Current Medications Research Articles

Nitrogen-fused Heterocycles: Empowering Anticancer Drug Discovery.

The worldwide impact of cancer is further compounded by the constraints of current anticancer medications, which frequently exhibit a lack of selectivity, raise safety apprehensions, result in significant adverse reactions, and encounter resistance mechanisms. The current situation highlights the pressing need to develop novel and more precise anticancer agents that prioritize safety and target specificity. Remarkably, more than 85% of drugs with physiological activity contain heterocyclic structures or at least one heteroatom. Nitrogen-containing heterocycles hold a significant position among these compounds, emerging as the most prevalent framework within the realm of heterocyclic chemistry. This article explores the medicinal chemistry behind these molecules, highlighting their potential as game-changing possibilities for anticancer medication development. The analysis highlights the inherent structural variety in nitrogen-containing heterocycles, revealing their potential to be customized for creating personalized anticancer medications. It also emphasizes the importance of computational techniques and studies on the relationships between structure and activity, providing a road map for rational medication design and optimization. Nitrogen- containing heterocycles are a promising new area of study in the fight against cancer, and this review summarises the state of the field so far. By utilizing their inherent characteristics and exploiting cooperative scientific investigations, these heterocyclic substances exhibit potential at the forefront of pioneering therapeutic approaches in combating the multifaceted obstacles posed by cancer.

Abstract 4492: Deferiprone optimization for the treatment of triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is the leading cause of new cancer cases and the second leading cause of cancer deaths in American women disproportionately affecting Black and Hispanic women under 40. Currently, there is no targeted therapy for TNBC and treatment options to manage this lethal disease include surgery, adjuvant chemotherapy and radiotherapy. Among the chemotherapy agents, combination of the PARP inhibitors with DNA-damaging results in a more promising anti-tumor effect. A better understanding of TNBC etiology has aided in unraveling the roles of two additional cellular targets - androgen receptor (AR) and histone lysine demethylase (KDM) - in the viability and survival of TNBC. Interestingly, AR overexpression is the most important driver of prostate cancer (PCa). A class of current medications used to treat PCa act as androgen receptor (AR) antagonists (or antiandrogens). Antiandrogens are under investigation in the clinic as potential therapies for luminal AR (LAR) subtypes of TNBC, a particularly worrisome subtype that frequently metastasizes to regional lymph nodes and bones. Although LAR TNBC constitutes 15-20% of TNBCs, it is characterized by minimal response to chemotherapy and aggressiveness. It is therefore plausible to repurpose and optimize antiandrogens, in the context of designed multiple ligands; to obtain a TNBC-targeting therapy effective against several subtypes of this heterogenous disease, including the basal subtype that is responsible for ~80% of TNBC incidence. The proposed therapeutics are dual-acting antiandrogen-KDM inhibitors. The antiandrogen moiety of these agents will enable TNBC cell-targeting and translocation of the drug into the nucleus where inhibition of KDM will prevent transcription of KDMs that promote tumor growth. The three pharmacophores of these agents are (i) an AR binding group, (ii) a linker, and (iii) an iron-binding group. Two functional classes of these compounds, alkyl- and aryl-derivatives, vary in the design of the AR binding moiety. To optimize these agents, the methylene linker length is varied in each class for in vitro determination of the optimal length for increased drug efficacy. The compounds are tested on TNBC cell lines (MDA-MB-231, low AR+; and MDA-MB-453, high AR+), and ER+ BCa (MCF-7) while PCa cell lines (LNCaP PCa, AR+; and DU 145, PCa, AR-) serve as controls for AR dependency of the compounds. Longer linker length compounds exhibited low micromolar cytotoxicity and selectivity for AR+ TNBC and PCa cell lines. Further analysis of lead compounds in TNBC cells aided in understanding the effects on targets, transcriptomic effects via RNA sequencing analysis and the mechanism of action. Thus far, the designed dual-acting therapeutics have potential to revolutionize the design of anticancer drugs and improve treatment outcome for TNBC patients. Citation Format: Alexis Johnston, Adegboyega K. Oyelere. Deferiprone optimization for the treatment of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4492.

Can propensity score matching replace randomized controlled trials?

Randomized controlled trials (RCTs) have long been recognized as the gold standard for establishing causal relationships in clinical research. Despite that, various limitations of RCTs prevent its widespread implementation, ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria, amongst others. However, with the introduction of propensity score matching (PSM) as a retrospective statistical tool, new frontiers in establishing causation in clinical research were opened up. PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records, to create a matched sample of participants who received or did not receive the intervention based on their propensity scores, which takes into account characteristics such as age, gender and comorbidities. Given its retrospective nature and its use of observational data from existing sources, PSM circumvents the aforementioned ethical issues faced by RCTs. Majority of RCTs exclude elderly, pregnant women and young children; thus, evidence of therapy efficacy is rarely proven by robust clinical research for this population. On the other hand, by matching study patient characteristics to that of the population of interest, including the elderly, pregnant women and young children, PSM allows for generalization of results to the wider population and hence greatly increases the external validity. Instead of replacing RCTs with PSM, the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other. For example, in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial, the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol. Therefore, PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics, thus providing a fairer comparison for the impact of mannitol. This literature review reports the applications, advantages, and considerations of using PSM with RCTs, illustrating its utility in refining randomization, improving external validity, and accounting for non-compliance to protocol. Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients, while maintaining the robustness of randomization offered by RCTs.

Glucocorticoid-free remission in patients with SLE in the era of biologics: Immune complex disease is likely to benefit from current medications.

In addition to various immunosuppressive agents, belimumab and anifrolumab became available in Japan. We aimed to investigate glucocorticoid-free clinical remission in a single-centre retrospective cohort in October 2023. Our cohort included patients with SLE who needed to start or increase glucocorticoids for disease activity and were followed up for more than 1year. We investigated the rate of achievement of clinical remission off corticosteroids (CR off C), defined as no clinical score on the SLEDAI-2K without glucocorticoids, baseline predictors of CR off C, medications used when CR off C was achieved, and flare rates following CR off C. Out of the 60 patients followed for an average of 5.4 (±2.6) years, 17 (28.3%) achieved CR off C in 3.6 (±1.2) years after enrolment. Use of belimumab and anifrolumab accounted for eight (47.1%) of the achievers. Among the baseline data, male sex, recent enrolment, high glucocorticoid dose, and detection of immune complex (IC) significantly predicted CR off C, while lupus nephritis (LN) and a low C3 level tended to predict it. In the multivariate analysis, IC detection was the only predictor of CR off C. Clinical flares were observed in 5.9% of the achievers during a median 1.2years after achievement of CR off C. In the era of biologics, CR off C was achieved in 28.3% of the patient cohort requiring the start or increase of glucocorticoids for disease activity, with a relatively low rate of flares, suggesting that glucocorticoid-free clinical remission is an achievable target in SLE. IC disease, represented by male sex or nephritis, is likely to benefit from currently available medications.

Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye.

Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2X7R, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2X7R antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2X7R-NLRP3 inflammatory cascade to provide these benefits.

Mahuang Fuzi Xixin decoction alleviates allergic rhinitis by inhibiting NLRP3/Caspase-1/GSDMD-N-mediated pyroptosis

Ethnopharmacological relevanceAllergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. Aim of this studyThis study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis. MethodsMFXD, Mahuang, Fuzi, and Xixin water extracts were analyzed using ultra high performance liquid chromatography-Orbitrap-high-resolution accurate mass spectrometry. In in vivo study, the effects of MFXD on AR treatment were evaluated in an ovalbumin-induced mouse model. Mice were administered saline (control and model groups), MFXD (1.375, 2.75 g/kg), and dexamethasone (2.5 mg/kg) for 13 days. AR symptoms were evaluated by blinded observers. Immunoglobulin E (IgE) and histamine levels were measured using enzyme-linked immunosorbent assays. Expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 p10/p20, GSDMD-N and IL-1β) in AR mouse nasal mucosa were estimated by immunohistochemistry. In in vivtro study, the effects of MFXD on pyroptosis were assessed in human nasal epithelial cells (HNEpCs) stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and incubated with MFXD (12.5, 25, and 50 μg/mL). Pyroptosis-related protein expression was measured by western blotting. ResultsThirty-three compounds in MFXD were identified, including ephedrine, pseudoephedrine, higenamine, aconine, aconitine, benzoylmesaconitine, benzoylhypaconine and hypaconitine. In the in vivo study, oral taken of MFXD/dexamethasone significantly ameliorated AR symptoms, reduced swelling of the nasal mucosa, and decreased the levels of IgE and histamine in AR mice serum. MFXD/dexamethasone attenuated histopathological changes and reduced the expression of pyroptosis-related proteins in nasal mucosa, indicating the inhibitory effect on nasal epithelial pyroptosis. In the in vitro study, MFXD (50 μg/mL) significantly alleviated cytotoxicity, protected cells from swelling and rupture, and downregulated the expression of pyroptosis-related proteins in LPS/ATP-induced HNEpCs. ConclusionMFXD suppressed nasal epithelial pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD-N signaling pathway, which alleviates AR. Our results offer valuable insights into potential AR therapies and provide evidence for the clinical utilization of MFXD to treat AR.

Exploring epigenetic strategies for the treatment of osteoporosis.

The worldwide trend toward an aging population has resulted in a higher incidence of chronic conditions, such as osteoporosis. Osteoporosis, a prevalent skeletal disorder characterized by decreased bone mass and increased fracture risk, encompasses primary and secondary forms, each with distinct etiologies. Mechanistically, osteoporosis involves an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Current pharmacological interventions for osteoporosis, such as bisphosphonates, denosumab, and teriparatide, aim to modulate bone turnover and preserve bone density. Hormone replacement therapy and lifestyle modifications are also recommended to manage the condition. While current medications offer therapeutic options, they are not devoid of limitations. Recent studies have highlighted the importance of epigenetic mechanisms, including DNA methylation and histone modifications, in regulating gene expression during bone remodeling. The use of epigenetic drugs, or epidrugs, to target these mechanisms offers a promising avenue for therapeutic intervention in osteoporosis. In this review, we comprehensively examine the recent advancements in the application of epidrugs for treating osteoporosis.

Mortality in adults with sickle cell disease: Results from the sickle cell disease implementation consortium (SCDIC) registry.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus.

There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis-free approach that can measure thousands of exogenous chemicals in blood ("exposome") in patients with SLE and unaffected controls. This cross-sectional study analyzed a cohort of patients with prevalent SLE (n=285) and controls (n=106). Plasma was analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Mass spectrometry features present in at least 25% of all samples were selected for association analysis (n=2,737). Features were matched to potential chemicals using available databases. Association analysis of abundances of features with SLE status was performed, adjusting for age and sex. We also explored features associated with SLE phenotypes, sociodemographic factors, and current medication use. We found 30 features significantly associated with SLE status (Bonferroni P < 0.05). Of these, seven matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between patients with SLE and controls (Bonferroni P < 0.05). Two unmatched features were associated with a history of lupus nephritis, and one with anti-double-stranded DNA antibody production (Bonferroni P < 0.05). Seventeen features varied by self-reported race and ethnicity, including a polyfluoroalkyl substance (analysis of variance P < 1.69 × 10-5). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use. This proof-of-concept study demonstrates that LC-QTOF/MS is a powerful tool that agnostically detects circulating exogenous compounds. These analyses can generate hypotheses of disease-related exposures for future prospective, longitudinal studies.

Efficacy of nonpharmacological interventions for severe radiation-induced oral mucositis among head and neck cancer patients: A network meta-analysis of randomised controlled trials.

To assess the effectiveness of different nonpharmacological treatments for severe radiation-induced oral mucositis in patients with head and neck cancer. Radiation-induced oral mucositis is highly prevalent in patients with head and neck cancer. Current medications for radiation-induced oral mucositis are limited in effectiveness and susceptible to side effects, and while there is an increasing adoption of nonpharmacological interventions, the optimal one remains unclear. Systematic review and network meta-analysis based on the PRISMA-NMA guidelines. Six databases were searched. Two authors independently performed the literature screening, data extraction and methodological quality assessment of the included studies. Traditional pairwise meta-analysis was performed by R Studio. A network meta-analysis was then conducted to assess the effects of nonpharmacological interventions for severe radiation-induced oral mucositis in patients with head and neck cancer. Fifty-two studies involving seven types of nonpharmacological interventions were enrolled. The network meta-analysis indicated that natural plant-based therapies might be the most effective, health education interventions might be the second most effective, and honey might be the third most effective interventions for reducing the incidence of severe radiation-induced oral mucositis. For reducing the incidence of severe oral mucositis-related pain, the pairwise meta-analysis showed that only natural plant-based therapies and health education interventions were effective. Nonpharmacological interventions are effective in the management of severe radiation-induced oral mucositis among patients with head and neck cancer. Nonpharmacological interventions are a category of safe and effective adjunctive therapies that should be encouraged in clinical practice. CRD42023400745.

Digging deeper into pain: an ethological behavior assay correlating well-being in mice with human pain experience.

The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals.

PHARMACOKINETICS AND EFFICACY OF A SINGLE TOPICAL DOSE OF EPRINOMECTIN IN GIRAFFE (GIRAFFA SPP.).

Growing resistance to current antiparasitic medications, both in livestock and in zoological species under human care, makes it imperative to evaluate available drugs on the market, such as eprinomectin. In this prospective study, five males and one female of reticulated (Giraffa reticulata; n = 2), Masai (Giraffa tippelskirchii; n = 1), Nubian (Giraffa camelopardalis; n = 2), and hybrid subspecies (n = 1) of giraffe, received 1.5 mg/kg eprinomectin topically along the dorsum. Using high-performance liquid chromatography, concentrations of eprinomectin in plasma samples collected at 0, 4, 24, and 48 h, and 7, 14, 21, and 28 d were evaluated following drug administration. Complete blood cell counts and biochemistry panels were performed before (n = 6) and after (n = 3) eprinomectin administration. Samples for modified double centrifugal fecal flotation (n = 6) were evaluated prior to eprinomectin administration to evaluate for endoparasites and were repeated after the study (n = 5). Noncompartmental pharmacokinetic analysis was applied to the data. The observed maximum plasma concentration was 11.45 ng/ml and the time of observed maximum concentration was 2.67 d. The mean terminal half-life was 5.16 d. No adverse effects were observed related to eprinomectin administration and no blood work changes were observed. Parasite loads decreased (n = 3) or did not change (n = 2) after eprinomectin administration. The mean peak plasma concentration of eprinomectin in giraffe was similar to that achieved in cattle, despite using three times the dose.

Exercise Dependency and Overuse Injuries in Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is a common condition, but current medications have limitations, pushing a drive for alternative approaches. Different exercise-focused approaches have shown promise, but concern has also been raised about individuals with ADHD showing greater risk of addiction, including exercise dependency. Using an online survey, we examined current exercise practices, including exercise dependency and the presence of overuse injury, which could result from overexercising, in 114 adults with ADHD. We found that most were regularly exercising. None were classified as exercise dependent, but 38.9% were deemed symptomatic nondependent. Hyperactive-impulsive symptoms were a predictor of the level of exercise withdrawal experienced, and the co-occurrence of autism spectrum disorder was associated with greater risk of overuse injuries. The data indicate that ADHD may confer some greater risk of exercise dependency, aligning with previous studies investigating other addictions and suggesting further research is critical.

Anti-anxiety and Hypnotic Effects of Lawsonia inermis Hydroalcoholic Extract

Background: Sleep is a vital biological feature, and insomnia causes maladaptive physical and psychological functions. The main flaws of current insomnia medications are significant side effects. A suitable substitute can be herbal products. We aimed to evaluate the anti-anxiety, sleep-inducing, and - prolonging effects of Lawsonia inermis extract and fractions in mice. Methods: Male albino mice were pretreated intraperitoneally (i.p.) with either three doses (40, 80, and 160 mg/kg) of L. inermis extract or n-butanol fraction (NBF), ethyl acetate fraction (EAF), and water fraction (WF), 30 minutes before i.p. injection of 30 mg/kg pentobarbital. Sleep latency and duration of sleep were recorded. For anxiolytic activity, elevated plus-maze (EPM) tests were used. Moreover, the toxicity of the extract was determined in both in vivo and in vitro experiments. Results: L. inermis extract (160 mg/kg) significantly reduced sleep latency and increased sleep duration. EAF at 160 mg/kg decreased sleep latency and increased sleep duration. Flumazenil reversed the hypnotic effect of L. inermis extract (160 mg/kg). L. inermis extract (80, 160 mg/kg) increased the time spent and the number of entries in the open arms of EPM. The tested extracts and fractions administration found no adverse effects on PC12 cell viability. The LD50 was 2.4 g/kg. Conclusion: L. inermis extracts exhibit anxiolytic and hypnotic effects, probably modulating the GABAergic system.

Regenerative medicine for diabetes: Unraveling the impact of stem cells

Diabetes poses a significant health challenge, particularly in developing nations, with an alarming annual increase in cases. Current medications mainly focus on managing hyperglycemia and preventing complications associated with diabetes. However, the article underscores the potential of stem cells in advancing diabetes treatment, particularly in the generation of insulin-producing β-cells. It highlights the damage to these cells within the islet of Langerhans in diabetic patients, whether through autoimmune reactions in type 1 diabetes or inherent changes affecting β-cell function in type 2 diabetes. The article suggests that cell replacement strategies, such as islet transplantation, could offer therapeutic options for diabetes. Stem cells, capable of differentiating into specialized cells, are presented as a promising avenue for creating insulin-producing β-cells, aiming to restore normal insulin levels and providing a more comprehensive and long-term solution compared to current medications. While the potential is promising, it's essential to note that stem cell therapies are still in the experimental stage, necessitating further research and clinical trials to establish their safety and efficacy for widespread use in diabetes treatment.

Bee Sting Venom as a Viable Therapy for Breast Cancer: A Review Article.

Breast cancer is a kind of aggressive cancer that significantly affects women worldwide, thus making research on alternative and new therapies necessary. The potential impact of bee venom on breast cancer is the main subject of this analysis of this research article. Bee venom has drawn the attention of the world with the help of its constituent ingredients, namely the bioactive compounds, enzymes, and complex blend of proteins. They have a particularly varied chemical makeup and proven anti-cancer capabilities. This is a detailed review demonstrating the components of bee venom and their individual functions in fighting cancer, as well as the results of previously conducted in-vitro and in-vivo research. As described later, bee venom has given positive results in triggering apoptosis, preventing cell migration, inhibiting metastasis and invasion, and suppressing the existing breast cancer cells. It is found to have worked better along with the already existing chemotherapy treatments. These results were also proved with the help of various animal studies that showed reduced tumor development, reduced metastasis, and improved therapeutic effectiveness. Furthermore, certain studies and case reports from all over the world have exhibited consistent results in females affected by breast cancer. This study found that people receiving chemotherapy experienced improved health outcomes and reduced discomfort, with fewer negative side effects. It is important to conduct extensive research on the safety and effectiveness of this treatment because it is yet to be approved. The ideal dosage and administration methods must be explored in clinical trials. Moreover, it is imperative to evaluate the results of any combined treatments with current medications. There should be constant monitoring to prevent any potential side effects. Other important things like allergic reactions and hidden concerns should also be considered.

Unmet Needs in Psychodermatology: A Narrative Review.

Psychodermatology, the multidisciplinary field that explores the intricate interplay between the mind and the skin, has gained increasing recognition over the past decade. However, several knowledge gaps and unmet needs persist in the field. The objective of this narrative review was to investigate the unmet needs in the field of psychodermatology as they pertain to medical training, treatment, research, and care access. PubMed was searched from inception through December 2023 to identify articles related to psychodermatology. Findings revealed several unmet needs within the field of psychodermatology. First, there is a need for further investigation into the pathophysiology that links psychological stress to cutaneous disease including the development of novel therapies targeting key neuropeptides. Second, the existing literature focuses primarily on the pharmacologic treatment of body dysmorphic disorder and body-focused repetitive behaviors, as well as delusional parasitosis, for which the first-line agents are selective serotonin reuptake inhibitors and atypical antipsychotics, respectively. However, additional research into the efficacy and safety of the remaining psychotropic medications and the treatment of other common psychocutaneous diseases is required. Finally, there exists a significant gap in knowledge amongst clinicians tasked with treating psychocutaneous diseases. Dermatologists report low rates of training in psychodermatology and discomfort with prescribing psychotropic medications. In conclusion, increasing resources for dermatologist education on psychotropic agent use, development of new drugs targeting stress-induced skin conditions, and research on the psychocutaneous applications of current medications may greatly improve the quality and access of psychodermatology care.

Anti-Inflammatory Effect of Dental Pulpa Mesenchymal Stem Cell Exosomes Loaded Mucoadhesive Hydrogel on Mice with Dental Nickel Hypersensitivity.

In this study, the anti-inflammatory effect of dental pulp mesenchymal stem cell (MSCs) exosomes loaded to mucoadhesive hydrogel is investigated in a dental nickel hypersensitivity murine model. After culture of dental pulp MSCs in the third passage MSCs are loaded to a mucoadhesive hydrogel based on chitosan, cross-linked with genipin and modified with catechol groups. A dental nickel hypersensitivity model is created by administering NiCl2 and 10µg mL-1 lipopolysaccharide to 4-6 week-old Balb-c mice by intradermal injection. In mice treated with dental pulp MSC exosomes and exosomes in hydrogel, interferron gamma (IFN-γ) secreting CD4+T lymphocyte ratios significantly increase compared to the untreated group (p < 0.05). IFN-γ and interleukin 10 (IL-10) expression in buccal mucosa tissue sections and IFN-γ secreting CD4+T lymphocyte ratios are found to be significantly higher in mice treated with dental pulpa MSCs (DPMSCs) exosomes and DPMSCs exosomes in hydrogel compared to the untreated group (p < 0.05). According to flow cytometry results, IL-4 secreting CD4+T lymphocytes are found to be significantly decreased in DPMSCs exosomes group compared to dental nickel hypersensitivity group (p < 0.05). Administration of DPMSCs exosomes with mucoadhesive hydrogel may be an alternative to current medication in the treatment of dental nickel hypersensitivity.

Pharmacological Targeting of Ferroptosis in Cancer Treatment

A non-apoptotic iron-dependent form of Regulated Cell Death (RCD) known as ferroptosis is brought on by an excess of harmful lipid peroxides and iron overload. Inhibiting the antioxidant defense system results in overwhelming of GSH dependent pathway and building up iron-dependent Reactive Oxygen Species (ROS) that react with polyunsaturated fatty acids in large quantities can both cause ferroptosis. Recent research has shown that ferroptosis holds a great deal of promise for preventing tumor cell resistance and limiting growth and spread. Emerging evidence also suggests that ferroptosis plays a dual role in human cancer. However, the precise underlying molecular mechanisms and their different role in tumorigenesis are unclear. Therefore, in this review we summarize and briefly present the key pathways of ferroptosis, its dual role as an oncogenic and as a tumor suppressor event in human cancers, paying special attention to the regulation of ferroptosis along with a variety of current medications and naturally occurring substances that may one day be used to target ferroptosis in tumor cells. Thus, addressing this sort of cell death could be seen as a potentially expanding technique in cancer treatment. Consequently, this will offer crucial viewpoints for next research on ferroptosis-based cancer treatment.&#x0D; Keywords: Ferroptosis, antioxidant defense system, Cancer

A73 EVALUATING MENTAL HEALTH CONDITIONS IN YOUTH WITH INFLAMMATORY BOWEL DISEASE: A RETROSPECTIVE STUDY

Abstract Background Adolescents with chronic disease are at increased risk of psychosocial and socio-emotional challenges. During and after the COVID-19 pandemic, an increased prevalence of mental health conditions was observed in youth with chronic conditions. It is essential to understand the prevalence of mental health conditions in youth with Inflammatory Bowel Disease (IBD) to better support, advocate, and treat mental health conditions within a pediatric healthcare setting. Aims We aimed to determine the number and proportion of patients with IBD at McMaster Children’s Hospital (MCH) whose medical charts have documentation of 1) a mental health condition (generalized anxiety disorder (GAD), social anxiety disorder (SAD), eating disorder, major depressive disorder (MDD), suicidal ideation, attention deficit disorder and other) and/or 2) medication(s) used to treat mental health conditions. Methods Patients 12-17 years old with IBD who were treated in the pediatric Gastroenterology Clinic at MCH and had at least one appointment since June 4, 2022 were eligible. Medical records were reviewed to identify documented mental health conditions and patients’ current medications. The prevalence was then determined. Results Of 114 patients (77 male) (mean (SD) age 15.1 (1.6) years old), 33 (29%, n=20 males) had ≥ 1 recorded mental health condition: GAD (n=27, 82%), SAD (n=1, 3%), eating disorders (n=4, 12%), MDD (n=9, 27%), suicide ideations (n=5, 15%), attention deficit disorder (n=9, 24%), and other mental health conditions (n=1, 3%). Among the 33 patients with documented mental health conditions, 19 (58%) patients were taking medications related to mental health (Table I). Conclusions Our results estimate a 29% prevalence of mental health conditions in youth with IBD at MCH. A lack of mental health resources and screening protocols within this setting could result in an underrepresentation of adolescents with IBD and mental health comorbidities. Future studies will focus on incorporating screening methods for mental health conditions within pediatric healthcare settings to determine current barriers and accessibility to mental health supports. Table I. Medications in patients (n=33) with documented mental health condition Note Medications were prevalent in patients with ampersand:003E1 mental health diagnosis, thus frequency is lower than # of documented mental health diagnoses. *Other mental health conditions: borderline personality disorder and bipolar disorder with depression. Funding Agencies None