High catechin concentrations detected in Withania somnifera (ashwagandha) by high performance liquid chromatography analysis

<p>Abstract</p> <p>Background</p> <p><it>Withania somnifera </it>is an important medicinal plant traditionally used in the treatment of many diseases. The present study was carried out to characterize the phenolic acids, flavonoids and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activities in methanolic extracts of <it>W. somnifera </it>fruits, roots and leaves (WSFEt, WSREt and WSLEt).</p> <p>Methods</p> <p>WSFEt, WSREt and WSLEt was prepared by using 80% aqueous methanol and total polyphenols, flavonoids as well as DPPH radical scavenging activities were determined by spectrophotometric methods and phenolic acid profiles were determined by HPLC methods.</p> <p>Results</p> <p>High concentrations of both phenolics and flavonoids were detected in all parts of the plant with the former ranging between 17.80 ± 5.80 and 32.58 ± 3.16 mg/g (dry weight) and the latter ranging between 15.49 ± 1.02 and 31.58 ± 5.07 mg/g. All of the three different plant parts showed strong DPPH radical scavenging activities (59.16 ± 1.20 to 91.84 ± 0.38%). Eight polyphenols (gallic, syringic, benzoic, p-coumaric and vanillic acids as well as catechin, kaempferol and naringenin) have been identified by HPLC in parts of the plant as well. Among all the polyphenols, catechin was detected in the highest concentration (13.01 ± 8.93 to 30.61 ± 11.41 mg/g).</p> <p>Conclusion</p> <p>The results indicating that <it>W. somnifera </it>is a plant with strong therapeutic properties thus further supporting its traditional claims. All major parts of <it>W. somnifera </it>such as the roots, fruits and leaves provide potential benefits for human health because of its high content of polyphenols and antioxidant activities with the leaves containing the highest amounts of polyphenols specially catechin with strong antioxidant properties.</p

Protein-based identification of quantitative trait loci associated with malignant transformation in two HER2+ cellular models of breast cancer

Background A contemporary view of the cancer genome reveals extensive rearrangement compared to normal cells. Yet how these genetic alterations translate into specific proteomic changes that underpin acquiring the hallmarks of cancer remains unresolved. The objectives of this study were to quantify alterations in protein expression in two HER2+ cellular models of breast cancer and to infer differentially regulated signaling pathways in these models associated with the hallmarks of cancer. Results A proteomic workflow was used to identify proteins in two HER2 positive tumorigenic cell lines (BT474 and SKBR3) that were differentially expressed relative to a normal human mammary epithelial cell line (184A1). A total of 64 (BT474-184A1) and 69 (SKBR3-184A1) proteins were uniquely identified that were differentially expressed by at least 1.5-fold. Pathway inference tools were used to interpret these proteins in terms of functionally enriched pathways in the tumor cell lines. We observed protein ubiquitination and apoptosis signaling pathways were both enriched in the two breast cancer models while IGF signaling and cell motility pathways were enriched in BT474 and amino acid metabolism were enriched in the SKBR3 cell line. Conclusion While protein ubiquitination and apoptosis signaling pathways were common to both the cell lines, the observed patterns of protein expression suggest that the evasion of apoptosis in each tumorigenic cell line occurs via different mechanisms. Evidently, apoptosis is regulated in BT474 via down regulation of Bid and in SKBR3 via up regulation of Calpain-11 as compared to 184A1

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

<p>Abstract</p> <p>Background</p> <p>Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.</p> <p>Discussion</p> <p>In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.</p> <p>As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.</p> <p>Summary</p> <p>Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.</p

No evidence for the effectiveness of bracing in patients with thoracolumbar fractures

Background and purpose The use of braces is widespread in patients with thoracolumbar fractures. The effectiveness of bracing, however, is controversial. We sought evidence for the effect of bracing in patients with traumatic thoracolumbar fractures based on outcome and length of hospital stay (LOS). Furthermore, we evaluated the incidence of complications of bracing. Methods An electronic search strategy with extensive MeSH headings was used in various databases to identify studies that compared bracing and non-bracing therapies. Two reviewers independently selected systematic reviews, randomized controlled trials (RCTs), controlled clinical trials, and observational studies, and both assessed the methodological quality and extracted the data. Results No systematic reviews or RCTs were found. 7 retrospective studies were included. None of these studies showed an effect of bracing. Because of poor methodological quality, no best-evidence synthesis could be performed. One observational study was selected in which a complication of bracing was reported. Interpretation In the present literature, there is no evidence for the effectiveness of bracing in patients with traumatic thoracolumbar fractures. The lack of high-quality studies prevents relevant conclusions from being draw

Assessment of protein-protein interfaces in cryo-EM derived assemblies

Structures of macromolecular assemblies derived from cryo-EM maps often contain errors that become more abundant with decreasing resolution. Despite efforts in the cryo-EM community to develop metrics for map and atomistic model validation, thus far, no specific scoring metrics have been applied systematically to assess the interface between the assembly subunits. Here, we comprehensively assessed protein–protein interfaces in macromolecular assemblies derived by cryo-EM. To this end, we developed Protein Interface-score (PI-score), a density-independent machine learning-based metric, trained using the features of protein–protein interfaces in crystal structures. We evaluated 5873 interfaces in 1053 PDB-deposited cryo-EM models (including SARS-CoV-2 complexes), as well as the models submitted to CASP13 cryo-EM targets and the EM model challenge. We further inspected the interfaces associated with low-scores and found that some of those, especially in intermediate-to-low resolution (worse than 4 Å) structures, were not captured by density-based assessment scores. A combined score incorporating PI-score and fit-to-density score showed discriminatory power, allowing our method to provide a powerful complementary assessment tool for the ever-increasing number of complexes solved by cryo-EM

Wild species of vaccinium composition, nutritional value and utilization

There are still, in many parts of the globe, some edible fruit collects from the wild for human feeding and other uses. These fruits are utilised either in their raw nature or after some form of processing. One of these wild fruits are Vaccinium species such as Vaccinium myrtoides (Blume) Miq., Vaccinium cylindraceum, Vaccinium padifolium, Vaccinium corymbosum, Vaccinium myrtillus and others from the plant family Ericaceae. The term wild infers non-cultivated plants found in plantation felids or the forest. The species Vaccinium myrtoides and the others are small trees (shrubs) that are well known in Southeast Asian countries such as Philippines, Indonesia and other neighbouring islands. The plants classified as wild growing shrubs. However, the locals have made it be fully utilized in some areas as the wood that are used in grafting utensils and cutleries, or as fuel and fruits. The small-sized berry-like fruits with an average diameter of about 4–5 mm turn black when ripe. They have a delicious flavour that makes it edible and used in the making of other delicacies such as tart and pies to add flavour and as preservatives as well. A few published researches were done on Vaccinium myrtoides showing that it is still used in folkloric medicine. Leaves and fruits extracts showed strong antioxidant activity when tested in-vitro using DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging activity as part of a preliminary phytochemical screening for V. myrtoides. The study revealed that the antioxidant activity is due to the presence of flavonoids and other phenolic compounds in the plant leaves and fruit extracts