DARU Journal of Pharmaceutical Sciences最新文献

Background: Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer.

Methods: Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included.

Results: According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells.

Conclusion: Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

Background: Cancer treatment has improved over the past decades, but many cancer patients still experience adverse drug reactions (ADRs). Pharmacogenomics (PGx), known as personalized treatment, is a pillar of precision medicine that aims to optimize the efficacy and safety of medications by studying the germline variations. Germline variations in the DPYD lead to significant ADRs. The present cross-sectional study aims to evaluate the allele frequency of the DPYD gene variations in the Iranian population to provide insights into personalized treatment decisions in the Iranian population.

Methods: The allele frequency of 51 pharmacogenetic variations in the clinically relevant DPYD was assessed in a representative sample set of 1142 unrelated Iranian individuals and subpopulations of different ethnic groups who were genotyped using the Infinium Global Screening Array-24 BeadChip.

Results: The genotyping assay revealed eight pharmacogenetic variants including DPYD rs1801265 (c.85T > C; DPYD*9A), rs2297595 (c.496A > G), rs1801158 (c.1601G > A; DPYD*4), rs1801159 (c.1627A > G; DPYD*5), rs1801160 (c.2194G > A; DPYD*6), rs17376848 (c.1896T > C), rs56038477 (c.1236G > A; HapB3), and rs75017182 (c.1129-5923C > G; HapB3) with minor allele frequency (MAF) ≥ 1%.

Conclusion: The results of the study reveal significant genetic variations among Iranian population that could significantly influence clinical decision-making. These variants, with their potential to explain the substantial variability in drug response phenotypes among different populations, shed light on a crucial aspect of pharmacogenomics. These findings not only provide valuable insights but also inspire the design and implementation of future pharmacogenomic clinical trials, motivating further research in this crucial area.

Background: COVID-19 pandemic has turned our world upside down by meddling with our normal lives. While there is no definitive drug against SARS-CoV-2, antiviral drugs that are already in the market, are being repurposed against it, could now complete long-term as well as all age-specific investigations, and they are successful in saving millions of lives. Nevertheless, side-effects are emergingly seen in the patients undergoing treatment, and ineffectiveness is increasingly found due to the emerging notorious variants of the virus. Many of them are also facing serious co-infections including black fungus, Zika, and H1N1 virus to name a few.

Objectives: Therefore, this review highlights both drug resistance, their side-effects, and the significance for proper and long-term clinical trials of all age groups including children.

Methods: We have explored and proposed the mechanisms of drug resistance that may arise due to the misuse or overuse of drugs based on available experimental reports.

Results: The review provides solutions to the aforesaid issues of drug-resistance and side-effects by providing combination therapies, ancillary treatments, and other preventive strategies that can be useful in preventing drawbacks thereby curbing COVID-19 or similar future infections to maintain our normal lives.

Conclusion: COVID-19 and its long-term effects, if any, can be eradicated with strategic and mindful use of related therapeutics in a controlled manner.

Background: Several countries' most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored.

Objectives: To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish's initial development.

Methods: Zebrafish embryos 6-8 h post-fertilization (hpf) were exposed to different concentrations of ACM, MTZ, and NMS, separately, to obtain the 50% lethal concentrations (LC₅₀). Next, the embryos were exposed to distinct concentrations of the cocktail (LC₅₀/2, LC₅₀/5, LC₅₀/10, and LC₅₀/20) in a semi-static system. Samples were analyzed 0, 24, 48, and 96 h after exposure, and the drugs' concentrations in E3 medium were assessed by high-performance liquid chromatography. For embryotoxicity evaluation, the mortality, hatching, and heart rates; total length; and pericardial and yolk sac areas were determined. In addition, body malformations, edemas, presence of pigmentation, and histopathological assessments were also recorded.

Results: The LC₅₀ values obtained for MTZ, ACM, and NMS were 4.69 mgmL^-1, 799.98 μgmL^-1, and 0.92 μgmL^-1, respectively. No difference was observed between the drugs' nominal and observed concentrations at each time point. The cocktail significantly induced mortality and decreased hatching in the LC₅₀/10, LC₅₀/5, and LC₅₀/2 groups. Additionally, body malformations, pigmentation loss, and yolk sac and pericardial edemas were observed in the cocktail groups. The cocktail groups' larvae had decreased total length and slower heart rates compared to the controls (p < 0.05). The histopathological assessment showed that yolk sac edema promoted severe histological changes in the esophageal-intestine junction and intestine in larvae treated with cocktails. Moreover, PAS-positive structures decreased in the esophageal-intestine junction, intestine, and liver in larvae exposed to pharmaceutical cocktails.

Conclusion: This study's findings suggest the cocktail of ACM, MTZ, and NMS may be hazardous to aquatic organisms in case of environmental contamination.

Background: The analysis of how people search and "navigate" the internet to obtain health-related information and how they communicate and share this information can provide valuable knowledge about the disease patterns behaviour and health habits of populations.

Objective: To determine the population's interest in drug-related problems through information search trends.

Method: A descriptive ecological correlational study, based on obtaining Google Trends data.

Variables studied: relative search volume (RSV), evolution over time, milestones and seasonality.

Results: The most searched topic was drug overdose, with mean RSV of 56.25 ± 0.65. The highest increase occurred in the contraindication topic (R² = 0.87, p < 0.001). The main milestone was observed in the drug overdose topic in July 2018 (RSV = 100). A very close relationship was found between adverse drug reaction and contraindication (R = 0.89, p < 0.001). Slight seasonality was noted in the adverse drug reaction (augmented Dickey-Fuller test [ADF] = -1.96), contraindication (ADF = -2.66) and drug interaction (ADF = -1.67) topics, but did not show an epidemiological trend.

Conclusions: The greatest public interest was found in the drug overdose and contraindication topics, which showed a stronger upward trend, although the seasonality study did not show any very notable data or demonstrate epidemiological information search behaviour. The main milestone observed was due to media factors related to the consumption of narcotics. There was a clear difference in English-speaking countries in the use of the drug overdose topic. A correlation between the adverse drug reaction and contraindication topics was confirmed.

Background: Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways.

Objectives: Herein, using molecular hybridization strategy, we synthesized some new hybrid structures of Riluzole and DMF through some common successive synthetic pathways for evaluating their potential activity for remyelination in MS treatment.

Methods: Molecular docking experiments assessed the binding affinity of proposed structures to the NMDA active site. The designed structures were synthesized and purified based on well-known chemical synthesis procedures. Afterward, in vivo evaluation for their activity was done in the C57Bl/6 Cuprizone-induced demyelination MS model.

Results and conclusion: The proposed derivatives were recognized to be potent enough based on docking studies (ΔG_bind of all derivatives were -7.2 to -7.52 compare to the Ifenprodil (-6.98) and Riluzole (-4.42)). The correct structures of desired derivatives were confirmed using spectroscopic methods. Based on in vivo studies, D4 and D6 derivatives exhibited the best pharmacological results, although only D6 showed a statistically significant difference compared to the control. Also, for D4 and D6 derivatives, myelin staining confirmed reduced degeneration in the corpus callosum. Consequently, D4 and D6 derivatives are promising candidates for developing new NMDA antagonists with therapeutic value against MS disorders.

Background: Treatment management for opioid poisoning is critical and, at the same time, requires specialized knowledge and skills. This study was designed to develop and evaluate machine learning algorithms for predicting the maintenance dose and duration of hospital stay in opioid poisoning, in order to facilitate appropriate clinical decision-making.

Method and results: This study used artificial intelligence technology to predict the maintenance dose and duration of administration by selecting clinical and paraclinical features that were selected by Pearson correlation (filter method) (Stage 1) and then the (wrapper method) Recursive Feature Elimination Cross-Validated (RFECV) (Stage2). The duration of administration was divided into two categories: A (which includes a duration of less than or equal to 24 h of infusion) and B (more than 24 h of naloxone infusion). XGBoost algorithm model with an accuracy rate of 91.04%, a prediction rate of 91.34%, and a sensitivity rate of 91.04% and area under the Curve (AUC) 0.97 was best model for classification patients. Also, the best maintenance dose of naloxone was obtained with XGBoost algorithm with R² = 0.678. Based on the selected algorithm, the most important features for classifying patients for the duration of treatment were bicarbonate, respiration rate, physical sign, The partial pressure of carbon dioxide (PCO₂), diastolic blood pressure, pulse rate, naloxone bolus dose, Blood Creatinine(Cr), Body temperature (T). The most important characteristics for determining the maintenance dose of naloxone were physical signs, bolus dose of 4.5 mg/kg, Glasgow Coma Scale (GCS), Creatine Phosphokinase (CPK) and intensive care unit (ICU) add.

Conclusion: A predictive model can significantly enhance the decision-making and clinical care provided by emergency physicians in hospitals and medical settings. XGBoost was found to be the superior model.

Background: It has been reported that High-Fructose (HF) consumption, considered one of the etiological factors of Metabolic Syndrome (MetS), causes changes in the gut microbiota and metabolic disorders. There is limited knowledge on the effects of metformin in HF-induced intestinal irregularities in male and female rats with MetS.

Objectives: In this study, we investigated the sex-dependent effects of metformin treatment on the gut microbiota, intestinal Tight Junction (TJ) proteins, and inflammation parameters in HF-induced MetS.

Methods: Fructose was given to the male and female rats as a 20% solution in drinking water for 15 weeks. Metformin (200 mg/kg) was administered by gastric tube once a day during the final seven weeks. Biochemical, histopathological, immunohistochemical, and bioinformatics analyses were performed. Differences were considered statistically significant at p < 0.05.

Results: The metformin treatment in fructose-fed rats promoted glucose, insulin, Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR), and Triglyceride (TG) values in both sexes. The inflammation score was significantly decreased with metformin treatment in fructose-fed male and female rats (p < 0.05). Moreover, metformin treatment significantly decreased Interleukin-1 Beta (IL-1β) and Tumor Necrosis Factor-Alpha (TNF-α) in ileum tissue from fructose-fed males (p < 0.05). Intestinal immunoreactivity of Occludin and Claudin-1 was increased with metformin treatment in fructose-fed female rats. HF and metformin treatment changed the gut microbial composition. Firmicutes/Bacteroidetes (F/B) ratio increased with HF in females. In the disease group, Bifidobacterium pseudolongum; in the treatment group, Lactobacillus helveticus and Lactobacillus reuteri are the prominent species in both sexes. When the male and female groups were compared, Akkermansia muciniphila was prominent in the male treatment group.

Conclusion: In conclusion, metformin treatment promoted biochemical parameters in both sexes of fructose-fed rats. Metformin showed a sex-dependent effect on inflammation parameters, permeability factors, and gut microbiota. Metformin has partly modulatory effects on fructose-induced intestinal changes.