Adverse Drug Effects Research Articles

Cross-lingual Natural Language Processing on Limited Annotated Case/Radiology Reports in English and Japanese: Insights from the Real-MedNLP Workshop.

Textual datasets (corpora) are crucial for the application of natural language processing (NLP) models. However, corpus creation in the medical field is challenging, primarily because of privacy issues with raw clinical data such as health records. Thus, the existing clinical corpora are generally small and scarce. Medical NLP (MedNLP) methodologies perform well with limited data availability. We present the outcomes of the Real-MedNLP workshop, which was conducted using limited and parallel medical corpora. Real-MedNLP exhibits three distinct characteristics: (1) Limited Annotated Documents: The training data comprises only a small set (approximately 100) of case reports (CRs) and radiology reports (RRs) that have been annotated. (2) Bilingually Parallel: The constructed corpora are parallel in Japanese and English. (3) Practical Tasks: The workshop addresses fundamental tasks, such as named entity recognition and applied practical tasks. We propose three tasks: named entity recognition (NER) of approximately 100 available documents (Task 1), NER based only on annotation guidelines for humans (Task 2), and clinical applications (Task 3) consisting of adverse drug effects (ADE) detection for CRs and identical case identification (CI) for RRs. Nine teams participated in this study. The best systems achieved 0.65 and 0.89 F1-scores for CRs and RRs in Task 1, whereas the top scores in Task 2 decreased by 50-70%. In Task 3, ADE reports were detected by up to 0.64 F1-score, and CI scored up to 0.96 binary accuracy. Most systems adopt medical-domain-specific pre-trained language models using data augmentation methods. Despite the challenge of limited corpus size in Tasks 1 and 2, recent approaches are promising because the partial match scores reached approximately 0.8-0.9 F1-scores. Task 3 applications revealed that the different availabilities of external language resources affected the performance per language.

Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.

Endocrine therapy is the standard treatment for hormone receptor-positive (HR+) breast cancer (BC). Yet, it is accompanied by treatment-related toxicities, leading to poor treatment adherence, high relapse, and low rates of survival. While pharmacogenomic variants have the potential to guide personalized treatment, their predictive value is inconsistent across published studies. To systematically assess the literature's current landscape of pharmacogenomics of endocrine therapy-related adverse drug effects, systematic searches in MEDLINE, Embase, Cochrane CENTRAL, Google Scholar and PharmGKB databases were conducted. We identified 87 articles. Substantial heterogeneity and variability in pharmacogenomic effects were evident across studies, with many using data from the same cohorts and predominantly focusing on the Caucasian population and postmenopausal women. Meta-analyses revealed Factor V Leiden mutation as a predictor of thromboembolic events in tamoxifen-treated women (p<0.0001). Meta-analyses also found that rs7984870 and rs2234693 were associated with musculoskeletal toxicities in postmenopausal women receiving aromatase inhibitors (p<0.0001 and p<0.0001, respectively). Overall, the current body of evidence regarding the potential role of pharmacogenomics in endocrine therapy-related toxicity in BC remains largely inconclusive. Key concerns include the heterogeneity in toxicity definitions, lack of consideration for genotype-treatment interactions, and the failure to account for multiple testing. The review underscores the necessity for larger and well-designed studies, particularly with the inclusion of premenopausal women and non-Caucasian populations.

A comprehensive assessment of the association between common drugs and psychiatric disorders using Mendelian randomization and real-world pharmacovigilance database

Medications prescribed for chronic diseases can lead to short-term neuropsychiatric symptoms, but their long-term effects on brain structures and psychiatric conditions remain unclear. We comprehensively analyzed the FDA Adverse Event Reporting System database and conducted drug target Mendelian Randomization (MR) studies on six categories of common drugs, 477 brain imaging-derived phenotypes (IDPs) and eight psychiatric disorders. Genetic instruments were extracted from expression quantitative trait loci (eQTLs) in blood, brain, and other target tissues, protein quantitative trait loci (pQTLs) in blood, and genome-wide association studies (GWAS) of hemoglobin and cholesterol. Summary statistics for brain IDPs, psychiatric disorders, and gut microbiome were obtained from the BIG40, Psychiatric Genomics Consortium, and MiBioGen. A two-step MR and mediation analysis were employed to screen possible mediators of drug-IDP effects from 119 gut microbiota genera and identify their mediation proportions. Among 19 drug classes, six drugs were found to be associated with higher risks of psychiatric adverse events, while 11 drugs were associated with higher risks of gastrointestinal adverse events in the FAERS analysis. We identified ten drug-psychiatric disorder associations, 202 drug-IDP associations, 16 drug-microbiota associations, and four drug-microbiota-IDP causal links. For example, PPARG activation mediated HbA1c reduction caused a higher risk of bipolar disorder (BD) II. Genetically proxied GLP-1R agonists were significantly associated with an increase in the volume of the CA3-head of the right hippocampus and the area of the left precuneus cortex, both of which have been shown to correlate with cognition in previous studies. Common drugs may affect brain structure and risk of psychiatric disorder. Oral medications in particular may exert some of these effects by influencing gut microbiota. This study calls for greater attention to be paid to the neuropsychiatric adverse effects of drugs and encourages drug repurposing. National Natural Science Foundation of China (grant No. 82330035, 82130043, 82172685, and 82001223), National Natural Science Foundation of Hunan Province (grant No. 2021SK1010), and the Science Foundation for Distinguished Young Scholars of Changsha (grant No. kq2209006).

Therapeutic Effects, Side Effects, and Adverse Effects of Neuropsychiatric Drugs in the Context of Treating Cancer-Related Anorexia With Olanzapine and Mirtazapine.

Drugs have actions that may be classified as therapeutic effects and side effects; side effects are actions that do not contribute to therapeutic benefit. Some side effects are neutral; others, experienced as undesirable or unpleasant, are recorded as adverse effects. Some drug actions are therapeutic for some disorders and adverse for others; or therapeutic during acute illness and adverse during maintenance treatment. As an example, anticholinergic action may be adverse when a tricyclic antidepressant is used to treat depression but therapeutic when the drug is used to treat irritable bowel syndrome with diarrhea. In clinical practice, side or adverse effects of a drug may be leveraged to manage troublesome symptoms. As an example, the sedative effect of a low dose of trazodone may be useful for some patients with insomnia. With this background, studies have examined whether the increase in appetite and weight associated with olanzapine and mirtazapine may be effective against anorexia and cachexia associated with cancer and cancer chemotherapy. The subject is important because cachexia may be present in 30%-50% of patients with cancer (with higher prevalence in patients with more advanced cancer) and because the presence of cachexia is associated with a higher risk of disease progression and mortality. Many randomized controlled trials (RCTs) have examined pharmacologic interventions such as progestins, corticosteroids, anamorelin, and medical cannabis for cancer related cachexia; most results have been disappointing. A recent RCT found that olanzapine (2.5 mg/d for 12 weeks) improved appetite, weight, other nutritional parameters, and quality of life in patients with locally advanced or metastatic cancer treated with chemotherapy. Another RCT, however, found that mirtazapine (30 mg/d for 8 weeks) brought no nutritional or anthropometric gain in patients with cancer and anorexia. It is concluded that olanzapine but not mirtazapine merits further investigation in patients with cancer who have anorexia and cachexia.

Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: a cross-sectional study

BackgroundOlder adults requiring care often have multiple morbidities that lead to polypharmacy, including the use of potentially inappropriate medications (PIMs), leading to increased medical costs and adverse drug effects. We conducted a cross-sectional study to clarify the actual state of drug prescriptions and the background of polypharmacy and PIMs.MethodsUsing long-term care (LTC) and medical insurance claims data in the Ibaraki Prefecture from April 2018 to March 2019, we included individuals aged ≥ 65 who used LTC services. The number of drugs prescribed for ≥ 14 days and the number of PIMs were counted. A generalized linear model was used to analyze the association between the backgrounds of individuals and the number of drugs; logistic regression analysis was used for the presence of PIMs. PIMs were defined by STOPP-J and Beers Criteria.ResultsHerein, 67,531 older adults who received LTC services were included. The median number of total prescribed medications and PIMs was 7(IQR 5–9) and 1(IQR 0–1), respectively. The main PIMs were loop diuretics/aldosterone antagonists (STOPP-J), long-term use of proton pump inhibitors (Beers Criteria), benzodiazepines/similar hypnotics (STOPP-J and Beers Criteria), and nonsteroidal anti-inflammatory drugs (STOPP-J and Beers Criteria). Multivariate analysis revealed that the number of medications and presence of PIMs were significantly higher in patients with comorbidities and in those visiting multiple medical institutions. However, patients requiring care level ≥1, nursing home residents, users of short-stay service, and senior daycare were negatively associated with polypharmacy and PIMs.ConclusionsPolypharmacy and PIMs are frequently observed in older adults who require LTC. This was prominent among individuals with comorbidities and at multiple consulting institutions. Utilization of nursing care facilities may contribute to reducing polypharmacy and PIMs.Graphical

Evaluation of nikkomycin Z with frequent oral administration in an experimental model of central nervous system coccidioidomycosis.

Coccidioides species are endemic fungi that are capable of causing disease in patients with various comorbidities, as well as in otherwise healthy individuals. Treatment options for coccidioidomycosis are suboptimal, as azole antifungals may be limited by drug interactions and adverse effects due to interactions with enzymes found in humans and other mammals. Nikkomycin Z is an investigational agent that works against a target specific to the fungal cell wall (chitin), which is not present in the cells of humans or other mammals. In this study, we show that frequent oral administration of nikkomycin Z is effective in an experimental model of central nervous system coccidioidomycosis. Further studies of nikkomycin Z against coccidioidomycosis may be warranted.

Proton Pump Inhibitor Prescription in Nursing Home Residents: Prevalence, Appropriateness, and Associated Factors-A Secondary Data Analysis from Three German Regions and the Impact of Guideline Recommendations.

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of "adequate" prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18-1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians' consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA.

Hyponatremia in geriatric patients.

Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (N = 2267, 1564 women, 703 men, mean age± standard deviation 81.9 ± 7.6years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77men; mean age± standard deviation 83.1 ± 7.3 years, p = 0.009 vs. age of all patients). Women had ahigher probability of developing hyponatremia compared to men (p = 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71patients.Only 12patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensinII receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was3 and the maximum number was7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive adiet with sufficient salt content.

(Invited) Cardiac Engineering: Optical Mapping in Cellular Communication

Microfluidic platforms have emerged as valuable tools for replicating the adverse effects of chemotherapy drugs on cardiac and non-cardiac cells in vitro. However, these systems currently fall short of comprehensively capturing the intricate nature of human responses to chemotherapy, necessitating further validation to enhance model accuracy. While innovative chip systems provide insightful means for screening cardiac toxicity, they encounter challenges in addressing individual variations in drug responses and the influence of patient-specific factors.A novel cardiac chip incorporating intracellular electrophysiological techniques was developed to monitor acute hypoxia-induced responses in cardiac cells. Despite its promising potential, the model exhibits limitations inherent to its simplified two-dimensional microfluidic system, warranting additional validation and optimization efforts to enhance physiological relevance and facilitate applications in clinical translation.Moreover, previous research has proposed the formation of functional connections between human neurons and myocardial cells in a microfluidic chip. However, this study primarily focused on one-way connections between neurons and myocardial cells, overlooking the complexities of bidirectional neuro-muscular connections. Consequently, further research is imperative to deepen our understanding of the intricate interactions between neurons and myocardial cells.Optical mapping techniques assessed transmembrane voltage, mitochondrial activity, and calcium signals during electric pacing. These comprehensive assessments aim to advance our understanding of cardiac electrophysiology under drug exposure, providing crucial insights into the intricate responses of cardiac cells to chemotherapy. This research has significant implications for enhancing our understanding of cardiac safety in the context of chemotherapy.

Using a Patient Portal to Screen Patients for Symptoms After Starting New Medications.

Conduct systematic proactive pharmacovigilance screening for symptoms patients experienced after starting new medications using an electronic patient portal. We aimed to design and test the feasibility of the system, measure patient response rates, provide any needed support for patients experiencing potentially drug-related problems, and describe types of symptoms and problems patients report. We created an automated daily report of all new prescriptions, excluding likely non-new and various over-the-counter meds, and sent invitations via patient portal inviting patients to inquire if they had started the medication, and if "yes," inquire if they had they experienced any new symptoms that could be potential adverse drug effects. Reported symptoms were classified by clinical pharmacists using SOC MeDra taxonomy, and patients were offered follow-up and support as desired and needed. Of 11,724 included prescriptions for 9360 unique patients, 2758 (29.4%) patients responded. Of 2616 unique medication starts, patients reported at least 1 new symptom that represented a potential adverse drug reaction (ADR) in 678/2616 (25.9%). Nearly one-third of those experiencing new symptoms (30.3%) reported 2 or more new symptoms after initiating the drug. GI disorders accounted for 30% of the total reported ADRs. Systematic portal-based surveillance for potential adverse drug reactions was feasible, had higher response rates than other methods (such as automated interactive phone calling), and uncovered rates of potential ADRs (roughly 1 in 4 patients) consistent with other methods/studies.

Self-Medication “Boon or Bane!!”: A Cross-Sectional Survey of Undergraduate Medical Students

Background: Self-medication can be a boon as well as curse to mankind whose proper application can reduce the unnecessary pressure on the health care system. The focus of this study was to assess the knowledge, attitude, and self-medication practices among undergraduate (UG) medical students, who are more likely to self-medicate themselves due to their limited knowledge and easy drug availability. Methods: The study involved distributing questionnaires among undergraduate medical students at Government Medical College, using a cross-sectional approach. The data was collected in June 2022, with 360 responses analyzed. The questionnaire, consisting of 17 close-ended questions, included demographics, prevalence, indications for self-medication, commonly self-medicated drugs, patterns of self-medication, and knowledge about safety and consequences. Results: 327 students willingly participated in the study of which 164 were females and 163 were males belonging to the age group of 18-25 years. The prevalence of self-medication was found to be 75.5%. Most common indication was cold, cough &amp; sore throat (70.4%) followed by headache (66%). Antipyretics (71.2%) and analgesics (62.3%) were most commonly used class of drugs. 84.5% students are aware about adverse effects of drugs. 74% opine that self-medication is not a good practice. Conclusion: Due to rising incidence of self-medication amongst the undergraduate medical students there is an increased risk of adverse drug effects. Thus, it is crucial to undertake measures that emphasize education and awareness, aiming to discourage self-medication among them.

A polifarmáciás idős betegek gyógyszerészi gondozásának gazdasági előnyei

The danger of polypharmacy (polypragmasia) lies in the fact that it usually affects older people who suffer from several chronic diseases and who are also less likely to medication adherence. For this reason, it is important to follow the drug therapy of these patients in the pharmacies, where feedback to general practitioners and specialists can take place in the event of a problem. For this reason, the development of pharmaceutical care is crucial. In the case of polypharmacy patients, inadequate drug therapy greatly increases the development of adverse drug effects and thus may increase mortality and morbidity indicators. Knowing the facts, it can be said that although pharmaceutical care involves additional costs, the adverse drug effects filtered out by it mean reduction in expenses.

Functional exosomes modified with chitosan effectively alleviate anthracycline-induced cardiotoxicity

Anthracyclines belong to a class of anti-tumor antibiotics, and their severe cardiotoxicity significantly limits their clinical use. Exosomes play key roles in intercellular communication, characterized by high biocompatibility and specific tissue and organ homing effects. In this study, doxorubicin, an anthracycline anticancer drug widely used in clinical chemotherapy, was selected as a model drug. To address the significant cardiotoxicity associated with doxorubicin, tumor exosomes are utilized as drug carriers. The homing effect of autologous exosomes enhances drug uptake by tumor cells and reduces cardiotoxicity. To enhance the stability of exosomes, improve therapeutic effectiveness, and reduce toxic side effects, chitosan was utilized to modify the surface of exosomes. Chitosan has a specific anti-tumor effect because it can target the CD44 receptor of tumor stem cells and interact with tumor cells through charge adsorption. Through in vitro cell experiments, in vivo pharmacokinetic experiments, and an in situ ectopic nude mouse tumor model, the study demonstrated that chitosan-modified tumor exosomes significantly alleviated the severe cardiotoxicity of doxorubicin, while also showing remarkable anti-tumor efficacy. This study introduces a novel approach to reduce the adverse side effects of anthracycline chemotherapeutic drugs and presents a highly promising nanocarrier delivery system.

Investigation of synergistic effect and mechanism of green tea extract and coffee extract on α‐amylase and α‐glucosidase inhibition

SummaryTo address the adverse effects of current hypoglycaemic drugs and the limited effect of individual extracts, this research investigated the inhibitory effect of combined green tea extract (GTE) and coffee (CE) on α‐amylase (α‐AMY) and α‐glucosidase (α‐GLU) and their inhibitory mechanisms. The inhibitory effects of single extracts and the complexes on α‐AMY and α‐GLU activities were compared by the principle of equivalence line. The results showed that the complexes had a good synergistic inhibition effect on both α‐AMY and α‐GLU at GTE: CE = 4:1 (w/w). Fluorescence spectroscopy and circular dichroism spectroscopy indicated that the complexes of GTE: CE = 4:1 (w/w) altered the secondary and tertiary structures of α‐AMY and α‐GLU more than the individual extracts, resulting in a synergistic inhibitory effect. The orthogonal experiments showed that tea polyphenols (TP) and coffee polyphenols (CP) were the main components responsible for the synergistic inhibitory effect of the two extracts.

Evaluation of the inhibitory effects of sitamaquine on Babesia infections

The treatment strategies for either human or animal babesiosis have been established and used for many years. With the rising indications of drug resistance and adverse side effects, finding effective and alternative therapies is urgently needed. Sitamaquine (SQ) is an 8-aminoquinoline that was first synthesized as a part of the collaborative anti-malarial program that led to primaquine. In this study, we evaluated the inhibitory effects of SQ on Babesia spp. in vitro and in vivo. The half-maximal inhibitory concentration (IC50) on in vitro cultured Babesia gibsoni was 8.04 ± 1.34 μM. Babesia gibsoni parasites showed degenerative morphological changes following SQ treatment. The in vivo growth inhibitory effects of SQ were evaluated in BALB/c mice infected with B. microti and atovaquone (ATV)-resistant B. microti strain. Oral administration of SQ at a dose of 20 mg/kg significantly inhibited the growth of B. microti and ATV-resistant B. microti. Meanwhile, SQ also showed inhibitory effects on the growth of B. rodhaini, a lethal rodent Babesia species. All mice infected with B. rodhaini treated with SQ survived, whereas the mice in the control group succumbed to the disease. The results obtained in this study indicate that SQ has potent inhibition effects against Babesia spp., which support SQ as a prospective alternative candidate for babesiosis treatment.

Risk of immediate postoperative fever in PFAPA patients undergoing tonsillectomy

ObjectivePeriodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. Tonsillectomy is considered a potential treatment option.A common concept is that patients with PFAPA are more likely to have postoperative fever, which might be hard to distinguish from other etiologies such as malignant hyperthermia or drug adverse effects. For this reason, many institutions require these patients to be cared for at their main center and not at satellite centers.Our objective was to evaluate the rate of immediate postoperative fever in PFAPA patients undergoing tonsillectomy. Material and methodsFollowing IRB approval (STUDY20060029), a retrospective chart review of all PFAPA patients who underwent tonsillectomy at a tertiary children's hospital between January 1st, 2013, and September 30th, 2022.The PHIS database was queried from January 1st, 2013, to June 30th, 2022, for pediatric tonsillectomy and PFAPA. ResultsSixty-one patients underwent tonsillectomy for PFAPA during the study period at our institution. Only one (1.6 %) had immediate postoperative fever. Fever episode resolution was seen in 90.25 % of patients, 41/41 (100 %) of the patients reported fever episodes pre-op, compared with 4/41 (9.75 %) post-op (McNemar's Chi-squared test, Chi2 = 37.0, p < 0.001).481,118 pediatric tonsillectomies were recorded in the PHIS database during this period, 1197 (0.25 %) were also diagnosed with PFAPA. None of the PFAPA patients had an immediate post-operative fever. ConclusionsOur results suggest there is no increased risk of immediate postoperative fever in PFAPA patients undergoing tonsillectomy.

Group 5 Pulmonary Hypertension: Multiple Systemic Diseases, Multiple Mechanisms of Pulmonary Hypertension, and Multiple Management Challenges

: Group 5 pulmonary hypertension (PH) with unclear and/or multifactorial mechanisms includes a wide variety of conditions associated with PH, and the mechanisms by which PH develops vary dramatically depending on the underlying condition. Indeed, in many group 5 conditions, such as sarcoidosis, multiple distinct drivers of PH are present concurrently in a single patient, with the predominant factor depending on the predisposing disease phenotype. For this reason, thorough diagnostic evaluation to most accurately phenotype every patient with group 5 PH is essential. Treatment of these patients should begin by fully characterizing and optimizing the management of their underlying disease, often in conjunction with disease experts. Initial targets of PH treatment include identifying and correcting factors that worsen PH, such as volume overload and hypoxemia, as well as a complete PH evaluation, searching for other undiagnosed causes of PH (e.g., congenital heart disease or chronic thromboembolic disease). Data to guide treatment with therapies specific to pulmonary arterial hypertension (PAH) are inadequate for any specific recommendations, and adverse effects in group 5 patients are common. If these therapies are considered, evaluation by a multidisciplinary team that includes a PH specialist is recommended. Factors in the selection of PAH therapies should include consideration of the dominant physiologic features of the underlying disease, the severity of hemodynamic and right ventricular abnormalities, the risk of adverse drug effects, and any known contraindications to PAH-specific medications based on the underlying condition. Vigilant monitoring following initiation of PAH-specific therapy is critical, as the clinical effects are hard to predict, and untoward events, such as uncovering pulmonary veno-occlusive disease, may occur. Collaborative care by a multidisciplinary team of experts is key to the management of this challenging patient population.

DNA/RNA heteroduplex technology with cationic oligopeptide reduces class-related adverse effects of nucleic acid drugs

Antisense oligonucleotides (ASOs) are a therapeutic modality for incurable diseases. However, systemic injection of gapmer-type ASOs causes class-related toxicities, including prolongation of activated partial thromboplastin time (aPTT) and thrombocytopenia. We previously reported that cholesterol-conjugated DNA/RNA heteroduplex oligonucleotides (Chol-HDOs) exhibit significantly enhanced gene silencing effects compared to ASOs, even in the central nervous system, through crossing the blood-brain barrier. In the present study, we initially evaluated the effect of the HDO structure on class-related toxicities. The HDO structure ameliorated the class-related toxicities associated with ASOs, but they remained to some extent. As a further antidote, we have developed artificial cationic oligopeptides, L-2,4-diaminobutanoic acid oligomers (DabOs), which bind to the phosphates in the major groove of A-type double helical structure of HDOs. DabO/Chol-HDO complex showed significantly improved aPTT prolongation and thrombocytopenia in mice while maintaining gene silencing efficacy. Moreover, the conjugation with DabOs effectively prevented cerebral infarction, a condition frequently observed in mice intravenously injected with high-dose Chol-HDO. These approaches, combining HDO technology with DabOs, offer distinct advantages over conventional strategies in reducing toxicities. Consequently, the DabO/HDO complex represents a promising platform for overcoming the class-related toxicities associated with therapeutic ASOs.

The contemporary issues related to conventional treatment of acne and the way forward

Background: People perceive acne as a minority disorder (not a major health concern), but it has a significant impact and burden on the victims. Although conventional drugs are available for its treatment, which are applied directly to the affected skin, such as azelaic acid, benzoyl peroxide, and salicylic acid etc. or formulationAcne vulgaris is a common skin condition that can have a significant impact on individuals, yet conventional treatments often come with various contemporary issues. This paper discusses the contemporary issues related to the conventional treatment of acne and explores a way forward. Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit, with a high prevalence globally and in Nigeria. Although conventional drugs are available for treatment, there are several contemporary issues related to their usage that need to be addressed. Method: Relevant literature, including stakeholder reports and studies conducted globally and locally, were searched and reviewed to identify the contemporary issues related to conventional acne treatment. The key contemporary issues identified include economic, environmental, emotional, social, and spiritual concerns. Findings: The economic burden of costly conventional medications makes them inaccessible for many. Environmental issues arise from the use of potentially harmful chemicals that can pollute water sources and contribute to climate change. Acne can also lead to emotional distress, social stigma, and spiritual conflicts, especially due to the side effects of conventional treatments. Given the limitations of conventional treatments, the article recommends the use of scientifically-proven herbal remedies as a promising alternative strategy. Herbs such as tea tree oil, green tea, chasteberry, black seed, and spikeweed have demonstrated antibacterial, anti-inflammatory, and anti-androgenic properties that can effectively manage acne without the adverse effects of conventional drugs. Conclusion: The use of evidence-based herbal medicines offers a way forward in the treatment of acne, addressing the contemporary issues associated with conventional approaches. Further clinical research and regulatory approval are necessary to integrate these herbal remedies into conventional acne management and ensure their widespread and safe use. Novelty/Originality of this article: This study proposes an integrated acne treatment framework that combines conventional therapies with evidence-based herbal medicine. This approach addresses contemporary issues in acne treatment by considering economic, environmental, and socio-cultural aspects.

Pyrones Isolated from Annona Acutiflora Exhibit Promising Cytotoxic Effects on Cancer Cell Lines.

This work discusses the ongoing challenge of cancer, focusing on therapy issues such as chemotherapy resistance and adverse drug effects. It emphasizes the need for new anticancer agents with improved efficacy and fewer side effects, exploring natural products from plant sources. The Annonaceae family, specifically the Annona genus, is highlighted for its medicinal properties, including anti-inflammatory and anticancer effects. The study focuses on the isolation and elucidation of the substances present in Annona acutiflora leaves. The methodology involves chromatographic and spectroscopy techniques. The isolated compounds, (6S)-5'-oxohepten-1'E,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (1), (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (2) and (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (3) were investigated for cytotoxicity assays on cancer cell lines and normal cells. Results show promising cytotoxic activity, particularly with compound 3, demonstrating potential activity against oral cancer (43.18 μM), hepatocarcinoma (17.24 μM), melanoma (5.39 μM), and colon cancer (59.03 μM). The compound outperforms carboplatin in selectivity against oral cancer (S. I. 2.15) and melanoma (S. I. 17.22). The study concludes by suggesting the potential of these α-pyrones as effective and less toxic alternatives for cancer therapy.