The Analgesic Potential of Litsea Species: A Systematic Review.

Various plant species from the Litsea genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the Litsea genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine Litsea species including (1) Litsea cubeba, (2) Litsea elliptibacea, (3) Litsea japonica, (4) Litsea glutinosa, (5) Litsea glaucescens, (6) Litsea guatemalensis, (7) Litsea lancifolia, (8) Litsea liyuyingi and (9) Litsea monopetala. Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HT1AR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the Litsea plants. Overall, the findings suggested Litsea species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.

Consensus holistic virtual screening for drug discovery: a novel machine learning model approach.

In drug discovery, virtual screening is crucial for identifying potential hit compounds. This study aims to present a novel pipeline that employs machine learning models that amalgamates various conventional screening methods. A diverse array of protein targets was selected, and their corresponding datasets were subjected to active/decoy distribution analysis prior to scoring using four distinct methods: QSAR, Pharmacophore, docking, and 2D shape similarity, which were ultimately integrated into a single consensus score. The fine-tuned machine learning models were ranked using the novel formula "w_new", consensus scores were calculated, and an enrichment study was performed for each target. Distinctively, consensus scoring outperformed other methods in specific protein targets such as PPARG and DPP4, achieving AUC values of 0.90 and 0.84, respectively. Remarkably, this approach consistently prioritized compounds with higher experimental PIC50 values compared to all other screening methodologies. Moreover, the models demonstrated a range of moderate to high performance in terms of R2 values during external validation. In conclusion, this novel workflow consistently delivered superior results, emphasizing the significance of a holistic approach in drug discovery, where both quantitative metrics and active enrichment play pivotal roles in identifying the best virtual screening methodology.Scientific contributionWe presented a novel consensus scoring workflow in virtual screening, merging diverse methods for enhanced compound selection. We also introduced 'w_new', a groundbreaking metric that intricately refines machine learning model rankings by weighing various model-specific parameters, revolutionizing their efficacy in drug discovery in addition to other domains.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A systematic review.

BACKGROUND: In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery process especially when natural products are involved. Anthraquinone is one of the most widely-recognized natural products with anticancer properties. This review aimed to systematically assess and synthesize evidence on the utilization of CADD techniques centered on the anthraquinone scaffold for cancer treatment. METHODS: The conduct and reporting of this review were done in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guideline. The protocol was registered in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904) and also published recently. The search strategy was designed based on the combination of concept 1 "CADD or virtual screening", concept 2 "anthraquinone" and concept 3 "cancer". The search was executed in PubMed, Scopus, Web of Science and MedRxiv on 30 June 2023. RESULTS: Databases searching retrieved a total of 317 records. After deduplication and applying the eligibility criteria, the final review ended up with 32 articles in which 3 articles were found by citation searching. The CADD methods used in the studies were either structure-based alone (69%) or combined with ligand-based methods via parallel (9%) or sequential (22%) approaches. Molecular docking was performed in all studies, with Glide and AutoDock being the most popular commercial and public software used respectively. Protein data bank was used in most studies to retrieve the crystal structure of the targets of interest while the main ligand databases were PubChem and Zinc. The utilization of in-silico techniques has enabled a deeper dive into the structural, biological and pharmacological properties of anthraquinone derivatives, revealing their remarkable anticancer properties in an all-rounded fashion. CONCLUSION: By harnessing the power of computational tools and leveraging the natural diversity of anthraquinone compounds, researchers can expedite the development of better drugs to address the unmet medical needs in cancer treatment by improving the treatment outcome for cancer patients.

Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recognized for their analgesic and anti-inflammatory properties. Amidst the SARS-CoV-2 pandemic, the role of NSAIDs in modulating viral and bacterial infections has become a critical area of research, sparking debates and necessitating a thorough review. This review examines the multifaceted interactions between NSAIDs, immune responses, and infections. Focusing on the immunomodulatory mechanisms of NSAIDs in SARS-CoV-2 and their implications for other viral and bacterial infections, we aim to provide clarity and direction for future therapeutic strategies. NSAIDs demonstrate a dual role in infectious diseases. They reduce inflammation by decreasing neutrophil recruitment and cytokine release, yet potentially compromise antiviral defense mechanisms. They also modulate cytokine storms in SARS-CoV-2 and exhibit the potential to enhance anti-tumor immunity by inhibiting tumor-induced COX-2/PGE2 signaling. Specific NSAIDs have shown efficacy in inhibiting viral replication. The review highlights NSAIDs' synergy with other medications, like COX inhibitors and immunotherapy agents, in augmenting therapeutic effects. Notably, the World Health Organization's analysis found no substantial link between NSAIDs and the worsening of viral respiratory infections. The findings underscore NSAIDs' complex role in infection management. Understanding these interactions is crucial for optimizing therapeutic approaches in current and future pandemics. However, their dual nature warrants cautious application, particularly in vulnerable populations. NSAIDs present a paradoxical impact on immune responses in viral and bacterial infections. While offering potential benefits, their usage in infectious diseases, especially SARS-CoV-2, demands a nuanced understanding to balance therapeutic advantages against possible adverse effects.

Assessing consumers' perception and demand on the community pharmacists' dispensing.

BACKGROUND: This study aimed to assess the general public's perception of services provided by community pharmacies, their willingness to utilize these services, their satisfaction with and understanding of community pharmacists, and their views on dispensing separation and pharmacy medicines (P medicines). METHODS: An online cross-sectional study was conducted, in which questionnaires were distributed among the general public. A novel questionnaire was designed and validated specifically for this study. It was composed of six sections: demographics, pharmacy usage and service preferences, understanding and satisfaction with pharmacists, views on dispensing separation, private community pharmacies, and knowledge of P medicines. Statistical analyses such as one-way ANOVA, independent t test, and binary logistic regression were employed, with a p value of < 0.05 considered statistically significant. RESULTS: The study received 222 responses. The majority of the respondents were females within the 20-29-year-old age group (62.2%). Most respondents preferred to consult doctors for medical treatment, with their primary reason for visiting community pharmacies being to collect prescribed medicines. About 52.7% of respondents expressed their willingness to avail of screening services and treatment for minor illnesses at community pharmacies. A statistically significant difference was found among different age groups regarding their views on the dispensing separation system, with those aged 41-50 years demonstrating higher scores. However, the binary logistic regression analysis did not reveal any statistical significance when comparing the understanding of P medicines among respondents. CONCLUSIONS: In general, the public prefers to consult doctors for medical treatment and visit community pharmacies predominantly to collect prescriptions or purchase over-the-counter medications. Nonetheless, they are also open to utilizing services provided by community pharmacists, particularly screening services and treatment for minor illnesses.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A protocol for systematic review.

There is still unmet medical need in cancer treatment mainly due to drug resistance and adverse drug events. Therefore, the search for better drugs is essential. Computer-aided drug design (CADD) and discovery tools are useful to streamline the lengthy and costly drug development process. Anthraquinones are a group of naturally occurring compounds with unique scaffold that exert various biological properties including anticancer activities. This protocol describes a systematic review that provide insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment. It was prepared in accordance with the "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 guidelines, and published in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904). Search strategies will be developed based on the combination of relevant keywords and executed in PubMed, Scopus, Web of Science and MedRxiv. Only original studies that employed CADD as primary tool in virtual screening for the purpose of designing or discovering anti-cancer drugs involving anthraquinone scaffold published in English language will be included. Two independent reviewers will be involved to screen and select the papers, extract the data and assess the risk of bias. Apart from exploring the trends and types of CADD methods used, the target proteins of these compounds in cancer treatment will also be revealed in this review. It is believed that the outcome of this study could be utilized to support the ongoing research in similar area with better quality and greater probability of success, consequently optimizing the resources in subsequent in vitro, in vivo, non-clinical and clinical development. It will also serve as an evidence based scientific guide for new research to design novel anthraquinone-derived drug with improved efficacy and safety profile for cancer treatment.

Identification and optimization of TDP1 inhibitors from anthraquinone and chalcone derivatives: consensus scoring virtual screening and molecular simulations.

Virtual screening aims to identify and rank compounds with drug/lead-like properties based on their affinity for the protein target. We developed a methodology that integrates structure- and ligand-based screening approaches to enhance hit rates against the TDP1 protein within a database of anthraquinone and chalcone derivatives, followed by evaluation of prioritized compounds through molecular simulations. This technique is particularly useful for training set imbalances. Four screening methods were used: QSAR, pharmacophore, shape similarity, and docking. Each method was individually trained to score compounds, and the scores were fused to create parallel Z-score fusion. The QSAR models exhibited satisfactory R2 values (0.84 to 0.75), whereas the pharmacophoric and shape similarity models demonstrated excellent performance (ROC:0.82-0.88). Docking enrichment analysis identified 6N0D as the optimal TDP1 crystal structure (ROC = 0.73). Remarkably, the consensus scoring method surpassed other screening methods, achieving the highest ROC value of 0.98. Docking screening prioritized compounds with binding modes resembling the co-crystallized ligands, whereas MMGBSA, consensus, and docking produced dynamic simulations that were as stable as the co-crystallized ligands. Additionally, the QSAR-selected compounds exhibited binding modes similar to those of commercially available TDP1 inhibitors. In this study, a strong correlation was found between the inhibitory concentrations and binding energy values of commercialized TDP1 inhibitors, indicating that the top-ranked compounds are expected to have potent inhibitory effects in the nano-/micromolar range. The results of this study establish that consensus scoring can be used as an adaptable mainstay virtual screening methodology, pending subsequent experimental validation for affirmation.Communicated by Ramaswamy H. Sarma.

Comparative analysis of potential drug-drug interactions in a public and private hospital among chronic kidney disease patients in Khyber Pakhtunkhwa: A retrospective cross-sectional study.

INTRODUCTION: Chronic kidney disease (CKD) is a significant public health challenge due to its rising incidence, mortality, and morbidity. Patients with kidney diseases often suffer from various comorbid conditions, making them susceptible to potential drug-drug interactions (pDDIs) due to polypharmacy and multiple prescribers. Inappropriate prescriptions for CKD patients and their consequences in the form of pDDIs are a major challenge in Pakistan. AIM: This study aimed to compare the incidence and associated risk factors of pDDIs among a public and private sector hospital in Khyber Pakhtunkhwa, Pakistan. METHOD: A retrospective cross-sectional study design was conducted to compare pDDIs among public and private sector hospitals from January 2023 to February 2023. Patients profile data for the full year starting from January 1 2022 to December 302022, was accessed All adult patients aged 18 years and above, of both genders, who currently have or have previously been diagnosed with end-stage renal disease (ESRD) were included. For assessing pDDIs, patient data was retrieved and checked using Lexicomp UpToDate® for severity and documentation of potential drug-drug interactions. RESULTS: A total of 358 patients' data was retrieved (with n = 179 in each hospital); however, due to incomplete data, n = 4 patients were excluded from the final analysis. The prevalence of pDDIs was found to be significantly higher in private hospitals (84.7%) than in public hospitals (26.6%), with a p-value <0.001. Patients in the age category of 41-60 years (AOR = 6.2; p = 0.008) and those prescribed a higher number of drugs (AOR = 1.2; p = 0.027) were independently associated with pDDIs in private hospitals, while the higher number of prescribed drugs (AOR = 2.9; p = <0.001) was an independent risk factor for pDDIs in public hospitals. The majority of pDDIs (79.0%) were of moderate severity, and a significant number of patients (15.1%) also experienced major pDDIs, with a p-value <0.001. The majority of pDDIs had fair documentation for reliability rating in both public and private hospitals. CONCLUSION: The prevalence of pDDIs was higher among CKD patients at private hospitals, and most of the pDDIs were of moderate severity. A considerable number of patients also experienced major pDDIs. The risk of experiencing pDDIs was found to be higher in older patients and among those prescribed a higher number of drugs.

Evaluating healthcare professionals' perceptions of dispensing separation and sale of pharmacy medicine in Brunei Darussalam.

BACKGROUND: Pharmacy medicine (P) is obtained exclusively from a pharmacy under the supervision of a pharmacist. This study aims to understand the perception of healthcare professionals towards the dispensing separation, as well as the dispensing of pharmacy medicine by community pharmacies to enhance patient health outcomes in Brunei Darussalam. METHODS: A cross-sectional study was conducted between 1st March 2023 and 20th April 2023 among healthcare professionals. A newly designed and validated questionnaire was used. Its face and content validity, along with internal consistency, was adequately established. Convenient sampling was employed to recruit participants for the study. Statistical analysis using one-way ANOVA was performed, considering a p-value < 0.05 as statistically significant. RESULTS: The study compiled data from 108 participants, comprising doctors (38.9%) and pharmacy technicians (45.4%). Approximately 28.7% of respondents had 11-20 years of healthcare experience, while 25.9% had less than 5 years. Nearly all respondents (98.1%) agreed on the vital role pharmacists and pharmacy technicians play in prescription checks. A significant number of participants (93.5%) agreed that Brunei's current medicine dispensing system needs improvement. The mean total score for the perception of medicine dispensing in Brunei was 3.79 ± 1.103. A statistically significant difference was found between the perception score and the respondents' profession (p = 0.018), but not with their age, experience, or place of work. Respondents' awareness score showed no statistically significant correlation with their profession, age, experience, or place of work. CONCLUSION: The study underscores the necessity for more patient-centered care in community pharmacies in Brunei Darussalam. The country's healthcare professionals should recognize the potential advantages of expanding pharmacy services. However, to implement these services successfully, regulatory restrictions and infrastructure limitations must be addressed.

Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management.

Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.

Diabetes Mellitus and Its Therapy in Brunei Darussalam - A Critical Revisit.

Introduction: Diabetes is becoming an increasingly common condition across the world including Brunei Darussalam. Bruneian population, although is relatively small, represents a miniature urban community of neighbouring Southeast Asian countries as they share similar dietary and ethnicity patterns. Thus, it would be valuable to examine the findings of studies conducted among Bruneians. This study aimed to identify and review research related to the practice of patients with DM in Brunei Darussalam in order to identify associated factors influencing diabetic medication knowledge and adherence. Methods: This narrative review analyzed literature related to DM and its therapy in Brunei Darussalam. Other issues consisting of knowledge and adherence related to DM were also explored. Databases (Scopus, PubMed, and Google Scholar) were used to search literature published up to May 2022. Search terms "diabetes mellitus", "Brunei" combined using Boolean operator were used. Results and Discussion: Conducting appropriate studies in Brunei Darussalam can benefit the government and policymakers to implement effective measures and programmes to combat the diabetes epidemic. Despite the government's efforts, additional relevant stakeholders must be included in order to work together and engage in these initiatives in order to increase diabetes awareness, give people the power to make healthy decisions, and ultimately reduce the prevalence of diabetes in Brunei Darussalam. Patients' medication knowledge proficiency plays a main component of ensuring appropriate and safe use of medication prescribed to them. Conclusion: Relatively poor medication knowledge and inappropriate diabetes-related practices were observed in studies conducted in Brunei Darussalam. However, no study has been done which directly measures both medication awareness and compliance among Brunei Darussalam T2DM patients. Future studies can focus on the relation between these two factors in different geographical locations of the world that are characterized by different diabetes-related practices and culture.

Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives.

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,ß-unsaturated system in the chalcone's rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.

Economic Analysis of Patient's Own Medication, Unit-Use and Ward Stock Utilization: Results of the First Pilot Study.

BACKGROUND: Medication wastage is causing a cost burden to the healthcare system that is worth millions of dollars. An economic and ecological friendly intervention such as using a patient's own medications (POM) has proven to reduce wastage and save the cost spent by the hospital. The potential benefits of using POM in inpatient settings have yet to be explored in a country with universal health coverage. This study aimed to pilot test the POM intervention in an adult ward setting and to perform the economic analysis of using POM and ward stock during hospitalization. METHODS: A prospective cross-sectional observational study was conducted among the patients admitted to the medical and surgical wards in a public hospital located in Brunei Darussalam between February 2022 and April 2022. Hospitalized adults above 18 years old with regular medications with a minimum length of stay of 48 h and a maximum length of stay of 21 days were included in the study. These eligible patients were divided into a POM group and a non-POM group. The economic analysis of using POM was performed by calculating the direct cost per unit of medication used during admission (from unit-use, ward stock and POM) and comparing the cost spent for both groups. Expired ward stock deemed as medication wastage was determined. Medical research ethics were approved, and all participating patients had given their written informed consent before enrolling in this study. RESULTS: A total of 112 patients aged 63.2 ± 15.8 years participated in this study. The average cost of medication supplied by the inpatient pharmacy for the non-POM group was USD 21.60 ± 34.20 per patient, whereas, for the POM group, it was approximately USD 13.00 ± 18.30 per patient, with a mean difference of USD 8.60 ± 5.17 per patient (95% CI: -3.95, 27.47, p ≥ 0.05). The use of POM minimized 54.03% (USD 625.04) of the total cost spent by the hospital for the POM group within the period of the study. CONCLUSION: The pilot study showed that the supplied medication cost per patient was not significantly different between the POM and non-POM groups. Nevertheless, the utilization of POM during hospitalization is capable of reducing at least 50% of the total cost spent on inpatient medications by the hospital. The use of POM during hospitalization also helped in reducing the total time spent on the medication process per patient.

Comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. A cheminformatics "proof-of-concept" study.

A Laplacian scoring algorithm for gene selection and the Gini coefficient to identify the genes whose expression varied least across a large set of samples were the state-of-the-art methods used here. These methods have not been trialed for their feasibility in cheminformatics. This was a maiden attempt to investigate a complete comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. This computational "proof-of-concept" study illustrated the combinatorial approach used to explain how the structure of the selected natural products (NPs) undergoes molecular diversity analysis. A virtual combinatorial library (1.6 M) based on 20 anthraquinones and 24 chalcones was enumerated. The resulting compounds were optimized to the near drug-likeness properties, and the physicochemical descriptors were calculated for all datasets including FDA, Non-FDA, and NPs from ZINC 15. UMAP and PCA were applied to compare and represent the chemical space coverage of each dataset. Subsequently, the Laplacian score and Gini coefficient were applied to delineate feature selection and selectivity among properties, respectively. Finally, we demonstrated the diversity between the datasets by employing Murcko's and the central scaffolds systems, calculating three fingerprint descriptors and analyzing their diversity by PCA and SOM. The optimized enumeration resulted in 1,610,268 compounds with NP-Likeness, and synthetic feasibility mean scores close to FDA, Non-FDA, and NPs datasets. The overlap between the chemical space of the 1.6 M database was more prominent than with the NPs dataset. A Laplacian score prioritized NP-likeness and hydrogen bond acceptor properties (1.0 and 0.923), respectively, while the Gini coefficient showed that all properties have selective effects on datasets (0.81-0.93). Scaffold and fingerprint diversity indicated that the descending order for the tested datasets was FDA, Non-FDA, NPs and 1.6 M. Virtual combinatorial libraries based on NPs can be considered as a source of the combinatorial compound with NP-likeness properties. Furthermore, measuring molecular diversity is supposed to be performed by different methods to allow for comparison and better judgment.

Cosmetics: What Do Bruneian Female Adults Believe?

OBJECTIVES: The study aimed to measure the level of attitudes and the current practices of the female community in Brunei Darussalam regarding the usage of cosmetics. METHODS: An online survey was conducted using a non-probabilistic snowball sampling approach via the social media channels WhatsApp and Instagram. The inclusion criteria were female Bruneian citizens or permanent residents, aged between 18 and 65 years old, who can understand English or Malay, and use cosmetic products at least once a day. RESULTS: A total of 445 participants responded to the online survey. Most of the participants agreed that the use of cosmetic products improves one's physical appearance to the public (391, 87.8%) and also improves self-confidence (405, 91.1%). There were significant differences in monthly cosmetic product expenses and participants' attitudes about safe cosmetic use (p = 0.001). No significant changes in the individuals' attitudes based on their age or educational level were observed. Overall, the participants had a good level of cosmetic safety practice. Almost half of the participants use social media to obtain information regarding what cosmetics to use or purchase. CONCLUSION: There is a medium to high level of attitude and a high level of practice regarding the safe use of cosmetics among Bruneian female adults. Social media was the main source of information for the respondents, followed by friend circle and family members.

Target-Based Small Molecule Drug Discovery for Colorectal Cancer: A Review of Molecular Pathways and In Silico Studies.

Colorectal cancer is one of the most prevalent cancer types. Although there have been breakthroughs in its treatments, a better understanding of the molecular mechanisms and genetic involvement in colorectal cancer will have a substantial role in producing novel and targeted treatments with better safety profiles. In this review, the main molecular pathways and driver genes that are responsible for initiating and propagating the cascade of signaling molecules reaching carcinoma and the aggressive metastatic stages of colorectal cancer were presented. Protein kinases involved in colorectal cancer, as much as other cancers, have seen much focus and committed efforts due to their crucial role in subsidizing, inhibiting, or changing the disease course. Moreover, notable improvements in colorectal cancer treatments with in silico studies and the enhanced selectivity on specific macromolecular targets were discussed. Besides, the selective multi-target agents have been made easier by employing in silico methods in molecular de novo synthesis or target identification and drug repurposing.

Medication Knowledge and Adherence in Type 2 Diabetes Mellitus Patients in Brunei Darussalam: A Pioneer Study in Brunei Darussalam.

AIM: The present study measured the medication knowledge and medication adherence in patients with type 2 diabetes in Brunei Darussalam. Demographic details and diabetes knowledge were also evaluated. METHODS: A cross-sectional study conducted via the administration of a structured questionnaire consisting of 4 sections via a face-to-face interview. RESULTS: A total of 118 participants were interviewed. A majority of the participants were aged 40 years or above (106, 89.8%). The mean number of total medications that the participants were taking was 7.36 ± 2.87 and the mean number of antidiabetic medications was 2.39 ± 1.06. As for the antidiabetic therapy, the largest proportion of the participants were taking oral antidiabetic medications only (87, 73.73%). In the diabetes knowledge section of the questionnaire, more than half of the participants (63, 53.34%) scored higher than the acquired mean score. Family history, education level, and total medications taken were significantly correlated with diabetes knowledge. However, in the medication knowledge section of the questionnaire, the mean score (3.37 ± 1.38) was below the intended score for good knowledge. Medication knowledge has been significantly associated with gender, family history and total medications taken. A majority of the participants reported non-adherence (74, 62.71%) due to various reasons. In this study, those of the Malay race were significantly correlated with adherence to their medication regimen. This study also revealed that there is no significant relationship between diabetes knowledge, medication knowledge and medication adherence. CONCLUSIONS: The present study provides insights in regard to patients with type 2 diabetes in Brunei Darussalam and their knowledge towards the disease as well as their medications. Despite the lack of significance between the variables, the rate of non-adherence is still alarming. Further studies are required to better understand the barriers to non-adherence in these patients.

Synergy between machine learning and natural products cheminformatics: Application to the lead discovery of anthraquinone derivatives.

Cheminformatics utilizing machine learning (ML) techniques have opened up a new horizon in drug discovery. This is owing to vast chemical space expansion with rocketing numbers of expected hits and lead compounds that match druggable macromolecular targets, in particular from natural compounds. Due to the natural products' (NP) structural complexity, uniqueness, and diversity, they could occupy a bigger space in pharmaceuticals, allowing the industry to pursue more selective leads in the nanomolar range of binding affinity. ML is an essential part of each step of the drug design pipeline, such as target prediction, compound library preparation, and lead optimization. Notably, molecular mechanic and dynamic simulations, induced docking, and free energy perturbations are essential in predicting best binding poses, binding free energy values, and molecular mechanics force fields. Those applications have leveraged from artificial intelligence (AI), which decreases the computational costs required for such costly simulations. This review aimed to describe chemical space and compound libraries related to NPs. High-throughput screening utilized for fractionating NPs and high-throughput virtual screening and their strategies, and significance, are reviewed. Particular emphasis was given to AI approaches, ML tools, algorithms, and techniques, especially in drug discovery of macrocyclic compounds and approaches in computer-aided and ML-based drug discovery. Anthraquinone derivatives were discussed as a source of new lead compounds that can be developed using ML tools for diverse medicinal uses such as cancer, infectious diseases, and metabolic disorders. Furthermore, the power of principal component analysis in understanding relevant protein conformations, and molecular modeling of protein-ligand interaction were also presented. Apart from being a concise reference for cheminformatics, this review is a useful text to understand the application of ML-based algorithms to molecular dynamics simulation and in silico absorption, distribution, metabolism, excretion, and toxicity prediction.

General Health Benefits and Pharmacological Activities of Triticum aestivum L.

Common wheat (Triticum aestivum), one of the world's most consumed cereal grains, is known for its uses in baking and cooking in addition to its medicinal uses. As this plant's medical benefits are enormous and scattered, this narrative review was aimed at describing the pharmacological activities, phytochemistry, and the nutritional values of Triticum aestivum. It is a good source of dietary fiber, resistant starch, phenolic acids, alkylresorcinols, lignans, and diverse antioxidant compounds such as carotenoids, tocopherols and tocotrienols. These constituents provide Triticum aestivum with a wide range of pharmacological properties, including anticancer, antimicrobial, antidiabetic, hypolipemic, antioxidant, laxative, and moisturizing effects. This review summarized the established benefits of wheat in human health, the mode of action, and different clinical, in vitro and in vivo studies for different varieties and cultivars. This review also gives an insight for future research into the better use of this plant as a functional food. More clinical trials, in vivo and in vitro studies are warranted to broaden the knowledge about the effect of Triticum aestivum on nutrition-related diseases prevention, and physical and mental well-being sustenance.

Cancer protective effects of plums: A systematic review.

Plums is one of the most cultivated stone fruits due to its fast growing popularity. It has various traditionally recognized health benefits. There are two main commercial types of plums: the European plum (Prunus domestica) and the Japanese plum (Prunus salicina), each having many varieties. Researchers are gathering further evidence of pharmacological effects for plums by scientifically studying its anti-inflammatory, antioxidant properties. A systematic review analysing the literature related to the effects of plums on prevention and treatment of cancer is warranted. This is the first review examining the cancer-related effects of plums. Antioxidation properties of the active constituents of plum were also compared. Scopus, Google Scholar, PubMed, Medxriv and Cochrane Library databases, from their date of inception until July 2021 were utilized. The risk of bias was assessed using CONSORT checklist. A total of 6639 studies were screened and eventually only 54 studies were included. Full-text review of included studies revealed that plum extracts were rich in antioxidants. Overall, most of the studies that fulfilled the eligibility criteria were in vitro and a few clinical studies involving in vivo work. Therefore, it would be beneficial to perform more studies on animals or humans, to confirm that the result obtained from these in vitro studies are able to be extrapolated in a wider range of applications. Further clinical and in vivo studies are warranted to validate plums as a functional food for treatment and prevention of cancer.