Dr. Hari Singh Gour University

There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3'-dihydroxy-β, β'-carotene-4,4'-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications.

Several cancers are highly refractory to conventional chemotherapy. The survival of tumors in several cases is assisted by checkpoint immunomodulation to maintain the imbalance between immune surveillance and cancer cell proliferation. Check point antibody inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. These checkpoint blockers are rapidly becoming a highly promising cancer therapeutic approach that yields remarkable antitumor responses with limited side effects. In recent times, more than four check point antibody inhibitors have been commercialized for targeting PD-1, PDL-1, and CTLA-4. Despite the huge success and efficacy of the anti-PD therapy response, it is limited to specific types of cancers, which attributes to the insufficient and heterogeneous expression of PD-1 in the tumor microenvironment. Herein, we review the current landscape of the PD-1/PD-L1 mechanistic role in tumor immune evasion and therapeutic outcome for cancer treatment. We also review the current progress in clinical trials, combination of drug therapy with immunotherapy, safety, and future of check point inhibitors for multiple types of cancer.

Thirteen new patients and 174 patients previously reported with coronary arteriovenous fistula (CAVF) were reviewed to delineate the course and management of CAVF and to clarify the role of surgical ligation in the young asymptomatic patient. Patients were grouped according to age: 99 patients (four new and 95 reported) were less than 20 years old and 88 (nine new and 79 reported) were greater than or equal to 20 years old. Of those under 20 years of age, 19% had preoperative symptoms or CAVF-related complications, including congestive heart failure (CHF) in 6%, subacute bacterial endocarditis in 3% and death in one patient. Seventy-six patients younger than 20 years old had CAVF ligation with only one significant complication. In contrast, 63% of the older group and all of our nine older patients had preoperative symptoms or complications, including CHF in 19%, SBE in 4%, myocardial infarction (MI) in 9%, death in 14% and fistula rupture in one patient. Of the 43 ligated older patients, 23% had surgical complications, including MI in three and death in three. Mean pulmonic-to-systemic flow in the entire group was 1.6:1 and did not differ significantly in those with or without symptoms or complications. One of our patients and one previously reported had spontaneous CAVF closure. In summary, early elective ligation of CAVF is indicated in all patients because of the high incidence of late symptoms and complications and the increased morbidity and mortality associated with ligation in older patients.

Microalgae can be used as a source of alternative food, animal feed, biofuel, fertilizer, cosmetics, nutraceuticals and for pharmaceutical purposes. The extraction of organic constituents from microalgae cultivated in the different nutrient compositions is influenced by microalgal growth rates, biomass yield and nutritional content in terms of lipid and fatty acid production. In this context, nutrient composition plays an important role in microalgae cultivation, and depletion and excessive sources of this nutrient might affect the quality of biomass. Investigation on the role of nitrogen and phosphorus, which are crucial for the growth of algae, has been addressed. However, there are challenges for enhancing nutrient utilization efficiently for large scale microalgae cultivation. Hence, this study aims to highlight the level of nitrogen and phosphorus required for microalgae cultivation and focuses on the benefits of nitrogen and phosphorus for increasing biomass productivity of microalgae for improved lipid and fatty acid quantities. Furthermore, the suitable extraction methods that can be used to utilize lipid and fatty acids from microalgae for biofuel have also been reviewed.

PURPOSE: Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides. To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper gastrointestinal tract (GIT) and then be abruptly released into the proximal colon, which is considered the optimum site for colon-targeted delivery of drugs. Colon targeting is naturally of value for the topical treatment of diseases of colon such as Chron's diseases, ulcerative colitis, colorectal cancer and amebiasis. Peptides, proteins, oligonucleotides and vaccines pose potential candidature for colon targeted drug delivery. METHODS: The various strategies for targeting orally administered drugs to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymers, formulation of timed released systems, exploitation of carriers that are degraded specifically by colonic bacteria, bioadhesive systems and osmotic controlled drug delivery systems. Various prodrugs (sulfasalazine, ipsalazine, balsalazine and olsalazine) have been developed that are aimed to deliver 5-amino salicylic acid (5-ASA) for localized chemotherapy of inflammatory bowl disease (IBD). Microbially degradable polymers especially azo crosslinked polymers have been investigated for use in targeting of drugs to colon. Certain plant polysaccharides such as amylose, inulin, pectin and guar gum remains unaffected in the presence of gastrointestinal enzymes and pave the way for the formulation of colon targeted drug delivery systems. The concept of using pH as a rigger to release a drug in the colon is based on the pH conditions that vary continuously down the gastrointestinal tract. Times dependent drug delivery systems have been developed that are based on the principle to prevent release of drug until 3-4 h after leaving the stomach. Redox sensitive polymers and bioadhesive systems have also been exploited to deliver the drugs into the colon. RESULTS: The approach that is based on the formation of prodrug involves covalent linkage between drug and carrier. The type of linkage that is formed between drug and carrier would decide the triggering mechanism for the release of drug in colon. The presence of azo reductase enzymes play pivotal role in the release of drug from azo bond prodrugs while glycosidase activity of the colonic microflora is responsible for liberation of drugs from glycosidic prodrugs. Release of drugs from azo polymer coated dosage forms is supposed to take place after reduction and thus cleavage of the azo bonds by the azoreductase enzymes present in the colonic microflora. Natural polysaccharides have been used as tools to deliver the drugs specifically to the colon. These polysaccharides remain intact in the physiological environment of stomach and small intestine but once the dosage form enters into colon, it is acted upon by polysaccharidases, which degrades the polysaccharide and releases the drug into the vicinity of bioenvironment of colon. However, they should be protected while gaining entry into stomach and small intestine due to enormous swelling and hydrophilic properties of polysaccharides. This has been achieved either by chemical crosslinking or by addition of a protective coat. Formulation coated with enteric polymers releases drug when pH move towards alkaline range while as the multicoated formulation passes the stomach, the drug is released after a lag time of 3-5 h that is equivalent to small intestinal transit time. Drug coated with a bioadhesive polymer that selectively provides adhesion to the colonic mucosa may release drug in the colon. CONCLUSIONS: Improved drug delivery systems are required for drugs currently in use to treat localized diseases of the colon. The advantages of targeting drugs specifically to the diseased colon are reduced incidence of systemic side effects, lower dose of drug, supply of the drug to the biophase only when it is required and maintenance of the drug in its intact form as close as possible to the target site.

Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic analogues, belong to the flavonoid family, which possess a number of interesting biological properties such as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Several pure chalcones have been approved for clinical use or tested in humans. Clinical trials have shown that these compounds reached reasonable plasma concentration and are well-tolerated. For this reason they are an object of continuously growing interest amongst the scientists. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to provide an overview of the pharmacological activity of naturally occurring and synthetic chalcones. This review highlights more recent pharmacological screening of these compounds, their mechanisms of action and relevant structure-activity relationships.

belonging to the family zingiberaceae. Growing experimental evidence revealed that curcumin exhibit multitarget biological implications signifying its crucial role in health and disease. The current review highlights the recent progress and mechanisms underlying the wide range of pharmacological effects of curcumin against numerous diseases like neuronal, cardiovascular, metabolic, kidney, endocrine, skin, respiratory, infectious, gastrointestinal diseases and cancer. The ability of curcumin to modulate the functions of multiple signal transductions are linked with attenuation of acute and chronic diseases. Numerous preclinical and clinical studies have revealed that curcumin modulates several molecules in cell signal transduction pathway including PI3K, Akt, mTOR, ERK5, AP-1, TGF-β, Wnt, β-catenin, Shh, PAK1, Rac1, STAT3, PPARγ, EBPα, NLRP3 inflammasome, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Curcumin has a potential to prevent and/or manage various diseases due to its anti-inflammatory, anti-oxidant and anti-apoptotic properties with an excellent safety profile. In contrast, the anti-cancer effects of curcumin are reflected due to induction of growth arrest and apoptosis in various premalignant and malignant cells. This review also carefully emphasized the pharmacokinetics of curcumin and its interaction with other drugs. Clinical studies have shown that curcumin is safe at the doses of 12 g/day but exhibits poor systemic bioavailability. The use of adjuvant like piperine, liposomal curcumin, curcumin nanoparticles and curcumin phospholipid complex has shown enhanced bioavailability and therapeutic potential. Further studies are warranted to prove the potential of curcumin against various ailments.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Dendrimers in Oncology: An Expanding HorizonRakesh Kumar Tekade, Palanirajan Vijayaraj Kumar, and Narendra Kumar Jain*View Author Information Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar-470 003, India* To whom correspondence should be addressed. E-mail: [email protected]. Tel./Fax: +91-7582-264712.Cite this: Chem. Rev. 2009, 109, 1, 49–87Publication Date (Web):December 19, 2008Publication History Received12 December 2006Published online19 December 2008Published inissue 14 January 2009https://pubs.acs.org/doi/10.1021/cr068212nhttps://doi.org/10.1021/cr068212nreview-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views13355Altmetric-Citations415LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cells,Conjugate acid-base pairs,Dendrons,Toxicity,Tumors Get e-Alerts

siRNA is a promising therapeutic solution to address gene overexpression or mutations as a post-transcriptional gene regulation process for several pathological conditions such as viral infections, cancer, genetic disorders, and autoimmune disorders like arthritis. This therapeutic method is currently being actively pursued in cancer therapy because siRNA has been found to suppress the oncogenes and address mutations in tumor suppressor genes and elucidate the key molecules in cellular pathways in cancer. It is also effective in personalized gene therapy for several diseases due to its specificity, adaptability, and broad targeting capability. However, naked siRNA is unstable in the bloodstream and cannot efficiently cross cell membranes besides being immunogenic. Therefore, careful design of the delivery systems is essential to fully utilize the potential of this therapeutic solution. This review presents a comprehensive update on the challenges of siRNA delivery and the current strategies used to develop nanoparticulate delivery systems.

Abstract Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1 . Remote-sensing estimates to quantify carbon losses from global forests 2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced 6 and satellite-derived approaches 2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea 2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.

This work describes the use of a novel vesicular drug carrier system called transfersomes, which is composed of phospholipid, surfactant, and water for enhanced transdermal delivery. The transfersomal system was much more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. In the present study transfersomes and liposomes were prepared by using dexamethasone as a model drug. The system was evaluated in vitro for vesicle shape and size, entrapment efficiency, degree of deformability, number of vesicles per cubic mm, and drug diffusion across the artificial membrane and rat skin. The effects of surfactant type, composition, charge, and concentration of surfactant were studied. The in vivo performance of selected formulation was evaluated by using a carrageenan-induced rat paw edema model. Fluorescence microscopy by using rhodamine-123 and 6-carboxyfluorescein as fluorescence probe was performed. The stability study was performed at 4 degrees C and 37 degrees C. An in vitro drug release study has shown a nearly zero order release of drug and no lag phase. The absence of lag phase in comparison to liposomes and ointment is attributed to the greater deformability, which may account for better skin permeability of transfersomes. In vivo studies of transfersomes showed better antiedema activity in comparison to liposomes and ointment, indicating better permeation through the penetration barrier of the skin. This was further confirmed through a fluorescence microscopy study. Finally, it may be concluded from the study that complex lipid molecules, transfersomes, can increase the transdermal flux, prolong the release, and improve the site specificity of bioactive molecules.

The 1,3,4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.

Among heterocyclic compounds, quinoline scaffold has become an important construction motif for the development of new drugs. Quinoline and its derivatives possess many types of biological activities and have been reported to show significant anticancer activity. Quinoline compounds play an important role in anticancer drug development as they have shown excellent results through different mechanism of action such as growth inhibitors by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration and modulation. A number of quinoline derivatives have been reported till date for their anticancer activity. The present review, summarizes various mono-, di-, tri-, tetra- and heterocyclic substituent quinoline derivatives with potential anticancer activity. Their mechanism of action and possible structure activity relationship has also been discussed. Keywords: Anticancer, Quinoline, Quinoline derivatives, Structure-activity relationship

), a popular food spice and flavoring agent, has also been used traditionally to treat various ailments especially bacterial infections for centuries in various cultures around the world. The principal phytochemicals that exhibit antibacterial activity are oil-soluble organosulfur compounds that include allicin, ajoenes, and allyl sulfides. The organosulfur compounds of garlic exhibit a range of antibacterial properties such as bactericidal, antibiofilm, antitoxin, and anti-quorum sensing activity against a wide range of bacteria including multi-drug resistant (MDR) strains. The reactive organosulfur compounds form disulfide bonds with free sulfhydryl groups of enzymes and compromise the integrity of the bacterial membrane. The World Health Organization (WHO) has recognized the development of antibiotic resistance as a global health concern and emphasizes antibiotic stewardship along with the urgent need to develop novel antibiotics. Multiple antibacterial effects of organosulfur compounds provide an excellent framework to develop them into novel antibiotics. The review provides a focused and comprehensive portrait of the status of garlic and its compounds as antibacterial agents. In addition, the emerging role of new technologies to harness the potential of garlic as a novel antibacterial agent is discussed.

Poor solubility and hydrophobicity of drugs/bioactives limit their possible applications in drug delivery and formulation development. Apart from conventional methods of solubility enhancement, there are some novel methods which can be used in solubilization. Dendrimers represent a novel type of polymeric material that has generated much interest in many diverse areas due to their unique structure and properties. Dendrimer-mediated solubility enhancement mainly depends on factors such as generation size, dendrimer concentration, pH, core, temperature, and terminal functionality. Added advantage in solubilization can be achieved considering these factors. Available literature suggests that ionic interaction, hydrogen bonding, and hydrophobic interactions are the possible mechanisms by which a dendrimer exerts its solubilizing property. This review presents various mechanisms and reports relating to solubility enhancement using dendrimers. Also, micellar behavior and future possibilities in relation to solubilization via dendrimers are included.

Microalgae are rich source of various bioactive molecules such as carotenoids, lipids, fatty acids, hydrocarbons, proteins, carbohydrates, amino acids, etc. and in recent Years carotenoids from algae gained commercial recognition in the global market for food and cosmeceutical applications. However, the production of carotenoids from algae is not yet fully cost effective to compete with synthetic ones. In this context the present review examines the technologies/methods in relation to mass production of algae, cell harvesting for extraction of carotenoids, optimizing extraction methods etc. Research studies from different microalgal species such as Spirulina platensis, Haematococcus pluvialis, Dunaliella salina, Chlorella sps., Nannochloropsis sps., Scenedesmus sps., Chlorococcum sps., Botryococcus braunii and Diatoms in relation to carotenoid content, chemical structure, extraction and processing of carotenoids are discussed. Further these carotenoid pigments, are useful in various health applications and their use in food, feed, nutraceutical, pharmaceutical and cosmeceutical industries was briefly touched upon. The commercial value of algal carotenoids has also been discussed in this review. Possible recommendations for future research studies are proposed.

The interaction between the human microbiome and immune system has an effect on several human metabolic functions and impacts our well-being. Additionally, the interaction between humans and microbes can also play a key role in determining the wellness or disease status of the human body. Dysbiosis is related to a plethora of diseases, including skin, inflammatory, metabolic, and neurological disorders. A better understanding of the host-microbe interaction is essential for determining the diagnosis and appropriate treatment of these ailments. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by removing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform. Culturing large numbers of microbial taxa in the laboratory is problematic at best, if not impossible. Consequently, this makes it very difficult to comprehensively catalog the individual members comprising a specific microbiome, as well as understanding how microbial communities function and influence host-pathogen interactions. Recent advances in sequencing technologies and computational tools have allowed an increasing number of metagenomic studies to be performed. These studies have provided key insights into the human microbiome and a host of other microbial communities in other environments. In the present review, the role of the microbiome as a therapeutic agent and its significance in human health and disease is discussed. Advances in high-throughput sequencing technologies for surveying host-microbe interactions are also discussed. Additionally, the correlation between the composition of the microbiome and infectious diseases as described in previously reported studies is covered as well. Lastly, recent advances in state-of-the-art bioinformatics software, workflows, and applications for analysing metagenomic data are summarized.

Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients.

Ligand-mediated targeting of drugs especially in anticancer drug delivery is an effective approach. Dendrimers, due to unique surface topologies, can be a choice in this context. In the present study, PAMAM (polyamidoamine) dendrimers up to fourth generation were synthesized and characterized through infrared (IR), nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectrometric, and transmission electron microscopic (TEM) techniques. Primary amines present on the dendritic surface were conjugated through folic acid and folic acid-PEG (poly(ethylene glycol))-NHS (N-hydroxysuccinimide) conjugates. Tumor in mice was induced through the use of KB cell culture. Prepared dendritic conjugates were evaluated for the anticancer drug delivery potential using 5-FU (5-fluorouracil) in tumor-bearing mice. Approximately 31% of 5-FU was loaded in folate-PEG-dendritic conjugates. Results indicated that folate-PEG-dendrimer conjugate was significantly safe and effective in tumor targeting compared to a non-PEGylated formulation. Tailoring of dendrimers via PEG-folic acid reduced hemolytic toxicity, which led to a sustained drug release pattern as well as highest accumulation in the tumor area.

Plants in nature are constantly exposed to a variety of abiotic and biotic stresses which limits their growth and production. Enhancing crop yield and production to feed exponentially growing global population in a sustainable manner by reduced chemical fertilization and agrochemicals will be a big challenge. Recently, the targeted application of beneficial plant microbiome and their cocktails to counteract abiotic and biotic stress is gaining momentum and becomes an exciting frontier of research. Advances in next generation sequencing (NGS) platform, gene editing technologies, metagenomics and bioinformatics approaches allows us to unravel the entangled webs of interactions of holobionts and core microbiomes for efficiently deploying the microbiome to increase crops nutrient acquisition and resistance to abiotic and biotic stress. In this review, we focused on shaping rhizosphere microbiome of susceptible host plant from resistant plant which comprises of specific type of microbial community with multiple potential benefits and targeted CRISPR/Cas9 based strategies for the manipulation of susceptibility genes in crop plants for improving plant health. This review is significant in providing first-hand information to improve fundamental understanding of the process which helps in shaping rhizosphere microbiome.