A novel water-soluble polysaccharide named PEPW80-1, with a molecular mass of 4.7 kDa, was isolated from the pulp tissues of Phyllanthus emblica, and purified by sephadex G-100 column and sephacryl S-300 HR chromatography. The structural features of PEPW80-1 were investigated by a combination of acid hydrolysis, periodate oxidation-Smith degradation, methylation analysis, gas chromatography-mass spectrometry, scanning electron microscope, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The results showed that PEPW80-1 had a specific optical rotation of [α]25/D = +113° (c = 0.5 mg/mL) and its backbone composed of (1,3)-linked-β-L-rhamnose and (1,3,6)-linkage-β-D-galactose, with two branch chains of (1,4)-linked-α-D-galactose and (1,6)-linked-β-D-galactose and terminated with 1-α-L-arabinose. The antioxidant assays showed that PEPW80-1 possess 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity and hydroxyl radical-scavenging activity, enhancing reductive power. The results of immunomodulatory assays in vitro showed that PEPW80-1 could promote the proliferation of mouse splenocytes. Those proposed that PEPW80-1 might be developed as a potential value-added product with the activities of immunomodulator and free-radical inhibitors.
Clove oil is used in fish anesthesia and expected to have a mechanism via glutamic receptor. The present study explores the activities of clove oil and its major compound, eugenol, in comparison with L-glutamic acid on glutamic receptor of silkworm muscle and fish anesthesia. It was found that clove oil and eugenol had similar effects to L-glutamic acid on inhibition of silkworm muscle contraction after treated with D-glutamic acid and kainic acid. Anesthetic activity of the test samples was investigated in goldfish. The results demonstrated that L-glutamic acid at 20 and 40 mM could induce the fish to stage 3 of anesthesia that the fish exhibited total loss of equilibrium and muscle tone, whereas clove oil and eugenol at 60 ppm could induce the fish to stage 4 of anesthesia that the reflex activity of the fish was lost. These results suggest that clove oil and eugenol have similar functional activities and mechanism to L-glutamic acid on muscle contraction and fish anesthesia.
In the present study, the fractionated extracts of Sesbania grandiflora bark were prepared and evaluated for their biological activities. The ethyl acetate fractionate (EAF) showed high antioxidant activity along with free radical scavenging and reducing mechanisms. The free radical scavenging antioxidant activity of EAF was 69.3 ± 3.6% where its Trolox equivalent antioxidant capacity was 13.6 ± 0.7 mM/mg. EAF exhibited the reducing power equivalent to ferrous sulfate at 152 ± 2 mM/mg and equivalent to gallic acid at 1.05 ± 0.01 mM/mg. In addition, EAF presented high potential on inhibition of bacterial growth with the minimum bactericidal concentration less than 1 mg/mL. Further isolation of EAF using normal-phase open column of silica gel 60, showed that the fractions eluted with the mixture of chloroform and methanol at the ratios of 4:1, 3:2, and 2:3 possessed antibacterial activity. The recovery activity of total different active fractions was 5% EAF, 20 times less than that of EAF. The chromatogram of EAF from a high-performance liquid chromatography was compared with caffeic acid, catechin, coumaric acid, ellagic acid, gallic acid, quercetin, syringin, naringic acid, trans-cinnamic acid, and vanilic acid. The result demonstrated that one major compound of EAF was gallic acid. These results suggest that the fractionated extracts of S. grandiflora bark contained antioxidant and antibacterial activities.
High-level vancomycin resistance among Staphylococcus aureus poses a grave threat to global health as the treatment options for this pathogen are very limited. A detailed evaluation of the genetic background of vancomycin-resistant S. aureus (VRSA) is expected to facilitate the understanding of its origin and pathogenicity. In this study, we performed the genetic analysis of the clinical VRSA isolates and identified the genetic basis of resistance to multiple antibiotics among these strains, based on the available draft genome sequences. In addition, we generated the draft genome of the strain VRS3b, which was considered to be same as VRS3a based on its isolation from the same patient. We found that strain VRS3b did not harbor the genes responsible for tetracycline and gentamicin, which was further confirmed by the sensitivity towards these antibiotics. Our results suggest that the strains VRS3a and VRS3b are different from the view of antibiotic resistance and highlight the possibility of generation of two distinct VRSA strains from the same patient.
Microsomal aromatase enzymes of humans and rats have been used in antiaromatase assays, but enzyme activity is species-specific. The current study extracted hepatic microsomes of Nile tilapia (Oreochromis niloticus) to investigate and compare the antiaromatase activity of chrysin, quercetin, and quercitrin. This activity was evaluated using a dibenzylfluorescein (DBF) assay. Results revealed that the age and body weight of Nile tilapia affected the yield of extracted microsomes. Extraction of hepatic microsomes of Nile tilapia was most effective when using a reaction medium with a pH of 8.0. A DBF assay using Nile tilapia microsomes revealed significant differences in levels of antiaromatase activity for chrysin, quercetin, and quercitrin. Chrysin was the most potent aromatase inhibitor, with an IC50 of 0.25 mg/mL. In addition, chrysin is an aromatase inhibitor that also inhibits the proliferation of cancer cells. Hepatic microsomes of Nile tilapia can be used to investigate and compare the antiaromatase activity of different compounds.
Human saliva is a potential diagnostic fluid and any alteration in body might be reflected in saliva so that saliva is considered as "mirror of the body". Variations in salivary hormone level, ultra structure, pH, flow rate, buffering capacity and electrolytes level are found during menstrual cycle in regard to ovulation. Thirty healthy volunteers were used for the assessment of physico-chemical changes in saliva. Reproductive cycle was categorized as pre-ovulation phase (5 to 12 days), ovulation phase (13 or 14 days) and post-ovulation phase (15 to 25 days) according to salivary arborization test and hormonal analysis. Estradiol and luteinizing hormone was gradually increased and attained peak at the level of 2.28 ± 0.20 pg/mL and 1.35 ± 0.41 mIU/mL respectively during the ovulation phase. The electrolytes result clearly indicates that the influx of common electrolytes is important for crystallization and help to induce clear ferning pattern in ovulation phase. Sodium (Na) and chloride (Cl) were found to be high during ovulation phase only. Average salivary pH was 7.5, 7.1, and 7.3 during ovulation, pre- and post-ovulation phases respectively. Buffering capacity of saliva was normal during pre- and post- ovulation phases. In contrast, in ovulation phase the buffer capacity was slightly higher. At the first time, the scanning electron microscopy (SEM) studies revealed the ultra structure difference of saliva during menstrual cycle. During ovulation phase a compact network-shaped mesh was appeared; such structure was not appeared in pre- and post ovulation phases. Additionally, we observed the saliva is arrayed as a fine mosaic-like structure during ovulation. Based on physico-chemical properties and hormonal levels may lead to develop a detection kit/sensor for detecting the ovulation phase in human.
Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models. This study evaluates ulcer index, hexosamine content, microvascular permeability, and gastric content in three acute stress models (cold-restraint, restraint, and water immersion restraint). Macroscopic pictures of the ulcerogenic stomach explain that in contrast to other models, cold-restraint stress (CRS) exposure produced marked ulcers on the fundic area of the stomach. Results of the present study depicted that each stress model significantly increased ulcer index, microvascular permeability and decreased hexosamine level, however, the maximum in the case of CRS-exposed rats. Total acidity and pH of the gastric content remains unchanged in all the stress models. On the contrary, the gastric volume significantly decreased only in case of CRS, while unchanged in other stress models. The overall results revealed that the CRS resembles the pathophysiology of SRMD closely. It is the best and feasible model among all the models to evaluate drugs for the treatment of SRMD.
Artepillin C (ARC) and caffeic acid (CA) are among the major anti-cancer ingredients of propolis, and block the oncogenic/melanogenic/ageing kinase PAK1. However, mainly due to their COOH moiety, cell-permeability of these herbal compounds is rather limited. Thus, in this study, in an attempt to increase their cell-permeability without any significant loss of their water-solubility, we have esterized both ARC and CA with the water-soluble 1,2,3-triazolyl alcohol through Click Chemistry. We found that this esterization boosts the anti-cancer activity of ARC and CA by 100 and over 400 folds, respectively, against the PAK-dependent growth of A549 lung cells, but show no effect on the PAK1-independent growth of B16F10 melanoma cells. Confirming this "selective" toxicity, these esters are still capable of blocking the kinase PAK1 strongly in cell culture (with IC50 around 5 µM), and the anti-PAK1 activity of 15A (ARC ester) and 15C (CA ester) appears to be 30-fold and 140-fold higher than ARC and CA, respectively. The 15A and 15C are 8-fold and 70-fold more cell-permeable (through the multi-drug resistant cell line EMT6) than ARC and CA, respectively. These data altogether suggest that both 15A and 15C would be far more useful than propolis for the treatment of a wide variety of PAK1-dependent diseases/disorders such as cancers, Alzheimer's diseases (AD), hypertension, diabetes (type 2), and hyper-pigmentation.
A sulfated saponin called "Frondoside A" (FRA) from sea cucumber and ingredients from Okinawa propolis (OP) have been previously shown to suppress the PAK1-dependent growth of A549 lung cancer as well as pancreatic cancer cells. However, the precise molecular mechanism underlying their anti-cancer action still remains to be clarified. In this study, for the first time, we found that both FRA and OP directly inhibit PAK1 in vitro in a selective manner (far more effectively than two other oncogenic kinases, LIMK and AKT). Furthermore, at least two major anti-cancer ingredients of OP, nymphaeols A and C, also directly inhibit PAK1 in vitro in a selective manner. To the best of our knowledge, FRA is the first marine compound that selectively inhibits PAK1. Likewise, these nymphaeols are the first propolis ingredients that selectively inhibit PAK1.
Levetiracetam and topiramate are newer anticonvulsants, which is why international data on overdoses of these drugs are lacking. Only a few mild adverse reactions have been noted. These anticonvulsants have been the drug of choice for neurologists. Despite their wide usage, there is a dearth of literature on symptoms and signs of their toxicity. Presented here is the case of a 21-year-old female who overdosed twice on levetiracetam and topiramate. The woman was admitted and discharged after the first overdose. Ten days later, she took multiple tablets of both drugs and was seen again. Amazingly, the woman went home after the incident with no complications at all.
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