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Panax ginseng is a common natural product, which is well-known to have a wide range of pharmacological activities in cancer. Its metabolite, compound K (CK), has been reported to have anticancer activity. We aimed to systematically review the literature for evidence of anticancer effects of CK. We conducted a systematic search in eight databases. We included all in vitro and in vivo studies investigating the anticancer effects of CK with no restrictions. Quality assessment was applied by ToxRTool. Fifty-four articles were included in our study. The purity of CK in our included studies was at least 95%. The in vitro studies reported that CK had a potential anticancer activity on several cell lines including human lung cancer cell lines (A549, PC-9), nasopharyngeal carcinoma cell line (Hk-1), liver cancer cell line (BEL 7402), and pediatric acute myeloid leukemia cell lines (Kasumi-1, MV4-11). The in vivo studies reported a significant decrease in tumor volume in mice treated with CK. CK is a potential supplementary treatment in cancer chemotherapies. The safety and further clinical trials of CK should be explored for future drug development., Fundamental & Clinical Pharmacology, pp.1-29; 2023. doi:10.1111/fcp.12874

The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by in vitro studies since there are concerns related to interference with their active sites.

Background: Emergence of cross-resistance to current anti-malarial drugs has led to an urgent need for identification of potential compounds with novel modes of action and anti-malarial activity against the resistant strains. One of the most promising therapeutic targets of anti-malarial agents related to food vacuole of malaria parasite is haemozoin, a product formed by the parasite through haemoglobin degradation. Methods: With this in mind, this study developed two-dimensional-quantitative structure–activity relationships (QSAR) models of a series of 21 haemozoin inhibitors to explore the useful physicochemical parameters of the active compounds for estimation of anti-malarial activities. The 2D-QSAR model with good statistical quality using partial least square method was generated after removing the outliers. Results: Five two-dimensional descriptors of the training set were selected: atom count (a_ICM); adjacency and distance matrix descriptor (GCUT_SLOGP_2: the third GCUT descriptor using atomic contribution to logP); average total charge sum (h_pavgQ) in pKa prediction (pH = 7); a very low negative partial charge, including aromatic carbons which have a heteroatom-substitution in “ortho” position (PEOE_VSA-0) and molecular descriptor (rsynth: estimating the synthesizability of molecules as the fraction of heavy atoms that can be traced back to starting material fragments resulting from retrosynthetic rules), respectively. The model suggests that the anti-malarial activity of haemozoin inhibitors increases with molecules that have higher average total charge sum in pKa prediction (pH = 7). QSAR model also highlights that the descriptor using atomic contribution to logP or the distance matrix descriptor (GCUT_SLOGP_2), and structural component of the molecules, including topological descriptors does make for better anti-malarial activity. Conclusions: The model is capable of predicting the anti-malarial activities of anti-haemozoin compounds. In addition, the selected molecular descriptors in this QSAR model are helpful in designing more efficient compounds against the P. falciparum 3D7A strain., Malaria Journal, 20, art. no. 264; 2021

Background: Systematic reviews (SRs) and meta-analyses (MAs) are commonly conducted to evaluate and summarize medical literature. This is especially useful in assessing in vitro studies for consistency. Our study aims to systematically review all available quality assessment (QA) tools employed on in vitro SRs/MAs. Method: A search on four databases, including PubMed, Scopus, Virtual Health Library and Web of Science, was conducted from 2006 to 2020. The available SRs/MAs of in vitro studies were evaluated. DARE tool was applied to assess the risk of bias of included articles. Our protocol was developed and uploaded to ResearchGate in June 2016. Results: Our findings reported an increasing trend in publication of in vitro SRs/MAs from 2007 to 2020. Among the 244 included SRs/MAs, 126 articles (51.6%) had conducted the QA procedure. Overall, 51 QA tools were identified; 26 of them (51%) were developed by the authors specifically, whereas 25 (49%) were pre-constructed tools. SRs/MAs in dentistry frequently had their own QA tool developed by the authors, while SRs/MAs in other topics applied various QA tools. Many pre-structured tools in these in vitro SRs/MAs were modified from QA tools of in vivo or clinical trials, therefore, they had various criteria. Conclusion: Many different QA tools currently exist in the literature; however, none cover all critical aspects of in vitro SRs/MAs. There is a need for a comprehensive guideline to ensure the quality of SR/MA due to their precise nature., BMC Medical Research Methodology, 21, art. no. 101; 2021

Background Morinda morindoides has been used as herbal medicine in Africa for a long time. It possesses potential therapeutic activities such as antiplasmodial, antispermatogenic, anti-bacterial, anti-fungal, anti-diarrheal effects, stomach pain and constipation reliefs. However, there has been no literature summarising its potential effects. This study therefore aims to systematically review the therapeutic activities of this medicinal plant as well as its pharmacological activities. Materials and methods Nine databases were selected to search suitable articles namely MEDLINE (PubMed), ISI, Scopus, Google Scholar, Global Health Library (GHL), Virtual Health Library (VHL), POPLINE, New York Academy of Medicine gray Literature Report (NYAM), and System for Information on gray Literature in Europe (SIGLE). Based on inclusion and exclusion criteria, we included 54 papers for the systemic review. Results Briefly, in vitro studies showed that M. morindoides possessed anti-malarial, anti-bacterial, anti-fungal, anti-amoebic, anti-larval, spasmolytic, anti-oxidant effects and complementary modulation. Moreover, those effects were emphasized in animal studies. The plant also showed positive activities on body metabolism studied on animal models such as hypotensive, hypoglycemic, hypolipidemic actions. M. morindoides showed its safety on animals’ organs as it did not dramatically change in blood parameters or injure cardiac tissues. However, there were many inconsistent results from various studies in terms of its benefits while its extracts showed a wide range of safety on different cells. Conclusion M. morindoides has proven to have potential therapeutic effects in vitro and in vivo models. Therefore, higher quality studies on human are necessary to be conducted, which can provide stronger evidence to confirm M. morindoides’s effects.

Dengue is classified as an endemic infectious disease, which is transmitted by Aedes mosquitos. Kinetic studies, which monitor the viral load of the disease, have been the mainstay for several decades in humanity's quest to control this disease. Our study aims to systematically evaluate the usage of different timing systems in dengue kinetic studies. A search in nine electronic databases and manual search of reference and citation lists were conducted to find relevant studies. A quality assessment using the National Institute of Health tools for observational cohort and cross-sectional studies was performed. The protocol was registered in PROSPERO with number CRD42018086435. As results, among included 87 studies, 71 studies (81.6%) use a timing system which is based on the day of illness onset, of which, 11 studies designate the day of illness onset as "day 0″ (type 1A) while 60 studies designate it as "day 1″ (type 1B). Only ten articles (11.5%) designate the day of defervescence as "day 0″, the day before and after defervescence as "day -1″ and "day +1″, respectively. Four articles (4.6%) use a timing system based on the day of hospital admission. Lastly, two studies (2.3%) designate the day of hemorrhagic manifestation as "day 0″ and two studies (2.3%) designate the day of pharmacological treatment as "day 1″. Therefore, the timing system which designates the day of illness onset as "day 1″ (type 1B) was most commonly used. Inconsistent definitions of "day 0″ and "day 1″ may lead to disparities in results across the studies and may have a negative impact on treatment guidelines implementation.

Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte abnormalities, and acid-base disturbance. These adverse effects of diuretics predispose patients to serious cardiac arrhythmias and may increase the risk of arrhythmic mortality. Herein, we aim to summarize the relative efficacy and safety of all available diuretics used in the treatment of patients with HF. In June 2017, a systematic electronic database search was conducted in nine databases. All randomized controlled trials (RCTs) comparing the different diuretics used in HF were included for meta-analysis. The protocol was registered in Prospero with CRD42018084819. Among the included 54 studies (10,740 patients), 34 RCTs were eligible for quantitative network meta-analysis (NMA) and traditional meta-analysis while the other 20 studies were qualitatively analyzed. Our results showed that azosemide and torasemide caused a significant reduction in brain natriuretic peptide (BNP) level. Torasemide also caused a significant decrease in collagen volume fraction (CVF) and edema. No significant difference between the agents concerning glomerular filtration rate (GFR), water extraction, and sodium excretion was demonstrated. Regarding side effects, no significant difference among diuretics was observed in terms of hospital readmission and mortality rates. Diuretics are the main treatment of hypervolemia in HF patients. The choice of appropriate diuretic is essential for successful management and is mainly guided by patient clinical situations and the presence of other co-morbidities.

Background Despite noticeable improvement in anti-malarial treatment, rapid growth of resistant malaria strains points out the need for continuous development of novel anti-malarials to fight the disastrous infection. Haemozoin is considered as a novel inhibitory pathway for new anti-malarial drugs, therefore, this study aimed to systematically review all articles investigating the correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds. Methods A literature search was conducted on 22 October 2017 in eight databases for relevant in vitro articles reporting the correlation between anti-malarial and anti-haemozoin of anti-malarial compounds, based on the constructed search terms and inclusion criteria. ToxRtool was used to assess quality of each study. Results A total of ten articles were included in the review. In vitro anti-malarial and anti-haemozoin activity had a good correlation for quinolines for sensitive strains (R2 ranging from 0.66 to 0.95) and xanthones (Spearman ρ = 0.886). However, these correlations were reached after removing some compounds which had non-detectable anti-malarial or anti-haemozoin effects. Other structures (acridines, pyrolidines) showed negligible correlation with Spearman ρ ranging from 0.095 to 0.381 for acridines, and r varying from 0.54 to 0.62 for pyrolidines. Some good correlations were only shown in a logarithmic manner or when the anti-malarial activity was normalized. Conclusion The results raised a relative relationship between anti-haemozoin and in vitro anti-malarial activities. Some studies reported compounds that were effective in the inhibition of haemozoin formation, but failed to inhibit the parasite survival and vice versa. The correlation results in these studies were calculated after these compounds were removed from their analysis. The ability of anti-malarial compounds to accumulate inside the reaction site might strengthen their anti-malarial activity.

Background Optimizing sleep has been recently gained exposure as a promising lifestyle consideration to aid in the control of diabetes. The evidence to support the impact of sleep quantity and quality on blood glucose control is largely acknowledged. This study aimed to review all published randomized controlled trials (RCTs) investigating the relationship between sleep and glucose control to synthesize an accurate overview. Method Literature from PubMed and Google Scholar was searched using the listed search terms to obtain RCTs on the role of sleep in glucose homeostasis. Seven RCTs were eligible and included in our review. References in these RCTs were screened for the presentation of the pathophysiology of metabolic disturbances relating to the sleep duration, and the relevant factors affecting blood glucose concentration. Results Sleep deprivation and poor sleep quality are connected with blood glucose disturbance and reduction of insulin sensitivity. This leaves diabetic patients at an increased risk of glucose level fluctuations. However, the function of β-cells was likely to be conserved after 14-days of sleep deprivation. Sleep extension from 7 to 14 days improved blood glucose control and insulin sensitivity in both healthy and diabetes participants. Diabetes sleep education and personalized interventions that reduced stress and improved sleep quality contributed to glucose homeostasis in diabetic patients. Overall improving one’s sleep hygiene was found to improve glucose control in diabetic patients. Conclusion Longer or short-term sleep deprivation may negatively affect glucose homeostasis, although the body temporarily compensates for the impaired function of β-cells when reduced sleep lasted up to 14 days. Thus, we recommend optimum sleep duration and optimistic sleep duration and sleep quality for decreasing risk and progression of diabetes.

Background:Mulberry, including several species belonging to genus Morus, has been widely used as a traditional medicine for a long time. Extracts and active components of mulberry have many positive neurological and biological effects and can become potential candidates in the search for new drugs for neurological disorders.Objectives:We aimed to systematically review the medical literature for evidence of mulberry effects on the central nervous system.Methods:We conducted a systematic search in nine databases. We included all in vivo studies investigating the effect of mulberry on the central nervous system with no restrictions.Results:We finally included 47 articles for quality synthesis. Our findings showed that mulberry and its components possessed an antioxidant effect, showed a reduction in the cerebral infarct volume after stroke. They also improved the cognitive function, learning process, and reduced memory impairment in many animal models. M. alba and its extracts ameliorated Parkinson's disease-like behaviors, limited the complications of diabetes mellitus on the central nervous system, possessed anti-convulsant, anti-depressive, and anxiolytic effects.Conclusion:Mulberry species proved beneficial to many neurological functions in animal models. The active ingredients of each species, especially M. alba, should be deeper studied for screening potentially candidates for future treatments

Losing weight has significant impact on chronic disease management. Orlistat, a lipase inhibitor, has alternative effect for weight controlling. To find more candidates, we conducted a review of chalcone and xanthine derivatives regarding their anti-lipase activity. Eight databases were searched including PubMed, Scopus, Web of Science (ISI), Virtual Health Library (VHL), System for Information on Grey Literature in Europe (SIGLE), Global Health Library (GHL), EMBASE, and Google Scholar in August 2018. We found chalcone scaffold was more effective on lipase inhibition than xanthine scaffold. Among 19 investigated chalcones, only isoliquiritigenin and licuroside demonstrated an effect on preventing weight gain and increase in the total cholesterol and total triglycerides aside apart from their high activity on inhibiting lipase. Effect and type of inhibition of individual chalcones differed depending on their structure. In addition, very few studies investigated xanthine compounds and their activities were inconsistent. We suggest more studies investigate the ability of chalcones and modifying their structure to find out other compounds with higher efficacy.

The COVID-19 pandemic has caused millions of deaths and hundreds of millions of confirmed infections worldwide. This pandemic has prompted researchers to produce medications or vaccines to reduce or stop the progression and spread of this disease. A variety of previously licensed and marketed medications are being tested for the treatment and recurrence of SARS-CoV2, including favipiravir (Avigan). Favipiravir was recognized as an influenza antiviral drug in Japan in 2014, and has been known to have a potential in vitro activity against SARS-CoV-2, in addition to its broad therapeutic safety scope. Favipiravir was recently approved and officially used in many countries worldwide. Our review provides insights and up-to-date knowledge of the current role of favipiravir in the treatment of COVID-19 infection, focusing on pre-clinical and ongoing clinical trials, evidence of its efficacy against SARS-CoV-2 in COVID-19, side effects, anti-viral mechanism, and the pharmacokinetic properties of the drug in the treatment of COVID-19. Due to its teratogenic effects, favipiravir cannot be offered to expectant or pregnant mothers. The practical efficacy of such an intervention regimen will depend on its dose, treatment duration, and cost as well as difficulties in application.

Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of ginsenoside Rh1 in a systematic manner. We performed searches on eight electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE, Global Health Library, Virtual Health Library, the System for Information on Grey Literature in Europe, and the New York Academy of Medicine Grey Literature Report to select the original research publications reporting the biological and pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies regardless of publication language and study design. Upon applying the inclusion and exclusion criteria, we included a total of 57 studies for our systemic review. Ginsenoside Rh1 exhibited the potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on different types of cell lines. Other pharmacological effects including estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the consistent efficacy of ginsenoside Rh1.

Objectives In this study, we aim to review researchers' reporting practices of the ethics statement, financial incentives, and local ethical committees' profile in their clinical trials. Study Design and Setting A systematic search was done through top-ranked 50 medical journals (Scimago Ranking) to retrieve 2,000 latest publications. Only primary clinical trials were included with no restriction to language or participants. Results Among the 927 included trials, 14 trials (1.5%) did not report an ethical statement and two-third (63%) did not completely report the investigated components (Institutional Review eBoard approval, Helsinki Declaration, and informed consent). Moreover, 21 trials (2.26%) reported motivational incentives with the method and amount of payment for participants. Of them, 15 trials offered monetary incentives to participants in different forms. In the remaining six trials, the incentives were mainly medical benefits. Only one trial reported the profile or quality of local Institutional Review Board. Conclusion A potential gap in the reporting practices of ethics statement and financial incentives was addressed in this review. Authors are urged to fully report all ethical components related to their study, including incentives and compensations plan. Medical journals are also recommended to implement further publication requirements concerning ethics reporting.

Background: The massive abundance of studies relating to tropical medicine and health has increased strikingly over the last few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-analysis (SR/MA) is considered a feasible solution for keeping clinicians abreast of current evidence-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a step-by-step approach mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance. We suggest that all steps of SR/MA should be done independently by 2-3 reviewers' discussion, to ensure data quality and accuracy. Conclusion: SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, full-text screening, manual searching, extracting data, quality assessment, data checking, statistical analysis, double data checking, and manuscript writing., Tropical Medicine and Health, 47(1), art.no.46; 2019