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PloS One 2024In the search for better anticancer drugs, computer-aided drug design (CADD) techniques play an indispensable role in facilitating the lengthy and costly drug discovery...
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.
Topics: Anthraquinones; Humans; Neoplasms; Antineoplastic Agents; Drug Design; Molecular Docking Simulation; Computer-Aided Design; Drug Discovery
PubMed: 38776291
DOI: 10.1371/journal.pone.0301396 -
Marine Pollution Bulletin Jan 2024This study was conducted on the concentrations of PAHs, including benzo[a]pyrene and the sum of four PAHs (benz[a]anthracene, chryseno, benzo[b]fluoranthene, and...
This study was conducted on the concentrations of PAHs, including benzo[a]pyrene and the sum of four PAHs (benz[a]anthracene, chryseno, benzo[b]fluoranthene, and benzo[a]pyrene), in unsmoked fish tissues. The values were related to the time period, locality (country and region), living habits, eating habits, and types of environments of the fish species. The data obtained has been also compared with the limits established by the United States Environmental Protection Agency (U.S. EPA) and European Union (E.U.) legislation. The data were collected through a PRISMA systematic review (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) from 1982 to 2020. Only documents that presented the PAHs concentration values were selected. China, Nigeria, and Iran had the highest number of studies. The species Coptodon zillii, Siganus punctatus, and Liza abu were the most commonly used bioindicators. Fish inhabiting demersal and pelagic environments showed the highest concentrations of PAHs. The majority of PAH concentrations of the analyzed documents fell within permissible limits for human consumption, representing a total percentage of 79.49 % for benzo[a]pyrene and 82.86 % for the sum of the 4 PAHs. Although some studies identified concentrations of benzo[a]pyrene alone and benzo[a]pyrene, benz[a]anthracene, chryseno, benzo[b]fluoranthene above the legislation limits, in most of them, the concentrations reported in fish tissue were below the limits defined by European Legislation for human consumption.
Topics: Humans; Animals; Polycyclic Aromatic Hydrocarbons; Benzo(a)pyrene; Fluorenes; Anthracenes
PubMed: 38016205
DOI: 10.1016/j.marpolbul.2023.115778 -
BMC Cancer Sep 2023Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main...
BACKGROUND
Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart.
METHODS
A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed.
RESULTS
Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor.
CONCLUSIONS
Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.
Topics: Humans; Adolescent; Child; Cardiotoxicity; Mitoxantrone; Neoplasms; Heart; Anthracyclines; Polyketides
PubMed: 37710224
DOI: 10.1186/s12885-023-11353-9 -
Neurogastroenterology and Motility Nov 2023Over-the-counter supplements are commonly used to manage chronic constipation; however, their efficacy remains unclear. We aimed to investigate the effect of food,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Over-the-counter supplements are commonly used to manage chronic constipation; however, their efficacy remains unclear. We aimed to investigate the effect of food, vitamin or mineral supplements on stool output, gut transit time, symptoms, and quality of life in adults with chronic constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs).
METHODS
Studies were identified using electronic databases, backward citation, and hand-searching abstracts. RCTs reporting administration of food supplements (e.g., fruit extract supplements), vitamin or mineral supplements in adults with chronic constipation were included. Studies administering whole foods (e.g., fruits) were excluded. Risk of bias (RoB) was assessed with Cochrane RoB 2.0. Relative risks (RR), mean differences (MD), or standardized mean differences (95% confidence intervals [CI]) were calculated using a random-effects model.
KEY RESULTS
Eight RCTs (787 participants) were included, investigating kiwifruit (n = 3 RCTs), senna (n = 2), magnesium oxide (n = 2), Ziziphus jujuba (n = 1), and Malva Sylvestris (n = 1) supplements. Kiwifruit supplements did not impact stool frequency (MD 0.24 bowel movements/week [-0.32, 0.80]; p = 0.40) or consistency (MD -0.11 Bristol points [-0.31, 0.09], p = 0.29). Overall, 61% responded to senna and 28% to control; however, this did not reach statistical significance (RR 2.78, [0.93, 8.27]; p = 0.07). Overall, 68% responded to magnesium oxide and 19% to control (RR 3.32 [1.59, 6.92]; p = 0.001). Magnesium oxide improved stool frequency (MD 3.72 bowel movements/week [1.41, 6.03]; p = 0.002) and consistency (MD 1.14 Bristol points [0.48, 1.79]; p = 0.0007).
CONCLUSIONS AND INFERENCES
Magnesium oxide supplements are effective at improving cardinal symptoms of chronic constipation. Senna and kiwifruit supplements did not impact symptoms; however, findings were based on a small number of studies. Further research is required to investigate the effect of food supplements (e.g., kiwifruit supplements), as well as their whole food equivalents (e.g., whole kiwifruits) in chronic constipation.
Topics: Adult; Humans; Vitamins; Magnesium Oxide; Randomized Controlled Trials as Topic; Constipation; Sennosides; Dietary Supplements; Minerals; Actinidia
PubMed: 37243443
DOI: 10.1111/nmo.14613 -
Journal of Orthopaedic Surgery and... Apr 2023Knee osteoarthritis (KOA) is a common musculoskeletal condition affecting millions of people worldwide and posing a significant challenge to clinicians and researchers.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Knee osteoarthritis (KOA) is a common musculoskeletal condition affecting millions of people worldwide and posing a significant challenge to clinicians and researchers. Emerging evidence suggests that the multifaceted symptomatology of KOA may be alleviated by diacerein. With this in mind, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of diacerein in patients with KOA.
METHODS
We systematically searched Embase, PubMed, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), Wanfang Database (WanFang), China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) from their inception to August 2022 for randomized controlled trials (RCTs) of diacerein intervention on patients with KOA. Two reviewers independently performed the selection of eligible studies and the extraction of relevant data. The meta-analysis was performed using RevMan 5.4 and R 4.1.3 software tools. Depending on the type of outcome indicator selected, summary measures were expressed as mean differences (MD), standardized mean differences (SMD), or odds ratio (OR) with 95% confidence intervals (CI).
RESULTS
Twelve RCTs with 1732 patients were included. The results revealed that diacerein had comparable efficacy to non-steroidal anti-inflammatory drugs (NSAIDs) in reducing pain indicators such as Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (SMD = 0.09, 95% CI [-0.10, 0.28], P = 0.34) and visual analogue scale (VAS) (SMD = -0.19, 95% CI [-0.65, 0.27], P = 0.42). However, diacerein outperformed NSAIDs in terms of global efficacy assessment by both patients and investigators (patients: 1.97, 95% CI [1.18, 3.29], P = 0.01; investigator: 2.18, 95% CI [0.99, 4.81], P = 0.05) at the end of treatment and sustained effectiveness in reducing WOMAC score and VAS score at four weeks after treatment. Moreover, there was no significant difference in adverse events incidence between the diacerein and NSAID groups. However, the GRADE evaluation indicated that the majority of the evidence quality was low.
CONCLUSIONS
The results of this study suggest that diacerein could potentially be considered as a pharmacological agent with significant efficacy for the treatment of patients suffering from KOA, offering a potential alternative treatment strategy for those patients contraindicated to NSAIDs. However, further high-quality studies with longer follow-up are needed to make more informed decisions about its efficacy in the treatment of KOA.
Topics: Humans; Osteoarthritis, Knee; Pain; Anti-Inflammatory Agents, Non-Steroidal; Anthraquinones
PubMed: 37072810
DOI: 10.1186/s13018-023-03786-6 -
The Lancet. Oncology Mar 2023Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the... (Review)
Review
Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects of Childhood Cancer Guideline Harmonization Group.
Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the heart was exposed, are at increased risk of cardiomyopathy. Symptomatic cardiomyopathy is typically preceded by a series of gradually progressive, asymptomatic changes in structure and function of the heart that can be ameliorated with treatment, prompting specialist organisations to endorse guidelines on cardiac surveillance in at-risk survivors of cancer. In 2015, the International Late Effects of Childhood Cancer Guideline Harmonization Group compiled these guidelines into a uniform set of recommendations applicable to a broad spectrum of clinical environments with varying resource availabilities. Since then, additional studies have provided insight into dose thresholds associated with a risk of asymptomatic and symptomatic cardiomyopathy, have characterised risk over time, and have established the cost-effectiveness of different surveillance strategies. This systematic Review and guideline provides updated recommendations based on the evidence published up to September, 2020.
Topics: Child; Humans; Adolescent; Young Adult; Neoplasms; Survivors; Antibiotics, Antineoplastic; Cardiomyopathies; Mitoxantrone
PubMed: 37052966
DOI: 10.1016/S1470-2045(23)00012-8 -
Biomedicine & Pharmacotherapy =... May 2023The morbidity and mortality of cardiovascular diseases (CVDs) are increasing in recent years, and atherosclerosis (AS), a major CVD, becomes a disorder that afflicts... (Review)
Review
The morbidity and mortality of cardiovascular diseases (CVDs) are increasing in recent years, and atherosclerosis (AS), a major CVD, becomes a disorder that afflicts human beings severely, especially the elders. AS is recognized as the primary cause and pathological basis of some other CVDs. The active constituents of Chinese herbal medicines have garnered increasing interest in recent researches owing to their influence on AS and other CVDs. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a naturally occurring anthraquinone derivative found in some Chinese herbal medicines such as Rhei radix et rhizome, Polygoni cuspidati rhizoma et radix and Polygoni multiflori root. In this paper, we first review the latest researches about emodin's pharmacology, metabolism and toxicity. Meanwhile, it has been shown to be effective in treating CVDs caused by AS in dozens of previous studies. Therefore, we systematically reviewed the mechanisms by which emodin treats AS. In summary, these mechanisms include anti-inflammatory activity, lipid metabolism regulation, anti-oxidative stress, anti-apoptosis and vascular protection. The mechanisms of emodin in other CVDs are also discussed, such as vasodilation, inhibition of myocardial fibrosis, inhibition of cardiac valve calcification and antiviral properties. We have further summarized the potential clinical applications of emodin. Through this review, we hope to provide guidance for clinical and preclinical drug development.
Topics: Humans; Aged; Emodin; Drugs, Chinese Herbal; Cardiovascular Diseases; Plant Extracts; Atherosclerosis; Phytochemicals
PubMed: 36933375
DOI: 10.1016/j.biopha.2023.114539 -
Heliyon Dec 2022The present study investigated the contamination of processed cereals such as bread, spaghetti, flour, and bran, with polycyclic aromatic hydrocarbons (PAHs).
BACKGROUND
The present study investigated the contamination of processed cereals such as bread, spaghetti, flour, and bran, with polycyclic aromatic hydrocarbons (PAHs).
SCOPE AND APPROACH
The databases such as PubMed, Scopus, and Science Direct were searched from 14/December/1972 to 25/May/2021.
KEY FINDINGS
We identified 639 articles and selected 18. The highest PAH concentrations found in bread, spaghetti, flour, and bran were related to anthracene, chrysene, fluorene, and naphthalene, respectively. On the other hand, the lowest PAH concentrations found in bread, spaghetti, flour, and bran were related to benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, anthracene and dibenz[a,h]anthracene, respectively. Moreover, carcinogenetic and mutagenic risk assessment of the PAHs revealed a country-to-country variation. As a result, evaluation and control of PAHs in cereals should be done.
PubMed: 36536913
DOI: 10.1016/j.heliyon.2022.e12168 -
Medicine Nov 2022Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of diacerein in the treatment of osteoarthritis is controversial. We systematically reviewed the efficacy, safety, and residual effectiveness of diacerein.
OBJECTIVES
To estimate the symptomatic efficacy, residual effect and safety of diacerein in the treatment of knee osteoarthritis, using a meta-analysis of published randomized controlled trials (RCTs).
METHODS
On December 1, 2021, we searched PubMed Medline, Web of Science, Cochrane Library databases, Wan Fang Medical Database, and National Knowledge Infrastructure. This study followed the inclusion criteria of the principle P(Population), I(Intervention), C(Comparison), O(Outcome), S (Study design) principle. All studies were randomized controlled trials of knee osteoarthritis. Cochrane bias risk assessment tool was used to assess the risk of bias. Meta-analyses were performed using a random-effects model. To explore sources of heterogeneity, subgroup analysis, sensitivity analysis, regression analysis and publication bias analysis were performed. Drug side effects with complete data were extracted from the included articles and then a combined analysis of these data was performed.
RESULTS
Eight studies were eligible and were included in our analysis (N = 1277 participants). All studies were randomized controlled trials of knee osteoarthritis. There was no significant difference in reduction of joint pain and improvement of function between diacerein and the control group. However, subgroup analysis suggested, compared with the placebo group, diacerein treatment yielded an improved mean reduction in visual analogue scale score of-0.44% (95% confidence interval [CI]-0.79 to 0.09), an improved the western Ontario and McMaster universities (physical function) score of -0.44% (95% CI-0.72 to -0.12). Follow-up analysis after discontinuation showed that diacerein treatment had a significant residual effect (95% CI-0.81 to- 0.24). Data on drug side effects described in the included articles were extracted for statistical analysis. There was an increased risk of diarrhea with diacerein (Risk Ratio [RR] = 1.95 [1.03 to 2.47]) and withdrawal event from therapy (RR = 0.93 [0.75 to 1.15]).
CONCLUSION
Diacerein might be considered an effective drug for the treatment of patients with KOA, showing short-term residual effectiveness. Although it is associated with an increased risk of diarrhea, the adverse event is mostly tolerable.
Topics: Humans; Aged; Osteoarthritis, Knee; Anthraquinones; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Diarrhea; Randomized Controlled Trials as Topic
PubMed: 36401382
DOI: 10.1097/MD.0000000000031700 -
Phytomedicine : International Journal... Dec 2022Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of... (Review)
Review
BACKGROUND
Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products.
METHODS
A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria.
RESULTS
Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin.
CONCLUSION
Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9‑methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, β-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.
Topics: Acetates; Acrolein; Animals; Arbutin; Bleaching Agents; Cell Line, Tumor; Curcumin; Emodin; Flavonoids; Ginsenosides; Glucosides; Humans; Hydroxybenzoates; Melanins; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Phytochemicals; Plant Extracts; Pterocarpans; Stilbenes; Transcription Factors
PubMed: 36126406
DOI: 10.1016/j.phymed.2022.154449