, characterized by structural abnormalities present at birth that vary in severity and complexity. Increased cardiac workload due to CHD may stipulate a growth delay in the affected children. The complexity of treatment is further compounded by medication errors, and hence, rigorous strategies of evaluation and management become necessary. This study was conducted to determine antihypertensive drug consumption patterns and to evaluate their therapeutic efficacy among 92 patients with CHD to meet the evaluation criteria, including appropriateness of treatment for the condition of the patient, adherence to indications, accuracy of dosage, and drug use practice. Females constituted the highest proportion of patients at 53.26 percent, infants were the most common age group at 43.48 percent, and Atrial seal defect accounted for 22.5 percent of the CHD patients. The antihypertensive drugs predominantly prescribed are Furosemide, used by 44.9% of the subjects, followed by Captopril, used by 30.3%, and Spironolactone, used by 10.1%. Therapy was evaluated for its effectiveness; appropriateness, both for the patient's indications and drug usage, was found to be very high, at 98.9% and 97.8%, respectively, whereas adherence to prescribed dosage was relatively lower at 62.7%. This study points toward further challenges in the management of antihypertensive treatment among children with CHD. It needs combined efforts by a pediatric cardiologist, pharmacist, nurse, and caregiver for total care to reduce the risk from treatment. Continuous monitoring and alterations in the plan of treatment, coupled with education, could be significant in optimizing medication adherence to improve long-term health outcomes in CHD children. The research done in this field, at large, improves pediatric cardiology practice to reduce morbidity and mortality rates associated with congenital heart disease around the world.

Safety and efficacy of biologic drugs in children or adolescents with atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Children and adolescents suffering from moderate-to-severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p-value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08-8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71-10.02), EASI 50 (OR 8.89; 95% CI 6.18-12.78) and EASI 90 (8.30; 95% CI 4.81-14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34-9.90) or 4 points or more (OR 8.09; 95% CI 5.19-12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58-1.07), and conjunctivitis (OR 2.08; 95% CI 1.00-4.33). In this meta-analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population.

Real-world Disproportionality Analysis of the FDA Adverse Event Reporting System (FAERS) Database for Asciminib.

Asciminib is primarily utilized for treating Philadelphia chromosome-positive chronic myeloid leukemia in its chronic phase among patients harboring the T315I mutation or those who have been previously treated with at least two tyrosine kinase inhibitors. The safety profile of asciminib across a broad patient population over an extended timeframe remains unverified. This study uses a real-world pharmacovigilance database to evaluate the adverse events (AEs) linked with asciminib, providing valuable insights for clinical drug safety. Data from the FDA Adverse Event Reporting System (FAERS) database, spanning from October 2021 to December 2023, served as the basis for this analysis. The extent of disproportional events was assessed using sophisticated metrics such as the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. Within the specified period, the FAERS database documented 3,913,574 AE reports, with asciminib being associated with 966 incidents. Reactions to asciminib spanned 27 system organ categories. Utilizing four distinct analytical algorithms, 663 significant preferred terms exhibiting disproportional frequencies were identified. Notably, this investigation uncovered 26 significant AEs linked to off-label asciminib use, encompassing conditions such as gynecomastia, nephrotic syndrome, orchitis, pyelonephritis, hepatotoxicity, and pancreatitis. The median onset time for asciminib-related AEs was 52.5 days, ranging from 17 to 122.75 days.

Simultaneous Confidence Intervals for Signal Detection and Ascertaining Precision of Adverse Event Rates in Clinical Trials

The marketing authorization of a medicinal product is contingent upon demonstration of safety and efficacy in support of the product’s labeled conditions of use. To demonstrate safety, one group of adverse events that requires detailed consideration is common adverse reactions (ARs). ARs and their frequency are reported in prescription drug labeling in the US and EU. The determination of these adverse reactions generally takes a simple approach - usually, inclusion is through the frequency of reporting and whether the adverse event (AE) rate for the drug exceeds the placebo rate. This standard method does not account for confounders or multiplicity. To overcome these limitations, we propose a Monte-Carlo approach to detect drug safety signals in clinical trials. We fit regression models incorporating covariates to assess the drug effect on the rate of AEs. Adjustment for multiplicity is carried out through the construction of simultaneous confidence intervals accounting for arbitrary correlations. A computationally efficient multiplier bootstrap approach using the Rademacher sequences is developed to generate random samples from the joint distribution of the estimators for all the AE rates. Compared to Bonferroni-based methods, the proposed method leads to narrower simultaneous confidence intervals and is more powerful in detecting potential safety signals.

Phytochemical Composition and Bioactivities of Some Hydrophytes: Antioxidant, Antiparasitic, Antibacterial, and Anticancer Properties and Mechanisms

Few researches have explored the production of pharmaceuticals from aquatic plants. Therefore, this study explored, for the first time, the phytochemical composition and bioactivities of ten aquatic plants. Aquatic plant shoots from various Nile River canals were collected, dried, and ground for aqueous extract preparation. Phytochemical composition and antioxidant capacity were assessed using DPPH assays. Extracts were tested for antiparasitic, antibacterial, anti-biofilm, and anticancer activities through standard in vitro assays, measuring IC50 values, and evaluating mechanisms of action, including cell viability and high-content screening assays. The results showed that the aquatic plants were rich in pharmaceutical compounds. The antioxidant capacity of these extracts exceeded that of vitamin C. The extracts showed promising antiparasitic activity against pathogens like Opisthorchis viverrini and Plasmodium falciparum, with IC50 values between 0.7 and 2.5 µg/mL. They also demonstrated low MICs against various pathogenic bacteria, causing DNA damage, increased plasma membrane permeability, and 90% biofilm inhibition. In terms of anticancer activity, extracts were effective against a panel of cancer cell lines, with Ludwigia stolonifera exhibiting the highest efficacy. Its IC50 ranged from 0.5 µg/mL for pancreatic, esophageal, and colon cancer cells to 1.5 µg/mL for gastric cancer cells. Overall, IC50 values for all extracts were below 6 µg/mL, showing significant apoptotic activity, increased nuclear intensity, plasma membrane permeability, mitochondrial membrane permeability, and cytochrome c release, and outperforming doxorubicin. This study highlights the potential of aquatic plants as sources for new, safe, and effective drugs with strong antiparasitic, antibacterial, and anticancer properties.

Bioadhesive chitosan hydrogel with ROS scavenging promotes angiogenesis and mucosal repair for the treatment of gastric ulcer

Gastric ulcer (GU) is currently one of the most serious and common gastrointestinal diseases worldwide, severely affects the quality of life of patients. However, treatment strategies have limitations, such as drug safety and lack of repair specificity. In this work, we developed a polyethyleneimine/polyacrylic acid/lactose-modified chitosan (PPCL) hydrogel to repair gastric ulcers. This hydrogel was characterized by robust tissue adhesion, low swelling rate, gastric acid fluid resistance, potent antioxidants and good biocompatibility, which could act as a physical barrier to prevent gastric acid and digestive enzymes from further destroying ulcers. In vivo data from a rat GU model confirmed that this hydrogel effectively promoted gastric ulcer healing, and the therapeutic effect was better than that of commercial gastric mucosal protectants. Further mechanistic research identified that the hydrogel accelerated GU healing by alleviating oxidative stress, promoting reepithelization, angiogenesis and mucosal repair. Our findings revealed that the PPCL hydrogel provides a promising therapeutic approach for healing gastric ulcer.

Drug-associated porphyria: a pharmacovigilance study

BackgroundThe potentially fatal attacks experienced by porphyria carriers are triggered by various porphyrinogenic drugs. However, determining the safety of particular drugs is challenging.MethodsWe retrospectively used the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) to identify drugs associated with porphyria as an adverse event (AE) extracted from data from January 2004 to March 2022. The associated search terms included “Porphyria,” “Porphyria screen,” “Porphyria non-acute,” “Porphyria acute,” “Acquired porphyria,” and “Pseudoporphyria.” Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms, namely the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker.ResultsFAERS reported 1470 cases of porphyria-related AEs, and 406 drugs were screened after combining trade and generic names. All four algorithms identified 52 drugs with signals. The characteristics of all the reports and signaling drugs were analyzed.ConclusionsThis is the first report of drug-associated porphyria that provides critical information on drug porphyrogenicity, facilitating rational and evidence-based drug prescription and improving the accuracy of porphyrogenicity prediction based on model algorithms. Moreover, this study serves a reference for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.

Clinical efficacy and cost-effectiveness of metformin in different patient populations: A narrative review of real-world evidence.

Over the past two decades, diabetes pharmacopoeia has flourished, with new drugs that, on top of their glucose-lowering efficacy, have been shown to protect the heart and the kidney. Despite these new opportunities, metformin retains a pivotal role among glucose-lowering agents. As one of the few available insulin sensitizers, metformin is an effective, safe, and overall well-tolerated drug backed by over 60 years of clinical experience, including evidence for potential benefits beyond glucose reduction across different ages, sexes, genetic backgrounds, geographical areas, and stages of disease. Although there is some discussion of whether metformin offers the most effective front-line option in newly diagnosed type 2 diabetes (T2D), it remains a natural companion to all other glucose-lowering agents. Furthermore, metformin comes at a very low cost and, as such, it has extremely high cost-effectiveness, particularly given the serious economic burden associated with diabetes complications. This financial advantage is particularly relevant in resource-constrained healthcare systems, where the affordability of metformin may be instrumental in implementing an effective treatment in an evergrowing number of individuals. We present here compelling real-world evidence in support of the clinical efficacy and cost-effectiveness of metformin across different patient populations, highlighting areas where more population-based studies are needed to further incorporate and consolidate its use in the pharmacological management of T2D.

Long-term HBV infection of engineered cultures of induced pluripotent stem cell-derived hepatocytes.

HBV infects ~257 million people and can cause hepatocellular carcinoma. Since current drugs are not curative, novel therapies are needed. HBV infects chimpanzee and human livers. However, chimpanzee studies are severely restricted and cost-prohibitive, while transgenic/chimeric mouse models that circumvent the species barrier lack natural HBV infection and disease progression. Thus, in vitro human models of HBV infection are useful in addressing the above limitations. Induced pluripotent stem cell-derived hepatocyte-like cells mitigate the supply limitations of primary human hepatocytes and the abnormal proliferation/functions of hepatoma cell lines. However, variable infection across donors, deficient drug metabolism capacity, and/or low throughput limit iHep utility for drug development. We developed an optimal pipeline using combinations of small molecules, Janus kinase inhibitor, and 3',5'-cAMP to infect iHep-containing micropatterned co-cultures (iMPCC) with stromal fibroblasts within 96-well plates with serum-derived HBV and cell culture-derived HBV (cHBV). Polyethylene glycol was necessary for cell-derived HBV but not for serum-derived HBV infection. Unlike iHep monocultures, iMPCCs created from 3 iHep donors could sustain HBV infection for 2+ weeks. Infected iMPCCs maintained high levels of differentiated functions, including drug metabolism capacity. HBV antigen secretion and gene expression patterns in infected iMPCCs in pathways such as fatty acid metabolism and cholesterol biosynthesis were comparable to primary human hepatocyte-MPCCs. Furthermore, iMPCCs could help elucidate the effects of interferons and direct-acting antiviral drugs on the HBV lifecycle and any hepatotoxicity; iMPCC response to compounds was similar to primary human hepatocyte-MPCCs. The iMPCC platform can enable the development of safe and efficacious drugs against HBV and ultimately help elucidate genotype-phenotype relationships in HBV pathogenesis.

Deciphering Host-Parasite Interplay in Leishmania Infection through a One Health View of Proteomics Studies on Drug Resistance.

Recent efforts in the study of vector-borne parasitic diseases (VBPDs) have emphasized an increased consideration for preventing drug resistance and promoting the environmental safety of drugs, from the beginning of the drug discovery pipeline. The intensive use of the few available antileishmanial drugs has led to the spreading of hyper-resistant Leishmania infantum strains, resulting in a chronic burden of the disease. In the present work, we have investigated the biochemical mechanisms of resistance to antimonials, paromomycin, and miltefosine in three drug-resistant parasitic strains from human clinical isolates, using a whole-cell mass spectrometry proteomics approach. We identified 14 differentially expressed proteins that were validated with their transcripts. Next, we employed functional association networks to identify parasite-specific proteins as potential targets for novel drug discovery studies. We used SeqAPASS analysis to predict susceptibility based on the evolutionary conservation of protein drug targets across species. MATH-domain-containing protein, adenosine triphosphate (ATP)-binding cassette B2, histone H4, calpain-like cysteine peptidase, and trypanothione reductase emerged as top candidates. Overall, this work identifies new biological targets for designing drugs to prevent the development of Leishmania drug resistance, while aligning with One Health principles that emphasize the interconnected health of people, animals, and ecosystems.

MHRA Drug Safety Update - topical steroids.

MHRA Drug Safety Update - topical steroids.

N-demethylsinomenine metabolite and its prototype sinomenine activate mast cells via MRGPRX2 and aggravate anaphylaxis

Sinomenine hydrochloride (SH) is commonly used in the treatment of rheumatoid arthritis. It activates mast cells and induces anaphylaxis in the clinical setting. Adverse drug reactions can be caused by activation of MAS-associated G protein-coupled receptor X2 (MRGPRX2) on mast cells. Because the ligand binding site of MRGPRX2 is easily contacted in dilute solvents, it can be activated by many opioid drug structures. N-Demethylsinomenine (M-3) has a similar chemical structure to that of the opioid scaffold and is a major metabolite of SH. We sought to clarify whether M-3 induces anaphylaxis synergistically with its prototype in a mouse model. Molecular docking computer simulations suggested a similar binding effect between M-3 and SH. M-3 was chemically synthesized and analyzed by surface plasmon resonance to reveal its affinity for MRGPRX2. Temperature monitoring, in vivo hindlimb swelling and exudation test, and in vitro mast cell degranulation test were used to explore the mechanism of MRGPrx2 mediated allergic reaction triggered by M-3. Reduced M-3-induced inflammation was evident in MrgprB2 (the ortholog of MRGPRX2) conditional (Cpa3-Cre/MrgprB2flox) knockout (MrgprB2-CKO) mice. Additionally, LAD2 human mast cells with MRGPRX2 knockdown showed reduced degranulation. M-3 activated LAD2 cells synergistically with SH as regulated by GRK2 signaling and IP3R/PLC/PKC/P38 molecular signaling pathways. The results indicate that the M-3 metabolite can activate mast cells synergistically with its prototype SH via MRGPRX2 and aggravate anaphylaxis. These findings provide important insights into drug safety.

Description and Validation of a Novel AI Tool, LabelComp, for the Identification of Adverse Event Changes in FDA Labeling.

The accurate identification and timely updating of adverse reactions in drug labeling are crucial for patient safety and effective drug use. Postmarketing surveillance plays a pivotal role in identifying previously undetected adverse events (AEs) that emerge when a drug is used in broader and more diverse patient populations. However, traditional methods of updating drug labeling with new AE information have been manual, time consuming, and error prone. This paper introduces the LabelComp tool, an innovative artificial intelligence (AI) tool designed to enhance the efficiency and accuracy of postmarketing drug safety surveillance. Utilizing a combination of text analytics and a trained Bidirectional Encoder Representations from Transformers (BERT) model, the LabelComp tool automatically identifies changes in AE terms from updated drug labeling documents. Our objective was to create and validate an AI tool with high accuracy that could enable researchers and FDA reviewers to efficiently identify safety-related drug labeling changes. Our validation study of 87 drug labeling PDF pairs demonstrates the tool's high accuracy, with F1 scores of overall performance ranging from 0.795 to 0.936 across different evaluation tiers and a recall of at least 0.997 with only one missed AE out of 483 total AEs detected, indicating the tool's efficacy in identifying new AEs. The LabelComp tool can support drug safety surveillance and inform regulatory decision-making. The publication of this tool also aims to encourage further community-driven enhancements, aligning with broader interests in applying AI to advance regulatory science and public health.

Efficacy and safety of the polypeptide drug «Vesusten» in the correction of neurogenic LUTS in Multiple Sclerosis. Results of the pilot study

Efficacy and safety of the polypeptide drug «Vesusten» in the correction of neurogenic LUTS in Multiple Sclerosis. Results of the pilot study

Improving stereoselectivity of phosphotriesterase (PTE) for kinetic resolution of chiral phosphates

Specific stereoisomer is paramount as it is vital for optimizing drug efficacy and safety. The quest for the isolation of desired stereoisomer of active pharmaceutical ingredients or key intermediates drives innovation in drug synthetic and biocatalytic methods. Chiral phosphoramidate is an important building block for the synthesis of antiviral drugs such as remdesivir and sofosbuvir. Given the clinical potency of the (Sp)-diastereomer of the drugs, an enzyme capable of completely hydrolyzing the (Rp)-diastereomer is needed to achieve the purified diastereomers via biocatalytic reaction. In this study, protein engineering of phosphotriesterase (PTE) was aimed to improve the specificity. Employing rational design and site-directed mutagenesis, we generated a small library comprising 24 variants for activity screening. Notably, W131M and I106A/W131M variants demonstrated successful preparation of pure (Sp)-diastereomer of remdesivir and sofosbuvir precursors within a remarkably short hydrolysis time (&amp;lt;20 min). Our work unveils a promising methodology for producing pure stereoisomeric compounds, utilizing novel biocatalysts to enable the chemoenzymatic synthesis of phosphoramidate nucleoside prodrugs.

Investigation of Anti-inflammatory and Antioxidant Activities of Promising 1,4,5-Trisubstituted Pyrazoles Derivatives of Chalcone Ditosylates

Patients suffering from chronic pain and inflammatory disorders need novel COX-2 inhibitors to be developed with minimum toxicity to the kidneys, heart, and gastrointestinal tract and with excellent anti-inflammatory activity. The current study centers on an array of 1,4,5-trisubstituted pyrazoles produced via the reaction of ditosylates of chalcones with hydrochloride salt of phenylhydrazine. Chalcone was reacted with HTIB to produce a variety of derivatives of α, β chalcone ditosylates. Phenylhydrazine hydrochloride treatment of these chalcone ditosylates produced distinct 1,4,5-trisubstituted pyrazoles. The conversion process is mediated by 1,2-aryl migrations. IR, 1NMR, and elemental analysis were used to characterize the compounds after they had been purified by recrystallization. Using ascorbic acid as a reference, the DPPH (1,1-diphenyl-2-picrylhydrazyl) technique was used to assess the compounds' in vitro antioxidant activity. The paw edema technique caused by Carrageenan was utilized to assess the compounds' in vivo anti-inflammatory properties. The standard medication used was diclofenac sodium. A plethysmograph was used to measure the volume of the rats' paws. When compared to the standard, the compounds V5D5PH5 and V7D7PH7 showed modest antioxidant activity. When the synthetic pyrazoles were examined for their in vivo anti-inflammatory properties, substances V4D4PH4 and V7D7PH7 outperformed the reference. Here, we attempted to create new, safe, and effective drugs for the treatment of inflammatory disorders and pain by utilizing synthetic pyrazole moiety derivatives. Simple experimentation is used in the proposed study to improve pharmacological activity and yields. In the near future, chalcone ditosylate derivatives will be a powerful tool for selective modification.

The Essential Role of Traditional Chinese Medicine Compounds in Regulating Recurrent Spontaneous Abortion by Inhibiting Oxidative Stress.

Due to the lack of accurate registration of RSA and miscarriages, many early miscarriages are overlooked and not diagnosed or treated promptly in hospitals. This uncertainty in pathogenesis prevents clinicians from taking targeted therapeutic measures, leading to unsatisfactory treatment outcomes and placing a heavy burden on the patient's family and the healthcare system. Oxidative stress is present in embryonic development and affects the regulation of oxidative stress in pregnancy and the reproductive endocrine system. Oxidative stress injury is a significant pathogenesis of RSA, so improving the body's ability to resist oxidative stress injury is crucial in treating RSA. For patients with RSA, there is an urgent need for safe, efficient, and cost-effective anti-oxidative stress drugs, and there is growing evidence that treatment with Traditional Chinese medicine (TCM) can improve pregnancy success with fewer adverse effects. Many active ingredients for treating RSA are mainly derived from certain components of TCM, including flavonoids, phenols, and other compounds, which have been shown to treat RSA directly or indirectly by targeting anti-oxidative stress-related pathways. This article summarizes the experimental and clinical evidence of several common TCM compounds for treating RSA. It provides ideas and perspectives for further exploring the pathogenesis of RSA and TCM compounds for treating RSA.