The Dynamics of Cytoplasmic mRNA Metabolism.

For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are larger for short-tailed mRNAs that have previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities.

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough.

In females, Alzheimer's disease (AD) incidences increases as compared to males due to estrogen deficiency after menopause. Estrogen therapy is the mainstay therapy for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. Estrogen plays a crucial role in amyloid precursor protein (APP) processing and overall neuronal health by regulating various factors such as brain-derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain-associated protein (Daxx) translocation, glutamatergic excitotoxicity, Voltage-Dependent Anion Channel, Insulin-Like Growth Factor 1 Receptor, estrogen-metabolising enzymes and apolipoprotein E (ApoE) protein polymorphisms. All these factors impact the physiology of postmenopausal women. Estrogen replacement therapies play an important treatment strategy to prevent AD after menopause. However, use of these therapies may lead to increased risks of breast cancer, venous thromboembolism and cardiovascular disease. Various therapeutic approaches have been used to mitigate the effects of estrogen on AD. These include hormone replacement therapy, Selective Estrogen Receptor Modulators (SERMs), Estrogen Receptor Beta (ERß)-Selective Agonists, Transdermal Estrogen Delivery, Localised Estrogen Delivery, Combination Therapies, Estrogen Metabolism Modulation and Alternative Estrogenic Compounds like genistein from soy, a notable phytoestrogen from plant sources. However, mechanism via which these approaches modulate AD in postmenopausal women has not been explained earlier thoroughly. Present review will enlighten all the molecular mechanisms of estrogen and estrogen replacement therapies in AD. Along-with this, the association between estrogen, estrogen-metabolising enzymes and ApoE protein polymorphisms will also be discussed in postmenopausal AD.

Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells.

MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb group proteins in ES cells and shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.

A Concise Review on Natural Products and Their Derivatives for Breast Cancer Treatment.

Cancer is a leading cause of death worldwide. Among other cancers, breast cancer has been found to produce maximum number of cases in 2020. Different factors including geographical, genetic, hormonal, oral contraceptives and modern lifestyle could be responsible for the development of breast cancer and different pathways can be targeted for breast cancer treatment. The various conventional approaches used for the treatment of breast cancer including radiotherapy, chemotherapy, hormone and immunotherapy. But due to the side effects associated with these conventional treatments such as non-selectivity, multidrug resistance and bioavailability, there is a need for the development of better therapeutic agents for breast cancer treatment. Several natural products have been explored for breast cancer treatment. However, many of these natural products suffered from the limitations of poor water solubility and possess toxic side effects. To overcome these limitations, several structural analogs of natural products have been synthesized and possess potent anti-breast cancer effects with less side effects over their precursor molecules. In the present manuscript, we describe the pathogenesis of breast cancer, some potent natural products used in the treatment of breast cancer and their selected structural analogs possessing potent anti-breast cancer effects. Database such as Science direct, Pubmed and Google scholar were searched using keywords 'risk factors', 'screening methods','receptors', and 'natural products and derivatives', Registered clinical trials on selected natural products were also analyzed. Present study concludes that eight selected natural products and their derivatives possess wide potential to exhibit anti-breast cancer effects and could be explored further to develop better chemotherapeutic agents against breast cancer.

Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

Unveiling the Pharmacological and Nanotechnological Facets of Daidzein: Present State-of-the-Art and Future Perspectives.

Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4',7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.

Assessment of Health-Related Quality of Life in Chronic Kidney Disease Patients: A Hospital-Based Cross-Sectional Study.

Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD (p = 0.005). A similar pattern was observed in work status, sleep, and general health (p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue (p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant (p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.

Recent insight into the biological activities and SAR of quinolone derivatives as multifunctional scaffold.

Quinolones are a type of bicyclic privileged building block with immense therapeutic potential. They are known for their crucial role in modulating numerous diseases conditions. In the present review, quinolone and its derivatives with different pharmacological properties like antibacterial, anticancer, anti-HIV, antitubercular and antimalarial activities are described on the basis of their structure activity relationship studies. Literature is mainly focused on the structural changes responsible for the significant increase in the therapeutic profile of the quinolone scaffold and its derivatives. The substitution pattern in the scaffold responsible for a substantial rise in the potency of specific activity has also been discussed, while emphasizing their potential as lead molecule for the drug discovery and development. Moreover, updates of recent research findings on this scaffold are also discussed.

Decrypting the Potential of Nanotechnology-Based Approaches as Cutting-Edge for Management of Hyperpigmentation Disorder.

The abundant synthesis and accretion of melanin inside skin can be caused by activation of melanogenic enzymes or increase in number of melanocytes. Melasma is defined as hyperpigmented bright or dark brown spots which are symmetrically distributed and have serrated and irregular borders. The three general categories of pigmentation pattern include centro facial pattern, malar pattern, and mandibular pattern. Exposure to UV rays, heat, use of cosmetics and photosensitizing drugs, female sex hormonal therapies, aberrant production of melanocyte stimulating hormone, and increasing aesthetic demands are factors which cause the development of melasma disease. This review gives a brief overview regarding the Fitzpatrick skin phototype classification system, life cycle of melanin, mechanism of action of anti-hyperpigmenting drugs, and existing pharmacotherapy strategies for the treatment of melasma. The objectives of this review are focused on role of cutting-edge nanotechnology-based strategies, such as lipid-based nanocarriers, i.e., lipid nanoparticles, microemulsions, nanoemulsions, liposomes, ethosomes, niosomes, transfersomes, aspasomes, invasomes penetration-enhancing vesicles; inorganic nanocarriers, i.e., gold nanoparticles and fullerenes; and polymer-based nanocarriers i.e., polymeric nanoparticles, polymerosomes, and polymeric micelles for the management of hyperpigmentation.

Melamine contamination and associated health risks: Gut microbiota does make a difference.

Melamine is a nitrogenous organic compound containing high amounts of nitrogen, which is interpreted as high protein in various standard protein measuring tests, therefore added to foods to boost the protein content. Illegal addition of melamine has been in practice by food manufacturers, which leads to toxicity and stone formation in kidneys of individuals consuming melamine-contaminated milk products. A focused and thorough structured search of bibliographic databases for peer-reviewed researches reported in the literature was carried out with a focused attention on melamine contamination, associated health risks, and the role of gut microbiota. The overall outcomes of the research and review articles pertaining to searched keywords along with analysis of the interventions have been described employing a deductive qualitative content analysis approach. Current review focuses on the various health risks associated with consumption of melamine-contaminated foods and the need to develop better and effective methods for its testing. Moreover, the importance of gut microbiota in mediating toxicity due to melamine has also been discussed as there is a link between toxicity and activities of gut microbiota.

ASTILBIN: A PROMISING UNEXPLORED COMPOUND WITH MULTIDIMENSIONAL MEDICINAL AND HEALTH BENEFITS.

BACKGROUND: Many flavonoids have various beneficial actions like anti-inflammatory, anti-carcinogenic properties and many other clinical conditions. Astilbin is one such flavanoid compound having many physiological as well as pharmacological actions. PURPOSE: To summarize the important findings from the research conducted using astilbin having significance to its physiological and pharmacological activities as well as the patents filed using astilbin. STUDY DESIGN: Systematic review and compilation of the collected literature. METHOD: An extensive investigation of literature was done using several worldwide electronic scientific databases like PUBMED, SCOPUS, Science Direct and Google Scholar etc. All the article available in the English language that used our compound of interest i.e. astilbin, on the basis of inclusion criteria decided were retrieved from these databases, thoroughly reviewed and were summarized. RESULT: It has been established that astilbin can play a vital in the management of diseases associated with immune system. It also possesses antibacterial, anti-oxidative and hepatoprotective activity. CONCLUSION: These researches provide evidence that astilbin possesses great potential and thus can be utilized in the management of various disorders, thus establishing itself as a potential candidate for novel drug development. Also, there is still room for research on astilbin like it can be evaluated for anticancer potential, protective effect in various diabetic complications and many more. Overall observations from data suggested that astilbin is a promising compound and proved its efficacy in every preclinical study which is conducted till date. Some of the pharmacological activity is still unexplored. After successful preclinical trials, astilbin can go for further clinical trials.

Encapsulated miR-200c and Nkx2.1 in a nuclear/mitochondria transcriptional regulatory network of non-metastatic and metastatic lung cancer cells.

BACKGROUND: MicroRNAs are noncoding RNA molecules of ~ 22 nucleotides with diagnostic and therapeutic action [Curr Drug Targets, 2015. 16(12): p. 1381-403], affecting the expression of mRNAs involved in invasion, migration, and development [Oncotarget, 2015. 6(9): p. 6472-98, Cancer Manag Res, 2014. 6: p. 205-16]. miR-200c is part of the miR-200c/141 cluster on chromosome 12p13. Its mechanism of action when encapsulated is critical in lung cancer when patients express changes in miRNAs. miR-200c be a potential biomarkers for various lung diseases. As a potential therapy, miR-200c can impacts lives as target lung cancer is a leading cause of death with about 234,000 cases annually, high heterogeneity, complex screening, and a 5-year survival rate of 16% [CA Cancer J Clin, 2016.66(1): p. 7-30]. Encapsulated miR-200c efficiently enhances bioavailability, pharmacokinetics of therapeutics and targeting to cells, improves efficacy and provides potential cure. METHODS: The functions of miR-200c were determined in non-metastatic KW-634 and metastatic 821-T4 and 821-LN mouse lung cancer cell lines after various Nano vehicle treatments. Viability and cytotoxicity were determined by cell cycle and quantitative real-time PCR analyses were used to quantify levels of miR-200c and its target genes. In situ hybridization was used to visualize patterns of expression of miR-200c and others in the lung and many organs. Next-generation sequencing accession number GSE125000, invasion and migration assays using transwell chambers, and ActivSignal were used to elucidate the activation and inhibition profiles and perform direct expression measurements and modification of cellular components. RESULTS: Due to their effectiveness as intracellular vesicles transporting miR-200c into, out, and between parts of the cells, miR-200c is encapsulated with cholesterol, an integral part of the biological membranes with very important physical properties of the vehicle. Nano miR-200c showed efficient cellular uptake in KW-634, 821-T4, and 821-LN cells with important changes in gene expression and new isoforms. In KW-634, when treated with encapsulated miR-200c and compare to the non-encapsulated control; miR-29b increased by 5261-fold, and in 821-T4/LN, miR-1247 increased by 150-fold. Conversely, miR-1247 and miR-675 decreased by 348 and 1029.5-fold, respectively. miR-189 decreased by 34-fold in treated 821-T4 cells. A reduction of growth was observed only after 48 h of treatment with Nano miR-200c. Moreover, labeling the vehicle with carboxy-fluorescein showed that the encapsulated particles enter the nucleus and mitochondria. Encapsulated miR-200c by entering the cells, the nucleus and mitochondria, trigger changes in cell cycle phases with 4 up to 12 fold percentage in G2 and S phase respectively compare to miR-200c. Endogenous expression of Nkx2.1, miR-200c, and their targets Myb, Nfib, Six4 and Six1 showed an inverse correlation, as observed in development. CONCLUSIONS: Little is known about miR-200c involvement in regulatory processes. Nano miR-200c affects invasion and migration mechanisms. The expression of encapsulated miR-200c contributes to the inhibition/activation of Kras, EMT, Hippo, regulatory pathways and blockers of metastasis. Delivery of miR-200c increases the expression of miR-29b, an EMY regulator, and miR-1247, an inhibitor of cancer genes, both tumor suppressors involved in lung metastasis. Encapsulated miR-200c act on different proteins that regulates cell cycle pathways. These findings represent a part of a regulatory network providing new insights towards improvement of therapy.

miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion.

Whether epithelial-mesenchymal transition (EMT) is always linked to increased tumorigenicity is controversial. Through microRNA (miRNA) expression profiling of mammary epithelial cells overexpressing Twist, Snail or ZEB1, we identified miR-100 as a novel EMT inducer. Surprisingly, miR-100 inhibits the tumorigenicity, motility and invasiveness of mammary tumor cells, and is commonly downregulated in human breast cancer due to hypermethylation of its host gene MIR100HG. The EMT-inducing and tumor-suppressing effects of miR-100 are mediated by distinct targets. While miR-100 downregulates E-cadherin by targeting SMARCA5, a regulator of CDH1 promoter methylation, this miRNA suppresses tumorigenesis, cell movement and invasion in vitro and in vivo through direct targeting of HOXA1, a gene that is both oncogenic and pro-invasive, leading to repression of multiple HOXA1 downstream targets involved in oncogenesis and invasiveness. These findings provide a proof-of-principle that EMT and tumorigenicity are not always associated and that certain EMT inducers can inhibit tumorigenesis, migration and invasion.

Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation.

Retinoblastoma protein (pRB) mediates cell-cycle withdrawal and differentiation by interacting with a variety of proteins. RB-Binding Protein 2 (RBP2) has been shown to be a key effector. We sought to determine transcriptional regulation by RBP2 genome-wide by using location analysis and gene expression profiling experiments. We describe that RBP2 shows high correlation with the presence of H3K4me3 and its target genes are separated into two functionally distinct classes: differentiation-independent and differentiation-dependent genes. The former class is enriched by genes that encode mitochondrial proteins, while the latter is represented by cell-cycle genes. We demonstrate the role of RBP2 in mitochondrial biogenesis, which involves regulation of H3K4me3-modified nucleosomes. Analysis of expression changes upon RBP2 depletion depicted genes with a signature of differentiation control, analogous to the changes seen upon reintroduction of pRB. We conclude that, during differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters.

Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells.

Many long noncoding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin and regulation of these molecules in individual cell types is poorly understood. We have generated catalogs of lncRNA species expressed in human and murine embryonic stem cells and mapped their genomic origin. A surprisingly large fraction of these transcripts (>60%) originate from divergent transcription at promoters of active protein-coding genes. The divergently transcribed lncRNA/mRNA gene pairs exhibit coordinated changes in transcription when embryonic stem cells are differentiated into endoderm. Our results reveal that transcription of most lncRNA genes is coordinated with transcription of protein-coding genes.

Tat engagement of p38 MAP kinase and IRF7 pathways leads to activation of interferon-stimulated genes in antigen-presenting cells.

As a result of its interaction with transcription factors, HIV type 1 (HIV-1) Tat can modulate the expression of both HIV and cellular genes. In antigen-presenting cells Tat induces the expression of a subset of interferon (IFN)-stimulated genes (ISGs) in the absence of IFNs. We investigated the genome-wide Tat association with promoters in immature dendritic cells and in monocyte-derived macrophages. Among others, Tat associated with the MAP2K6, MAP2K3, and IRF7 promoters that are functionally part of IL-1 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. The association correlated with their increased gene expression, increased activation of p38 MAPK and of phosphorylated signal transducer and activator of transcription 1 (STAT1), and consequent induction of ISGs. Probing these pathways with RNA interference, pharmacological p38 MAPK inhibition, and in cell lines lacking STAT1s or the type I IFN receptor chain confirmed the role of MAPKKs and IRF7 in Tat-mediated modulation of ISGs and excluded the involvement of IFNs in this modulation. Tat interaction with the 2 MAPKK and IRF7 promoters in HIV-1-infected cells and the resulting persistent activation of ISGs, which include inflammatory cytokines and chemokines, can contribute to the increased immune activation that characterizes HIV infection.

Whole-body MRI of juvenile spondyloarthritis: protocols and pictorial review of characteristic patterns.

Spondyloarthritides are a group of inflammatory rheumatological diseases that cause arthritis with a predilection for spinal or sacroiliac involvement in addition to a high association with HLA-B27. Juvenile spondyloarthritis is distinct from adult spondyloarthritis and manifests more frequently as peripheral arthritis and enthesitis. Consequently juvenile spondyloarthritis is often referred to as enthesitis-related arthritis (ERA) subtype under the juvenile idiopathic arthritis (JIA) classification criteria. The American College of Rheumatology Treatment Recommendations for JIA, including ERA, are based on the following clinical parameters: current treatment, disease activity and the presence of poor prognostic features. The MRI features of juvenile spondyloarthritis include marrow edema, peri-enthesal soft-tissue swelling and edema, synovitis and joint or bursal fluid. Marrow edema is nonspecific and can be seen with other pathologies as well as in healthy subjects, and this is an important pitfall to consider. With further longitudinal study and validation, however, whole-body MRI with dedicated images of the more commonly affected areas such as the spine, sacroiliac joints, hips, knees, ankles and feet can serve as a more objective tool compared to clinical exam for early detection and monitoring of disease activity and ultimately direct therapeutic management.

Neuroprotective effect of Spirulina fusiform and amantadine in the 6-OHDA induced Parkinsonism in rats.

BACKGROUND: Multi-factorial etiology exists in pathophysiology of neurodegenerative diseases. The imbalance of anti-oxidant enzymes and dopamine level leads to Parkinsonism. The objective of this study was to assess the protective effect of Spirulina fusiform alone and in combination with amantadine against Parkinsonism effect in 6-hydroxydopamine (6-OHDA) induced rat model. METHODS: S. fusiform was administered in different groups (500 mg/kg, once daily and twice daily) and a combination of spirulina (500 mg/kg, once daily) with amantadine (20 mg/kg once daily) for 30 days before and 14 days after a single injection of 6-OHDA into the dorsal striatum. Post lesion produced rotational behavior which was measured at two week intervals (37th and 44th day). Locomotors activity was also done at 44th and muscle coordination at 48th day. Dorsal striatum was isolated from rat brain for evaluating the antioxidant assays and dopamine content at 49th day. RESULTS: Both the body rotations (ipsilateral and contralateral) were found to have a statistically significant (p<0.001) decrease by 34.26 and 52% after treatment with spirulina (Twice a day) in spirulina treated lesioned group. A higher percentage of improvement was shown in the reduction of ipsilateral (57.34%) and contralateral (78.3%) rotations in combination of spirulina with amantadine treated lesioned group rather than spirulina alone treated lesioned groups when compared with positive control lesioned group. Body movements and locomotor activity were improved statistically (p<0.0001) significant in both treated lesioned groups (Combination of spirulina with amantadine and spirulina twice daily). Similar results were also seen in anti-oxidant levels which later on reached to the normal value. The levels of dopamine content had a statistically significant (p<0.0001) increase by 78.3% only in case of spirulina with amantadine treated lesioned group. CONCLUSION: Spirulina is a potent nutraceutical supplement all over the world, so my preclinical study may contribute to give an additional adjuvant drug therapy in aging related disorders (Neurodegenerative as well as diabetes associated neurodegenerative disorders).

Development and optimization of polymeric self-emulsifying nanocapsules for localized drug delivery: design of experiment approach.

The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil), X2 (polymeric emulsifier), and X3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1) and encapsulation efficiency (Y2) of the formulation. Polymeric nanocapsules with an average diameter of 100-180 nm and an encapsulation efficiency of 64.85±0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (C max 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0-2 h in upper GIT; 2-4 h in small intestine; and 4-24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 µM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.

Insights into Prospects of Novel NSAID Prodrugs in the Management of Gastrointestinal Toxicity: A Perspective Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) have a long history in the healthcare system due to their therapeutic potential. These NSAIDs cause ulcerogenicity, stomach pains, gastrointestinal hemorrhage, mucosa bleeding, and pancreatitis when used moderately and consistently. With researchers, managing the aforementioned adverse effects therapeutically is getting increasingly difficult. One method for creating NSAID moieties with low penetration as well as ulcerogenic properties is the prodrug technique. During the oral consumption of NSAID-prodrugs, ulcerations, intestinal hemorrhage, and mucosa hemorrhage have significantly decreased. Considering this background, this review focussed on NSAID prodrugs as well as their justifications, the pathogenesis of NSAIDs inducing gastrointestinal toxicity, and the role of different antioxidants and spacer groups. Prodrug moieties have more advantages over parent medicines concerning both solubility and lipophilicity. In general, NSAID-class prodrugs can successfully treat both acute and long-term inflammation and aches without causing ulcerotoxicity and related gastrointestinal side effects, which reduces their burden from the pharmacoeconomic perspective.