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Aim: Hepatocellular carcinoma (HCC) is the world's second leading cause of cancerrelated mortality and the fifth most prevalent cancer overall. Several synthetic and plant-based remedies are in practice to treat diverse liver disorders. Because of their minimal side effects and protective characteristics, plant phenolics have the potential to become alternative therapeutics, replacing currently existing HCC medications. The present study identifies the plant phenolics as having the capacity to inhibit HCC with low side effects and cost efficiency. Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality, despite the proven effectiveness of screening programs for at-risk individuals, the majority of patients have disease progression or tumor characteristics that preclude curative therapies at the time of diagnosis. Acteoside (Verbascoside) is a naturally occurring phenylethanoid glycoside found throughout the plant kingdom. Acteoside is a physiologically active chemical with the number of pharmacological and protective effects against various liver illnesses. Objectives: Currently used HCC medications have a variety of side effects. Plant-based chemicals offer the possibility of treating HCC with minimal side effects. The work is targeted to find the best phytochemical (plant phenolic) lead molecule for future drug development research against Hepatocellular carcinoma. Methods: The targets were selected based on an analysis of relevant literature, and the 3D structures of the selected receptors were obtained in. pdb format from the RCSB-Protein data bank (PDB, http://www.rscb.org/pdb). Based on a review of the literature, sixty plant secondary metabolites, or plant phenolics, were selected. The ligand structures were obtained and downloaded in.sdf format from the NCBI PubChem chemicals database (https://pubchem.ncbi.nlm.nih.gov/). Molecular docking between the receptor and ligands was accomplished using the Molegro Virtual Docker 6.0 (MVD) software. Results: The target RAF1, BRAF chain 1, TIE2 chain 2 FGFR1, FGFR2, AXL, and FGFR4 showed the best binding effectiveness with acteoside compared to their respective positive control. RET chain 1 and BRAF chain 2 acteoside showed prominent binding efficacy after Curcumin, and Epigallocatechingallate, respectively, against positive control. Present findings clearly point towards the potentiality of acteoside in inhibiting various HCC targets. Conclusion: Acteoside may be used as a prominent lead molecule in the future treatment of hepatic cancer with its multifaceted binding efficiencies against various target proteins.

Abstract: Indian Arrowroot (Curcuma angustifolia Roxb) belongs to the Zingiberaceae family is widely distributed in India and some parts of Nepal, Thailand, Bangladesh, Pakistan. It is traditionally used as medicine for treating various diseases and also used as food. Few data are available about its application in pharmacology and therapeutics. Literature search for related contents, keywords such as “Curcuma angustifolia Roxb”, “traditional food”, “ethnomedicine”, “pharmacology”, “phytochemicals”, “pharmacological activities” were used in search engines including pubmed, google scholar, scopus, sciencedirect, and semantic scholar. Secondary metabolites found in Indian Arrowroot include essential oils, alkaloids, flavonoids, terpenoids, phytosterols, terpenes, phenols, and others. Pharmacological activities such as antioxidant, anti-inflammatory, anti-proliferative, anti-ulcerogenic, hepatoprotective, and anti-cancerous activities have been shown by Indian Arrowroot (Curcuma angustifolia Roxb). The presence of nutritional value and pharmaceutical potential gained demand in the various food production industries and pharmacology research. It may play a vital role for future studies of Curcuma angustifolia Roxb as ethnomedicine and further exploitation in pharmacological studies.

Our health-care system would be incomplete without the use of medicinal herbs. In the days before modern medicine, several communities created medical knowledge systems known as “traditional medicine,” “indigenous medicine,” or “folk medicine.” The medicinal properties of plants and plant-based products are widely accepted. There are a variety of medical approaches available across the world, including allopathic, homoeopathic, Ayurvedic, and Chinese. The developed communities each have their own Materia Medica, which compiles thorough data on many plants used as medicines. According to current estimations from the field of botany, there are somewhere between 2,50,000 and 3,50,000 distinct plant species in existence. It is estimated that 35,000 unique species are used to cure a wide range of ailments in diverse places throughout the world. Based on general popularity among all ages, phytopharmaceuticals are an integral part of worldwide business and the global economy. According to a globe news wire study, the global herbal medicine market is estimated to be 550 billion dollars by 2030, up from 83 billion dollars in 2019. China and India lead the global herb market. China exports 120,000 tonnes of herbal remedies annually, followed by India with 32,000 tonnes. Europe is the world’s largest importer of medicinal plants (MP), taking in over 400,000 tonnes annually to fulfill local demand. In this review, we have discussed about the MP and their economic importance in global market.

It is known that molecular changes in apoptotic genes due to mutation may cause disruption of apoptotic pathway resulting in an abrupt increase in cell proliferation. Therefore, it is of interest to identify compounds that could potentially replenish the changes in the apoptotic pathway, resulted from mutation. The gene network analysis using the Network Analyzer Plugin of Cytoscape (3.5.1) shows CFLAR and TRAF2 as influential genes in the apoptotic pathway. Mutation in these genes brings loss in apoptotic property of a cell and thus increases the cell proliferating activity. Thus, data on the molecular docking analysis of four natural compounds from Ottelia alismoides (L.) Pers with the two target proteins were reported. Flupenthixol and desmethylastemizole was found to be two efficient ligand molecules based on ligand-target interaction. In stereochemical quality assessment, the Ramachandran plot analysis of receptors indicates the better stereochemical characteristics for receptor-ligand interaction.

The North-eastern parts of India have immense therapeutic floras, Ottelia alismoides is an aquatic plant that has been in use for a long time in traditional medicine for treating diseases like cancer, tuberculosis, diabetes, febrifuge, hemorrhoids, and rubefacient. In lung and skin carcinoma cells with a high rate of proliferation and metastasis including drug resistance and non-specific target activity, generates important challenges towards their treatment strategy. Thus, finding novel therapeutic targets to treat lung and skin cancer progression is essential to enhance the patients' survival with treatment.The purpose of this study was to evaluate the apoptotic potential of acetone extract of O. alismoides (L.) Pers. (OA-AC) and to identify the compounds responsible for this effect, HRLC-MS-QTOF analysis of the extract has been undertaken along with in-silico molecular docking analysis of the identified compounds.A549 and A431 cells were treated with acetone extract of O. alismoides (OA-AC) at 24 h and 48 h exposure and cell cycle phase distribution was evaluated and also apoptosis induction activity was evaluated by OA-EtBr staining and Mitochondrial outer membrane potential assay. Western blotting was performed for the evaluation of apoptotic protein expression. At last, the HR-LCMS of OA-AC was analyzed to identify the compounds responsible for the apoptotic activity of the extract.The cell cycle phase distribution analysis in A549 and A431 cells at 24hrs exposure with 10 μg/mL and 25 μg/mL of OA-AC showed a potent arrest or blockage at the G2/M phase of the cell cycle with reduced expression of cyclin B and p-Cdc2. At 48 h exposure, apoptosis was observed in these cancer cells with elevated expression of Bax, p21 and cleaved caspase 3 and reduced expression of the Bcl2.AO-EtBr staining of these cancer cells reveals that the death induced by OA-AC was apoptotic in nature with depolarization of mitochondrial membrane due to loss or damage of the mitochondrial membrane. The HRLC-MS-QTOF analysis of OA-AC depicted 14 major isolable compounds and molecular docking analysis displayed 4 compounds that might act as an inhibitor of cyclin B for G2/M phase arrest that leads to apoptotic induction in the cells.

Abstract: Deadly disease cancer has many types; among them, lung cancer is responsible for the highest number of cancer mortality. Existing therapies as well as drugs for treating lung cancer are not effective and are often associated with innumerable side effects and toxicities. For these reasons, researchers have been working on developing novel anti-cancer medicines from plants and other natural sources that have a high safety profile. Natural flavonoids are a polyphenolic group of phytochemicals extracted from plants and other plant-derived compounds. Natural flavonoids are gaining popularity due to their unique and priceless medicinal properties, including anticancer properties. Several researchers have already declared that flavonoids possess the ability to treat different cancers, particularly lung cancer. The bioactivity of natural flavonoids is mainly due to their structural diversity. Natural flavonoids fight against lung cancer by regulating redox homeostasis, upregulating apoptosis, pro-apoptotic factors, and survival genes, arresting cell cycle progression, autophagy, reducing cell proliferation and invasiveness, maintaining inflammation response, downregulating anti-apoptotic factors, and targeting lung cancer signaling pathways. Flavonoids can act alone or synergistically with other agents to treat lung cancer. Due to these reasons, it is possible to use natural flavonoids as pharmaceutical leads to prevent and treat lung cancer.

Objectives: The work aims to screen the antioxidative potentials of different crude extracts of the fronds of two medicinally important pteridophytes of Southern Assam, India, namely, Cyclosorus interruptus (Willd.) H. Itô and Pronephrium nudatum (Roxb. ex Griff.) Holttum. Methods: Frond extracts of the pteridophytes were prepared by Soxhlet hot extraction method. Total phenolic content (TPC) and total flavonoid content (TFC) of the hexane, ethyl acetate, acetone, and methanol extracts of the fronds of the plants were done by following standard protocol. In vitro assessment of the antioxidative behavior of the extracts was performed using standard 2,2-diphenyl-1-picrylhydrazyl scavenging assay, reducing power assay, metal chelating assay, hydroxyl, superoxide, and 2,2’- azino-bis (3-ethylbenzothiazoline - 6 – sulfonic acid) radical scavenging methods in different in vitro systems. Results: Preliminary phytochemical analysis implicated the presence of phenolic and flavonoid compounds in all the frond extracts. The methanol extract of the fronds of both the plants showed maximum phenolic and flavonoid contents in comparison to the other extracts, however, that of C. interruptus was found to be higher than P. nudatum. Antioxidative potentials of the said extracts were also found to be impressive and noteworthy. The decreasing order of the antioxidative efficacies of the extracts was found to be same as that of TPC and TFC of the extracts. Conclusion: It is pertinent to comment that the methanol extract of the fronds of both the plants may be treated as a potential source of natural antioxidants.

The major cause of death around the world is cardiovascular disease, while cancer ranks second. Lung cancer stands out as a major cause of concern because it accounts for 12% of all cancer cases and is the leading cause of cancer-related death. Since prehistoric times, humans have relied on plants as a reliable resource for all three of these essentials: food, livestock, and healthcare. When it comes to treating human illness, plants have been relied on extensively. Researchers are becoming increasingly intrigued by the prospect of deciphering plant chemistry. The Alliaceae plant family has yielded many novel phytochemicals. To identify a potent phytocompound against lung cancer from the plant Allium tuberosum Rottler ex Spreng, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were performed. Before that, total phenolic content (TPC), total flavonoid content (TFC), and DDPH free radicals scavenging activity were determined in order to select the best plant extract. Four targets for non-small cell lung cancer (NSCLC) were retrieved in mutated form by literature mining to carry out this work. EGFR and B-Raf were selected as cell proliferating proteins and K-Ras and PI3K were selected as antiapoptotic proteins. Molecular docking was performed against these targets with the 94 phytocompounds present in Allium tuberosum, which were identified by GC-MS and LC-MS. Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling was also conducted with the nine best-screened compounds. Americine, an alkaloid from this plant, showed inhibitory activity against all four selected targets and was bound more strongly than their respective positive controls in docking studies amongst all other phytocompounds. The ADMET study also confirmed the drug-like candidature of the compound. This study reveals the alternative therapeutic potential of americine against NSCLC by promoting apoptosis and inhibiting cell proliferation.

Resting-state fMRI (rsfMRI) was firstly characterized by Biswal et al [1] in the year 1995 and since then it is used for studying patients with various neurosurgical, neurologic, and other brain-related disorders. Various statistical methods are used to analyze the resting-state functional magnetic resonance imaging connectivity. This paper attempts to explore more on the learning of resting-state functional magnetic resonance imaging connectivity. This study will help to understand the usage of rsfMRI to evaluate functional connectivity in the human brain and its usage for surgical decision-making for drug-resistant epilepsy. This paper explains the significance of such connectivity analysis, the methods available for it, and the shortcomings associated with the data.

Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents.

Ethnomedicinal plants and herbal formulations are the most common ingredients for the development of a potential herbal medicine (HM). Therapies leading to the remedy of various ailments using herbal medicine have been in practice from the prehistoric ages. In India, approximately 65–70% of the rural population depends on herbal medicine in the form of Ayurveda, Unani, Siddha, and other indigenous ethnic systems. Globally, the margin of herbal medicine utilization is quite fascinating due to the side effects of using their synthetic counterparts for an extended period. Over time, the necessity of using HM became integral, and the drug development progressed accordingly. In 2016, the value of global HM market was USD 71.19 billion which was USD 63.05 billion in 2014. Witnessing that fact at global HM market, the level is expected to grow significantly in the future. This chapter aims to consolidate the discovered herbal origin drug leads and their possible role in the betterment of the herbal medicine system.

Intellectual property right (IPR), an exclusive privilege for intangible human creation, incorporates elusive manifestations of the human acumen and envelops copyrights, patent, and trademarks. It incorporates different sorts of rights, for example, exchange insider facts, publicity rights, moral rights, and rights against unjustifiable rivalry. Both in developed and developing countries, herbal-based drugs are now gaining importance in curing vivid physiological anomalies and in turn enriching their commercial values. These increasing demands of traditional plant-based medicines are due to their affordability and availability. Traditional medicine generally includes natural assets and the information of local and indigenous people groups as well as healers in regard to their therapeutic utility. Subsequently, it is interlinked with biodiversity preservation and indigenous people groups’ rights over their insight and assets. So, for this situation, there is a constant need for improving the safety of both pharmaceutical and conventional frameworks. Again, there is a probability of stealing of newly designed or some novel developed medication derived from natural products. To ensure safety of research, it is mandatory to protect the discovered outcome or product by any means involving law. Such protecting law includes patent or with trade secret. In this chapter, we will discuss the importance of intellectual property rights (IPR) and patent in the field of natural product research.

Plant-based natural components have always been an important source of food and beverages. Traditional beverages are either directly derived from a single plant or by mingling several components of more than one plant. Beverages of plant origin are also known to be good healers of many ailments. North-east India has diverse ethnic communities which have very rich traditional and cultural practices of herbal products; traditional practice of beverages is also a part of their living. Extract of fruits, vegetables, food grains, and other plant parts is used in the preparation of beverages either in raw form or through fermentation. They have their own traditional method of fermenting food materials to get the desired beverages. In modern scientific era, use of their traditional knowledge in beverage industry could bring a revolution in terms of production as well as in maintaining proper natural nutrient constituents of the beverages.

Fungal endophytes are epitomes of various secondary metabolites and natural products, which have a place in the medical and industrial arenas. They comprise components of plant microecosystems that dwell asymptomatically and symbiotically within plant tissue systems. Certain contemporaneous endophytes and their specific hosts have established a unique correlation that can expressively control plant metabolites and affect the physicochemical properties of medicinal-plant-based crude drugs. Currently, shifting lifestyles have led to a rise in maladies like pulmonary disease, asthma, cardiovascular diseases, and cancer. Though several new medicines have been introduced to the market, the development of resistance to these drugs has become increasingly evident, especially in patients suffering from chronic disease. Synthetic drug therapy has proven to be uncertain, so there is an overall need to develop new protective agents from microorganisms that are highly effective with minimal side effects. Natural products thus have always been a choice for the isolation of novel bioactive molecules for diverse therapeutic applications. It has been determined that nearly 20, 00,000 natural products are of microbial origin. This chapter will thus provide an insight into the novel aspects of some natural products of fungal endophytic origin that may have significant therapeutic potential in disease control and eventually facilitate product discovery with a focus on understanding the interface between endophytic fungi and therapeutic plants. Such an understanding can lead to a more widespread use of superior plant-based drugs in the near future.

Ethnopharmacological relevance Being one of the most common types of life threatening diseases in Southern Assam, India, the digestive system disorders (DSD) have gained much attention in recent decades. Traditional beliefs and inadequate income of mass population result in the use of alternative phytotherapies to treat the diseases. Aim of the study The present paper documents the medicinal knowledge and utilization of plants for treatment of digestive system disorders in Southern Assam, India by Disease Consensus Index (DCI). It also determines the most suitable plant species used to treat digestive system disorders in the study area. Materials and methods The study was based on ethnomedicinal field survey covering a period of 1 year from 2014–2015. The ethnomedicinal information was collected by using semi-structured questionnaires from different traditional Bengali people having knowledge on medicinal plants. Collected data were analyzed by calculating DCI. Results During the survey, 29 informants were interviewed and a total of 49 plants under 46 genera belonging to 33 families were listed. Data analysis revealed that Litsea glutinosa, Momordica charantia, Andrographis paniculata, Lawsonia inermis, Cleome viscosa, Psidium guajava, Ageratum conyzoides, Cuscuta reflexa, Cynodon dactylon and Carica papaya are the most prominent plants among the people of Southern Assam for treating DSD. Conclusion This explorative survey emphasizes the need to preserve and document the traditional healing practices for managing DSD inviting for more imminent scientific research on the plants to determine their efficacy as well as safety. With the help of statistical analysis (DCI), we propose 10 priority plants for DSD in present work. Systematic pharmacological study with these plants may contribute significant result.

Biosurfactant is the exudates of microbial metabolism and also familiar as surface-active compounds. It has netted its rank in both industrial and environmental portion but in medical science, use of same is still in nascent stage. Important probiotics like lactic acid bacteria, Bacillus spp. make up the vital constituents of human microflora, possesses an enormous antimicrobial, antibiofilm, antitumor and anti-adhesive potential. Structural novelty and diverse properties make biosurfactant as probable candidates for beneficial applications today. To attain anticipated success under this approach it is vital to keep in mind that certain microbes must transport some antimicrobial and surface activity. Surface activity aids in potential association with cell membranes of different organisms. Evident from the published literature that microbial surfactants such as lipopeptide and glycolipid showed to inhibit the transmission of cancerous cells and following apoptosis by rapid cell rupture. In drug discovery, biosurfactants appear with a promising drug delivery mode. In general, biosurfactants have strong bactericidal and fungicidal properties. Anti-adhesiveness of biosurfactant against pathogenic candidates marks them helpful for curing many diseases and also as therapeutic candidates. Structural diversity, their mode of actions and future prospects in medical sciences are the points of discussions under this review.

Diabetes mellitus (DM) is an endocrine disorder affecting more than 100 million people worldwide. It is exemplified by hyperglycemia caused by imperfect functioning of insulin, abnormal insulin secretion or sometimes the combination of both. The long-term persistence of high glucose concentrations in the blood leads to the generation of abnormally high level of free radicals and reactive oxygen species (ROS), change of various oxidative stress biomarker levels, simultaneous decline of antioxidant defense mechanisms and thereby causes a variety of diabetic complications in the body. Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Abnormally increased production of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, enhanced lipid peroxidation, and development of insulin resistance, creating complicacies. Changes in oxidative stress biomarkers and their consequences are discussed in this chapter. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options. Many ethnobotanically important herbal plants possessing antihyperglycemic potential are known to exist in nature. Moreover, a large number of polyherbal formulations (PHFs) derived from these plants are presently being prescribed as medicinal/dietary supplements for the management of DM. It has become very much essential to explore the hidden active principles present in the traditionally used antidiabetic herbal plants in order to standardize the formulations of various herbal drugs for the betterment of both types of DM treatment. This chapter would well indicate about how oxidative stress is involved in the pathogenesis of diabetes and its complications. The experimental validations and biochemical aspects of traditionally used antidiabetic plants in phytotherapy of DM are discussed to understand and elucidate the antidiabetic as well as associated antioxidative potentials.

Methanolic leaf extracts of the plant species Elsholtzia blanda Benth., Elsholtzia communis (Collett & Hemsl) Diels., Polygonum posumbu Buchanam-Hamilton ex D. Don and Zanthoxylum acanthopodium DC. using methanol as a solvent were tested against 10 human pathogenic bacteria for potential antibacterial activity. The study revealed that all extracts show varied degree of antibacterial activity against the tested bacterial pathogens. The antibacterial activity was determined using agar well diffusion method. Methanolic extract of the leaf Zanthoxylum acanthopodium DC. showed antibacterial activity against five bacterial strains from among the ten bacteria tested followed by Polygonum posumbu , Elsholtzia communis and Elsholtzia blanda . Clostridium sporogenes was found to be susceptible to all the plants tested. Minimum inhibitory concentration of the plants against the tested organism ranged between 3.125-12.5 mg/ml. Hence these plants can be used to discover bioactive natural products that may serve as leads in the development of the new pharmaceuticals. Keywords: Antibacterial, human pathogens, methanolic extract, traditional medicine African Journal of Biotechnology , Vol 13(13), 1491-1495

Malaria remains one of the major infectious diseases in the tropical region because of the development of resistance by the causal organism in response to the existing drugs. It motivated intensive research to discover drugs having novel structures and mechanisms from the natural sources. Several compounds isolated from natural sources are found to possess antimalarial properties. Febrifugine is one of such compounds first isolated from Dichroa febrifuga, a plant traditionally used for antimalarial recipe in China and other parts of Asia. This alkaloid has potent antimalarial properties; however, its clinical usage is impeded by presence of adverse effects and toxicity associated. Now, attention has been provided to synthesis of febrifugine analogs having therapeutic potentials with low toxicity to control malaria. In addition to it, potential applications of febrifugine analogs in controlling cancer and fibrotic diseases have been demonstrated. This chapter provides an overview of the febrifugine and its different analogs for their antimalarial and other therapeutic properties with special reference to their structure–activity relationships.

Ethnopharmacological relevance Information about ethnomedicinal plants used by traditional healers in Tripura, India is very much limited. As there is rapid erosion of traditional knowledge in the state, needs has arisen to document the diversity of medicinal plants, their preparation and associated diseases. Aim of the study Attempts have been made to explore the herbal medicines used by the traditional healers belonging to the various communities in North Tripura district of Tripura, India and document the associated traditional knowledge on the utilisation of medicinal plants. Materials and methods The study was based on ethnomedicinal field survey covering a period of 1 year from February 2012 to February 2013. The ethnomedicinal information was collected by using semi-structured questionnaires from different healers and knowledge holders. Collected data were analysed through informant consensus factor, Index of Specialisation and Relative frequency of citation to determine culturally significant plants. Results A total of 75 species of plants under 68 genera belonging to 43 families were collected during the study for the treatment of 15 disease categories. Leaves were the most frequently used plant parts and most of the medicines were prepared in the form of extract and administered orally. FIC values of the present study indicated that there was a high agreement in the use of plants in the treatment of digestive system disorders and respiratory system disorders among the healers. Plants having high ISu are Justicia adhatoda, Pajanelia longifolia, Catharanthus roseus etc. Conclusion The present study highlighted certain species having higher priority indices for further phytochemical investigation. Counselling of traditional health practitioners should be taken into consideration in order to smooth continuation and extension of traditional medical knowledge and practice for ensuring safe and effective therapy.

The ADAMs (A Disintegrin and Metalloprotease Domains) are a family of membrane-anchored proteins that play a role in fertilisation, myoblast fusion and ectodomain shedding of cell surface proteins. Meltrin gamma (ADAM-9) is a widely expressed member of this family and is involved in the shedding of heparin binding epidermal growth factor. Here we report that meltrin gamma can function as a cell adhesion molecule via its disintegrin domain. Using solid-phase binding assays and antibody inhibition experiments, we demonstrate that a murine meltrin gamma-Fc (Mel gamma -Fc) fusion protein binds to the integrin alpha(6)beta(1) on the surface of fibroblast cell lines, HT1080 and Wehi 164 in a specific manner. Since alpha(6)beta(1) is important for the motility of several cell types on laminin, cell migration studies using time-lapse video microscopy were performed. Cells adhering to Mel gamma-Fc displayed a rounded morphology and a marked increase (eight- to tenfold) in their motility compared to that on laminin. Furthermore, the p160 ROCK kinase inhibitor Y-27632 specifically reduced the migration of cells on meltrin gamma but had no effect on migration of cells on laminin, whilst the general tyrosine phoshorylation inhibitor, genistein, inhibited cell migration on both substrates. These results together suggest that meltrin gamma may play a role in regulating the motility of cells by binding to alpha(6)beta(1) integrin and this may be important during a variety of biological and pathological processes.

In many carcinomas, infiltrating macrophages are commonly found closely associated with tumour cells but little is known concerning the nature or significance of adhesion molecules involved in these cellular interactions. Here we demonstrate in primary human breast cancers that sialoadhesin (Sn), a macrophage-restricted adhesion molecule, is frequently expressed on infiltrating cells that often make close contact with breast carcinoma cells. To determine whether Sn could act as a specific receptor for ligands on breast cancer cell lines, binding assays were performed with a recombinant form of the protein fused to the Fc portion of human immunoglobulin G1 (IgG1) (Sn-Fc). Sn-Fc was found to bind specifically and in a sialic acid-dependent manner to the breast cancer cell lines MCF-7, T47.D and BT-20 both in solid- and solution-phase binding assays. To investigate the nature of the sialoglycoproteins recognized by Sn on breast cancer cells, MCF-7 cells were labelled with [6-3H]glucosamine. Following precipitation with Sn-Fc, a major band of approximately 240000 MW was revealed, which was shown in reprecipitation and Western blotting experiments to be the epithelial mucin, MUC1.

Sialoadhesin is a macrophage-restricted transmembrane glycoprotein of 185 kDa that mediates cell–cell interactions through recognition of Neu5Acα2,3Gal in glycoconjugates. The extracellular region of sialoadhesin is composed of seventeen immunoglobulin-like domains, of which the amino-terminal two are highly-related structurally and functionally to the amino-terminal domains of CD22, myelin associated glycoprotein and CD33. These proteins, collectively known as the sialoadhesin family, are able to mediate sialic acid-dependent binding with distinct specificities for both the type of sialic acid and its linkage to subterminal sugars. In this review we discuss our recent studies on sialoadhesin and suggest how this molecule may contribute to a range of macrophage functions, both under normal conditions as well as during inflammatory reactions. Abbreviations: Ig, immunoglobulin; CEA, carcinoembryonic antigen; MAG, myelin associated glycoprotein; SMP Schwann cell myelin protein; mAb, monoclonal antibody; Chinese hamster ovary (CHO); UTR, untranslated region

Sialoadhesin and CD22 are members of a recently characterized family of sialic acid-dependent adhesion molecules belonging to the immunoglobulin superfamily. Sialoadhesin is a macrophage-restricted receptor containing 17 extracellular Ig-like domains which recognizes oligosaccharides terminating in NeuAc alpha 2-3Gal in N- and O-linked glycans. CD22 is a B cell-restricted receptor with seven Ig-like domains which selectively recognizes oligosaccharides terminating in NeuAc alpha 2-6Gal in N-glycans. Sequence similarity between these proteins is highest within their first four amino-terminal Ig-like domains. Here we identify the domain(s) containing the binding sites of both molecules by generating a series of extracellular domain deletion mutants fused to the Fc portion of human IgG1. Binding activity was analyzed by solid phase cell adhesion assays and also by surface plasmon resonance using purified glycophorin and CD45 as ligands for sialoadhesin and CD22, respectively. For sialoadhesin, the amino-terminal V-set Ig-like domain was both necessary and sufficient to mediate sialic acid-dependent adhesion of the correct specificity. In contrast, for murine CD22, only constructs containing both the V-set domain and the adjacent C2-set domain were able to mediate sialic acid-dependent binding. These results are consistent with the sialic acid binding site for both proteins residing in the membrane distal V-set domain, but for CD22 a direct contribution in binding from the neighboring C2-set domain cannot be excluded.

Apart from being used as food, seed oils have also been used traditionally as medicinal products by several communities. However, the full medicinal potential of many seed oil plants is yet to be properly reviewed, particularly for their antimicrobial and antioxidant properties. North-East India has rich resources of seed oil plants. The availability of detailed information on these plants is quite limited. This review aims to explore and evaluate these seed oil plants of the North-East India with particular emphasis on their antimicrobial and antioxidant activities as well as chemical compositions. A comprehensive literature search on seed oil plants of this region has been performed. Seed oil yielding plants of thisregion can be categorized into two categories: plants that are used traditionally as sources of edible ormedicinal oils and plants that are used for purposes other than as sources of oils. Many seed oil plants of this region have been reported to possess antimicrobial and antioxidant properties, and to produce various types of compounds. This review also highlights the importance of these plants in contributing to the local as well as the national economy of India.

A wide repertoire of transmembrane proteins are proteolytically released from the cell surface by a process known as ‘ectodomain shedding’, under both normal and pathophysiological conditions. Little is known about the physiological mechanisms that regulate this process. As a model system, we have investigated the metalloproteinase-mediated cleavage of the hepatocyte growth factor receptor, Met. We show that epidermal growth factor (EGF) receptor activation, either directly by EGF or indirectly via the G-protein coupled receptor (GPCR) agonist lysophosphatidic acid (LPA), induces cleavage of Met through activation of the Erk MAP kinase signalling cascade. The tyrosine kinase activity of the EGFR was a prerequisite for this stimulation, since treatment of cells with a synthetic inhibitor of this receptor, AG1478, completely abrogated shedding. The metalloproteinase mediating Met cleavage was specifically inhibited by the tissue inhibitor of metalloproteinases (TIMP)-3, but not by TIMP-1 or TIMP-2. Furthermore, the level of Met shedding could be modulated by different cell-matrix interactions. Our results indicate that ectodomain shedding is a highly regulated process that can be stimulated by EGFR signalling pathways and integrin ligation.

Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types. Members of this family contain an amino-terminal metalloprotease domain followed by a disintegrin domain, a cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin domain of metargidin contains an RGD tripeptide sequence, suggesting that it may potentially interact with the integrin family of proteins. Here we identify integrin ligands for metargidin on haemopoietic cells, by using a chimeric protein containing the extracellular domain of metargidin fused to the Fc portion of human IgG. Binding activity to a panel of human cell lines was analysed by solid-phase cell-adhesion assays. Metargidin bound to a monocytic cell line, U937, and a T cell line, MOLT-4, in a specific manner. Adhesion was divalent cation- and temperature- dependent and strongly enhanced by Mn2+, all features of integrin-mediated binding. Using a panel of anti-integrin antibodies we show that alphavbeta3 is a ligand for metargidin on U937 cells. In contrast, for MOLT-4 cells, the integrin alpha5beta1 contributes to cell binding. Adhesion was mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited cell binding to both cell lines. The specificity of the interaction between both alphavbeta3 and alpha5beta1 and metargidin was further confirmed by solid-phase adhesion assays using purified recombinant integrins. These results together indicate that metargidin can function as a cell adhesion molecule via interactions with alphavbeta3 and alpha5beta1 integrins.

Multi-isotope imaging mass spectrometry (MIMS) is a new and generally applicable method for the study of DNA replication, lipid and protein turnover and cell fate in animals and humans. In a proof-of-principle study, MIMS was used to test the 'immortal strand hypothesis', which proposes that stem cells maintain a master genetic template that is protected from cancer-causing mutations. The hypothesis remains hotly debated, in part because of the difficulties involved in testing it experimentally. Stable isotope incorporation was viewed and measured by MIMS in mammalian intestinal cell division, Drosophila melanogaster lipid metabolism and human lymphopoiesis. In the auditory system, the mechanosensory hair cells of the inner ear convert sound-induced vibrations into electrical signals. The apical surface of a hair cell consists of stereocilia with a core of actin filaments that function as mechanosensors. It has been suggested that these actin filaments are replaced within two to three days by a treadmilling process. Using the newly developed multi-isotope imaging mass spectrometry (MIMS) technique, Zhang et al. quantify protein turnover in hair-cell stereocilia in vivo and find that turnover is slow throughout the stereocilia, except for the tip region, and does not involve a treadmilling process.

Motor proteins of the myosin family serve many important functions in eukaryotic cells and are central to actin-based motility. Our understanding of the mechanism of myosin action has been hampered by the lack of technology for simultaneously observing the structure and dynamics of biomolecules, but now Kodera et al. have used high-speed atomic force microscopy (HS-AFM) to directly observe myosin V moving along actin filaments with unprecedented time resolution. They obtain high-resolution movies that provide visual evidence supporting the 'swinging lever-arm' model for myosin motility. The high-resolution imaging possible using HS-AFM should make the technique broadly applicable in the fields of structural biology and single-molecule biology.

Macrophages have specialized functions in different tissue microenvironments such as lymphohaemopoietic organs and the nervous system. Recently, progress has been made in defining cellular and molecular properties of isolated and tissue macrophages in the developing and adult animal.