Comparative study of the antidiabetic potential of Paederia foetida twig extracts and compounds from two different locations in Malaysia

Context: Paederia foetida L. (Rubiaceae) is an edible plant distributed in Asian countries including Malaysia. Fresh leaves have been traditionally used as a remedy for indigestion and diarrhea. Several phytochemical studies of the leaves have been documented, but there are few reports on twigs. Objective: This study investigates the enzyme inhibition of P. foetida twig extracts and compound isolated from them. In addition, in silico molecular docking of scopoletin was investigated. Materials and methods: Plants were obtained from two locations in Malaysia, Johor (PFJ) and Pahang (PFP). Hexane, chloroform and methanol extracts along with isolated compound (scopoletin) were evaluated for their enzyme inhibition activities (10,000-0.000016 µg/mL). The separation and identification of bio-active compounds were carried out using column chromatography and spectroscopic techniques, respectively. In silico molecular docking of scopoletin with receptors (α-amylase and α-glucosidase) was carried out using AutoDock 4.2. Results: The IC50 values of α-amylase and α-glucosidase inhibition activity of PFJ chloroform extract were 9.60 and 245.6 µg/mL, respectively. PFP chloroform extract exhibited α-amylase and α-glucosidase inhibition activity (IC50 = 14.83 and 257.2 µg/mL, respectively). The α-amylase and α-glucosidase inhibitory activity of scopoletin from both locations had IC50 values of 0.052 and 0.057 µM, respectively. Discussion and conclusions: Separation of PFJ chloroform extract afforded scopoletin (1), stigmasterol (2) and γ-sitosterol (3) and the PFP chloroform extract yielded (1), (2), (3) and ergost-5-en-3-ol (4). Scopoletin was isolated from this species for the first time. In silico calculations gave a binding energy between scopoletin and α-amylase of -6.03 kcal/mol

Look, the World is Watching How We Treat Migrants! The Making of the Anti-Trafficking Legislation during the Ma Administration

Employing the spiral model, this research analyses how anti-human trafficking legislation was promulgated during the Ma Ying-jeou (Ma Yingjiu) presidency. This research found that the gov- ernment of Taiwan was just as accountable for the violation of mi- grants’ human rights as the exploitive placement agencies and abusive employers. This research argues that, given its reliance on the United States for political and security support, Taiwan has made great ef- forts to improve its human rights records and meet US standards for protecting human rights. The reform was a result of multilevel inputs, including US pressure and collaboration between transnational and domestic advocacy groups. A major contribution of this research is to challenge the belief that human rights protection is intrinsic to dem- ocracy. In the same light, this research also cautions against Taiwan’s subscription to US norms since the reform was achieved at the cost of stereotyping trafficking victimhood, legitimising state surveillance, and further marginalising sex workers

Draft genome sequence of the mulberry tree Morus notabilis

Human utilization of the mulberry–silkworm interaction started at least 5,000 years ago and greatly influenced world history through the Silk Road. Complementing the silkworm genome sequence, here we describe the genome of a mulberry species Morus notabilis. In the 330-Mb genome assembly, we identify 128 Mb of repetitive sequences and 29,338 genes, 60.8% of which are supported by transcriptome sequencing. Mulberry gene sequences appear to evolve ~3 times faster than other Rosales, perhaps facilitating the species’ spread worldwide. The mulberry tree is among a few eudicots but several Rosales that have not preserved genome duplications in more than 100 million years; however, a neopolyploid series found in the mulberry tree and several others suggest that new duplications may confer benefits. Five predicted mulberry miRNAs are found in the haemolymph and silk glands of the silkworm, suggesting interactions at molecular levels in the plant–herbivore relationship. The identification and analyses of mulberry genes involved in diversifying selection, resistance and protease inhibitor expressed in the laticifers will accelerate the improvement of mulberry plants

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Phytochemical studies and in vitro, in vivo and in silico antidiabetic activities of Paederia foetida L. extract

Paederia foetida L. (Rubiaceae) is an edible plant distributed in Asian countries including Malaysia. Fresh leaves have been traditionally used to treat various diseases, including diabetes and as a remedy for indigestion and diarrhea. The plant has reported as antioxidant and antidiabetic properties. The plant is known as rich source of alkaloids, flavonoids, phenols, terpenoids etc. However, the bioactive compounds and the mechanisms of their beneficial effects have remained largely unknown particularly on the twig part of the plant. Therefore, the study covered the investigation of the enzyme inhibition ( -amylase, -glucosidase, and dipeptidyl peptidase-4) of Paederia foetida twig extracts by in vitro assays, the identification of the phytoconstituents of Paederia foetida twigs, evaluation of the antidiabetic activity of Paederia foetida using high fat diet-low dose streptozotocin-induced Sprague Dawley rats model, and performance of in silico molecular docking of identified bioactive compounds. The chloroform extract showed the lowest in vitro -amylase (9.60 μg/mL), -glucosidase (245.6 μg/mL), and dipeptidyl peptidase-4 (DPP-4) (67.40%) inhibition activities compared to other extracts. -amylase -glucosidase inhibitory activity of the isolated compound, scopoletin had IC50 values of 0.052 and 0.057 mM, respectively. The chloroform extract also showed the highest total phenolic content among all the extracts. For the identification of antidiabetic compounds or enzyme inhibitors, assay guided isolation and metabolomics techniques were applied. Assay guided isolation technique revealed the chloroform extract as the most active extract and further purification afforded scopoletin as a bioactive antidiabetic compound. Meanwhile loading column scatter plot of orthogonal partial least square (OPLS) model in Gas Chromatography-Mass Spectrometry (GC-MS) metabolomics revealed the presence of 12 antidiabetic compounds, namely, dl- -tocopherol, n-hexadecanoic acid, 2-hexyl-1-decanol, stigmastanol, 2-nonadecanone, cholest-8(14)-en-3-ol,4,4-dimethyl-,(3 ,5 )-, stigmast- 4-en-3-one, stigmasterol, 1-ethyl-1-tetradecyloxy-1-silacyclohexane, -sitosterol, stigmast-7-en-3-ol, (3 ,5 ,24S)-, and -monostearin. For proton Nuclear Magnetic Resonance (1H-NMR) metabolomics, the chloroform extract showed the presence of 13 antidiabetic compounds, campesterol, - -terpineol, lupeol, epifriedelinol, embelin, scopoletin, rutin, apigenin, geniposide, and linarin. The standardization of the chloroform extract was carried out to identify the exact amount of the biomarker derived from the plant. The qNMR is a powerful analytical tool for the rapid and accurate determination of bioactive ingredients in herbal preparation. The validated qNMR method showed a good linearity (r2 = 0.9999), limit of detection (0.009 mg/mL), and quantification (0.029 mg/mL), together with high stability (relative standard deviation = 0.022%), high precision (RSD < 1%), and good recovery (94.08%- 108.45%). The P. foetida chloroform extract showed 7.34% scopoletin content, while the other extracts did not show any scopoletin content. The standardized extract was further evaluated for in vivo antidiabetic study at doses of 50 (Group 4) and 100 (Group 5) mg/kg and compared with 300 mg/kg metformin (Group 6). The in vivo results indicated that P. foetida extract of 50 mg/kg displayed the management of metabolic disorders of diabetic rats toward the normal state. The normal and obese rats displayed normal range of blood glucose levels while higher levels in diabetic rats. Groups 4, 5, and 6 showed significant decrement of blood glucose levels compared to diabetic rats (Group 3). There was 27.19% reduction of blood glucose level in Group 4 followed by 23.14% in Group 6 and then 16.79% in Group 5. Group 4 improved lipid profile, renal, and liver function as compared to Group 5 and 6. Group 4 showed reduction in the serum total cholesterol, triglycerides, low-density lipoproteins, uric acid, AST, and ALP and increase in high-density lipoprotein and total protein. Besides that, Group 4 exhibited good antioxidant activities in catalase (25.96 U/mg protein) and glutathione peroxidase (17.62 nmol/mg protein) analysis in the liver tissues, respectively. Group 4 also able to reduce the oxidative stress in protein carbonyl content and receptor for advanced glycation end-product markers. Molecular docking study was attempted to elucidate the mechanisms by which the active compounds could induce antidiabetic activities in - amylase, -glucosidase, and DPP-4. In silico calculations gave binding energy between scopoletin -amylase, -glucosidase, and DPP-4 of -6.03, -2.92, and -6.1 kcal/mol, respectively. A total of two hydrogen bonds (Glu171 and Gly139) were observed in scopoletin- -amylase complex along with one hydrophobic interaction (Ala169). The scopoletin- -glucosidase complex showed two hydrogen bonding (Arg450 and Gln439) and one hydrophobic interaction (Tyr41). Besides that, one hydrogen atom in scopoletin showed a carbon-hydrogen bond to Ser360 in the DPP-4 enzyme. In conclusion, P. foetida exhibited enzyme inhibition in vitro and improved glucose and biochemical parameters in diabetic rats. This study suggested the potential of P. foetida as health promoting agent for Type 2 Diabetes Mellitus

Identification of antidiabetic metabolites from Paederia foetida L. twigs by gas chromatography-mass spectrometry-based metabolomics and molecular docking study

Paederia foetida L. (Rubiaceae) is a climber which is widely distributed in Asian countries including Malaysia. The plant is traditionally used to treat various diseases including diabetes. This study is to evaluate the enzymatic inhibition activity of Paederia foetida twigs extracts and to identify the metabolites responsible for the bioactivity by gas chromatography-mass spectrometry (GC-MS) metabolomics profiling. Three different twig extracts, namely, hexane (PFH), chloroform (PFC), and methanol (PFM), were submerged for their α-amylase and α-glucosidase inhibition potential in 5 replicates for each. Results obtained from the loading column scatter plot of orthogonal partial least square (OPLS) model revealed the presence of 12 bioactive compounds, namely, dl-α-tocopherol, n-hexadecanoic acid, 2-hexyl-1-decanol, stigmastanol, 2-nonadecanone, cholest-8(14)-en-3-ol, 4,4-dimethyl-, (3β,5α)-, stigmast-4-en-3-one, stigmasterol, 1-ethyl-1-tetradecyloxy-1-silacyclohexane, ɣ-sitosterol, stigmast-7-en-3-ol, (3β,5α,24S)-, and α-monostearin. In silico molecular docking was carried out using the crystal structure α-amylase (PDB ID: 4W93) and α-glucosidase (PDB ID: 3WY1). α-Amylase-n-hexadecanoic acid exhibited the lowest binding energy of -2.28 kcal/mol with two hydrogen bonds residue, namely, LYS178 and TYR174, along with hydrophobic interactions involving PRO140, TRP134, SER132, ASP135, and LYS172. The binding interactions of α-glucosidase-n-hexadecanoic acid complex ligand also showed the lowest binding energy among 5 major compounds with the energy value of -4.04 kcal/mol. The complex consists of one hydrogen bond interacting residue, ARG437, and hydrophobic interactions with ALA444, ASP141, GLN438, GLU432, GLY374, LEU373, LEU433, LYS352, PRO347, THR445, HIS348, and PRO351. The study provides informative data on the potential antidiabetic inhibitors identified in Paederia foetida twigs, indicating the plant has the therapeutic effect properties to manage diabetes

Antidiabetic effect of Melicope glabra (Blume) T.G. Hartley (Rutaceae) in high-fat diet/streptozotocin-induced diabetic rats and its bioactive components

Melicope glabra (Blume) T.G. Hartley is a plant of Rutaceae family. The present study aimed to evaluate the in vivo hypoglycemic effect of M. glabra leaves extract on diabetic rats and identify its bioactive components. The induc-tion of diabetes in Sprague-Dawley rats was done by a combination of high-fat diet and low-dose streptozotocin injection. The M. glabra extracts and standard sitagliptin were orally administered once daily to the diabetic rats for 28 days. The diabetic rats showed drastic weight loss, hyperglycemia, poor glucose tolerance, hyperlipidemia, and disturbances in the liver and kidney functions. However, oral administration of M. glabra extracts to the dia-betic rats significantly lowered the DPP-4 level and increased glucagon-like peptide-1 (GLP-1) level. Scopoletin, pachypodol, and stigmasterol were revealed as the active DPP-4 and α-amylase inhibitors. This study revealed novel findings which suggest the potential of M. glabra as alternative antidiabetic treatment and source of anti-diabetic agent