AMPK activates the Nrf2-Keap1 pathway to govern dendrite pruning via the insulin pathway in Drosophila.

During Drosophila metamorphosis, the ddaC dendritic arborisation sensory neurons selectively prune their larval dendrites in response to steroid hormone ecdysone signalling. The Nrf2-Keap1 pathway acts downstream of ecdysone signalling to promote proteasomal degradation and thereby dendrite pruning. However, how the Nrf2-Keap1 pathway is activated remains largely unclear. Here, we demonstrate that the metabolic regulator AMP-activated protein kinase (AMPK) plays a cell-autonomous role in dendrite pruning. Importantly, AMPK is required for Mical and Headcase expression and for activation of the Nrf2-Keap1 pathway. We reveal that AMPK promotes the Nrf2-Keap1 pathway and dendrite pruning partly via inhibition of the insulin pathway. Moreover, the AMPK-insulin pathway is required for ecdysone signalling to activate the Nrf2-Keap1 pathway during dendrite pruning. Overall, this study reveals an important mechanism whereby ecdysone signalling activates the Nrf2-Keap1 pathway via the AMPK-insulin pathway to promote dendrite pruning, and further suggests that during the nonfeeding prepupal stage metabolic alterations lead to activation of the Nrf2-Keap1 pathway and dendrite pruning.

An Update of Lectins from Marine Organisms: Characterization, Extraction Methodology, and Potential Biofunctional Applications.

Lectins are a unique group of nonimmune carbohydrate-binding proteins or glycoproteins that exhibit specific and reversible carbohydrate-binding activity in a non-catalytic manner. Lectins have diverse sources and are classified according to their origins, such as plant lectins, animal lectins, and fish lectins. Marine organisms including fish, crustaceans, and mollusks produce a myriad of lectins, including rhamnose binding lectins (RBL), fucose-binding lectins (FTL), mannose-binding lectin, galectins, galactose binding lectins, and C-type lectins. The widely used method of extracting lectins from marine samples is a simple two-step process employing a polar salt solution and purification by column chromatography. Lectins exert several immunomodulatory functions, including pathogen recognition, inflammatory reactions, participating in various hemocyte functions (e.g., agglutination), phagocytic reactions, among others. Lectins can also control cell proliferation, protein folding, RNA splicing, and trafficking of molecules. Due to their reported biological and pharmaceutical activities, lectins have attracted the attention of scientists and industries (i.e., food, biomedical, and pharmaceutical industries). Therefore, this review aims to update current information on lectins from marine organisms, their characterization, extraction, and biofunctionalities.

Implementation of Flexible Work Arrangement among Healthcare Workers in Miri Hospital-Assessment of the Validity and Reliability of Flexible Work Arrangement Perceived Benefits and Barriers Scale, and the Exploratory Study.

Background: Flexible work arrangements (FWAs) have been widely implemented during the COVID-19 pandemic. We aimed to assess the validity and reliability of the FWA perceived benefits and barriers (FWAPB) scale and subsequently, to determine the preference and perceived feasibility, perceived benefits and barriers, and readiness to implement FWA among healthcare workers. Methods: We conducted a cross-sectional study using a self-administered questionnaire in Miri Hospital. The questionnaire was administered via a web survey design (Google Forms). The convenience sampling method was applied to recruit respondents. All healthcare workers in Miri Hospital who could read and understand English were invited to participate in the study. Response process validation, exploratory factor analysis, reliability analyses and descriptive statistics were performed. Results: A total of 339 respondents participated. All items had satisfactory response process indices. Exploratory factor analysis revealed a three-factor structure. Items of 'perceived benefits-workplace management', 'perceived benefits-family life balance' and 'perceived barriers' have high internal consistency reliability (Cronbach's alpha = 0.852-0.884) and factor loadings. Flextime is preferred and perceived to be the most feasible work arrangement. Most agreed that FWA helps in improving social distancing among colleagues (mean = 3.65, standard deviation [SD] = 0.99) and reduces their exposure to COVID-19 (mean = 3.60, SD = 1.06). A total of 44.0% of the respondents agreed Miri Hospital is ready to implement FWA. Conclusion: The FWAPB is valid and reliable. Almost half of the respondents were positive towards the implementation of FWA. These findings contribute to the understanding of FWA, and thus increase the readiness and acceptance of such an arrangement.

Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor.

A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.Key points• An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.• PGL protected PC12 nerve cells from the toxicity of corticosterone.• PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.

Factors Associated with Intention to Donate Hematopoietic Stem Cells among Blood Donors.

INTRODUCTION: Past studies pay little attention to the intention to donate hematopoietic stem cells (HSC) among blood donors. This study investigated the level of and the influence of socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC among blood donors. METHODS: This cross-sectional study recruited blood donors at selected public hospitals in the Malaysian State of Sarawak in 2019. A structured questionnaire was developed based on the review of relevant literature. It gathered information on socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC. Variables with a p value <0.200 in bivariate analysis were included in the variable selection for regression modeling to examine their associations with the intention to donate HSC. RESULTS: A total of 569 blood donors participated (94.5% response rate). Overall, 87.1% reported a positive intention to donate HSC. In the regression model, the factor with the greatest association with intention to donate HSC was subjective norms about HSC donation (ß = 0.35, 95% CI 0.27-0.42), followed by attitude about regulations of HSC donation (ß= 0.21, 95% CI 0.13-0.35), self-efficacy on HSC donation (ß = 0.15, 95% CI 0.09-0.32), attitude about the potential side effects of HSC donation (ß = 0.14, 95% CI 0.02-0.10) and highest education level (ß = 0.10, 95% CI 0.03-0.44). CONCLUSIONS: The findings can be used to formulate a better strategy in promoting HSC donation among blood donors in the region.

Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer.

BACKGROUND: Previous studies have shown a major green tea polyphenol (-)-epigallocatechin-3-gallate ((-)-EGCG) as a powerful anti-cancer agent. However, its poor bioavailability and requirement of a high dosage to manifest activity have restricted its clinical application. Recently, our team synthesized a peracetate-protected derivative of EGCG, which can act as a prodrug of (-)-EGCG (ProEGCG) with enhanced stability and improved bioavailability in vitro and in vivo. Herein, we tested the therapeutic efficacy of this novel ProEGCG, in comparison to EGCG, toward human endometrial cancer (EC). METHODS: In this study, the effects of ProEGCG and EGCG treatments on cell growth, cell survival and modulation of intracellular signaling pathways in RL95-2 and AN3 CA EC cells were compared. The antiproliferative effect was evaluated by cell viability assay. Apoptosis was measured by annexin/propidium iodide staining. Expression of mitogen-activated protein kinases, markers of proliferation and apoptosis were measured by immunoblot analysis. In addition, the effects of ProEGCG and EGCG on tumor growth, vessel formation and gene expression profiles on xenograft models of the EC cells were investigated. RESULTS: We found that treatment with ProEGCG, but not EGCG, inhibited, in a time- and dose-dependent manner, the proliferation and increased apoptosis of EC cells. Treatment with low-dose ProEGCG significantly enhanced phosphorylation of JNK and p38 MAPK and inhibited phosphorylation of Akt and ERK which are critical mediators of apoptosis. ProEGCG, but not EGCG, elicited a significant decrease in the growth of the EC xenografts, promoted apoptotic activity of tumour cells in the EC xenografts, and decreased microvessel formation, by differentially suppressing anti-apoptotic molecules, NOD1 and NAIP. Notably, no obvious adverse effects were detected. CONCLUSIONS: Taken together, ProEGCG at a low dose exhibited anticancer activity in EC cells through its anti-proliferative, pro-apoptotic and anti-tumor actions on endometrial cancer in vitro and in vivo. In contrast, a low dose of EGCG did not bring about similar effects. Importantly, our data demonstrated the efficacy and safety of ProEGCG which manifests the potential of a novel anticancer agent for the management of endometrial cancer.

Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials.

This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew's ear (black) fungus or black wood ear fungus Auricularia auricula-judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep's head mushroom Grifola frondosa, lion's mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese "meshimakobu," Chinese "song gen," Korean "sanghwang," American "black hoof mushroom"), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.

New ribosome-inactivating proteins and other proteins with protein synthesis-inhibiting activities.

Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.

The impact of serostatus disclosure on spousal relationships between wives and HIV-positive husbands who have sex with men in China.

This study explored the impact of serostatus disclosure on the spousal relationship between wives and their HIV-positive husbands who have had sex with men. A qualitative study using semi-structured interviews was conducted in Sichuan, China in 2017 with wives (n = 31) who had known their husbands' HIV-positive status. Participants were identified by local governmental and non-governmental organizations that provide routine services for people living with HIV and their family members. Qualitative data underwent a detailed content analysis. Both positive and negative impacts on the spousal relationship were expressed by wives. Six themes were identified: (1) reduced sexual activities; (2) changes in intimacy; (3) limited communication on HIV-related issues but improved communication on other topics; (4) increased instrumental support but decreased emotional support; (5) improved resilience in the spousal relationship; and (6) shared privacy management rules regarding HIV-positive status. Moreover, the acknowledgment of the husband's homosexual behavior hurt the spousal relationship more seriously than the disclosure of the husband's HIV-positive status, and irremediable marriages were observed among wives who knew both. Disclosure of HIV-positive status had a great impact on the spousal relationship, though such impact varied across individuals.

Diversity of potentially exploitable pharmacological activities of the highly prized edible medicinal fungus Antrodia camphorata.

Antrodia camphorata, also known as A. cinnamomea, is a precious medicinal basidiomycete fungus endemic to Taiwan. This article summarizes the recent advances in research on the multifarious pharmacological effects of A. camphorata. The mushroom exhibits anticancer activity toward a large variety of cancers including breast, cervical, ovarian, prostate, bladder, colorectal, pancreatic, liver, and lung cancers; melanoma; leukemia; lymphoma; neuroblastoma; and glioblastoma. Other activities encompass antiinflammatory, antiatopic dermatitis, anticachexia, immunoregulatory, antiobesity, antidiabetic, antihyperlipidemic, antiatherosclerotic, antihypertensive, antiplatelet, antioxidative, antiphotodamaging, hepatoprotective, renoprotective, neuroprotective, testis protecting, antiasthmatic, osteogenic, osteoprotective, antiviral, antibacterial, and wound healing activities. This review aims to provide a reference for further development and utilization of this highly prized mushroom.

LncRNAs with miRNAs in regulation of gastric, liver, and colorectal cancers: updates in recent years.

Long noncoding RNA (lncRNA) is a kind of RNAi molecule composed of hundreds to thousands of nucleotides. There are several major types of functional lncRNAs which participate in some important cellular pathways. LncRNA-RNA interaction controls mRNA translation and degradation or serves as a microRNA (miRNA) sponge for silencing. LncRNA-protein interaction regulates protein activity in transcriptional activation and silencing. LncRNA guide, decoy, and scaffold regulate transcription regulators of enhancer or repressor region of the coding genes for alteration of expression. LncRNA plays a role in cellular responses including the following activities: regulation of chromatin structural modification and gene expression for epigenetic and cell function control, promotion of hematopoiesis and maturation of immunity, cell programming in stem cell and somatic cell development, modulation of pathogen infection, switching glycolysis and lipid metabolism, and initiation of autoimmune diseases. LncRNA, together with miRNA, are considered the critical elements in cancer development. It has been demonstrated that tumorigenesis could be driven by homeostatic imbalance of lncRNA/miRNA/cancer regulatory factors resulting in biochemical and physiological alterations inside the cells. Cancer-driven lncRNAs with other cellular RNAs, epigenetic modulators, or protein effectors may change gene expression level and affect the viability, immortality, and motility of the cells that facilitate cancer cell cycle rearrangement, angiogenesis, proliferation, and metastasis. Molecular medicine will be the future trend for development. LncRNA/miRNA could be one of the potential candidates in this category. Continuous studies in lncRNA functional discrepancy between cancer cells and normal cells and regional and rational genetic differences of lncRNA profiles are critical for clinical research which is beneficial for clinical practice.

A hemagglutinin isolated from Northeast China black beans induced mitochondrial dysfunction and apoptosis in colorectal cancer cells.

Incidence of colorectal cancer is closely related with the lifestyle, especially the dietary habits of patients. Epidemiological researches have demonstrated a negative correlation between legume consumption and colorectal cancer incidence. Lectins/hemagglutinins are a type of carbohydrate binding proteins which are abundantly stored in legumes. Their eminent pH-stability allows them to survive digestion and remain active in the intestine where they may have direct contact with colorectal tumors. It is therefore interesting to explore the direct interaction between lectins/hemagglutinins and colorectal cancer. In the present research, we reported a detailed research on the interaction between a hemagglutinin isolated from an edible legume with two colorectal cancer cell lines. This hemagglutinin (NCBBH) was found to first bind to tumor cell membrane as early as 30min post treatment and was gradually transported inside the cytoplasm within 3h, with some of it localized in the Golgi apparatus and some in the lysosomes. After its entrance, the hemagglutinin induced aggregation of the Golgi apparatus, which in turn adversely affected the transportation of protein from endoplasmic reticulum (ER) to the Golgi apparatus, resulting in protein accumulation in ER and ER stress. The hemagglutinin-treated cells also manifested severe mitochondrial malformation and membrane depolarization, accompanied by obvious apoptosis characteristics, like chromatin condensation, phosphatidylserine exposure and caspase activation. Collectively, our results indicate that the hemaggltuinin could successfully enter the cytoplasm of colorectal cancer cells and adversely affect their growth, providing a mechanism in support of the application of edible legumes to the prevention and treatment of colorectal cancer.

Down-regulation of TIMP2 by HIF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma.

UNLABELLED: Cancer metastasis is a multistep process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling, which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases (TIMP) 2 in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly down-regulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.8%; 23 of 55) in human HCCs and was significantly associated with liver invasion and poorer survival outcomes of HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Using an orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line, MHCC-97L, significantly reduced HCC progression as well as pulmonary metastasis. Mechanistically, TIMP2 suppression, in a hypoxic environment, was induced through a regulatory feedback circuit consisting of hypoxia-inducible factor (HIF) 1 alpha, microRNA-210 (miR-210), and HIF-3α. CONCLUSION: TIMP2 is frequently down-regulated in human HCCs and its down-regulation is associated with aggressive tumor behavior and poorer patient outcome. Its suppression is under the regulation of a novel feedback circuit consisting of HIF-1α/miR-210/HIF-3α. TIMP2 is an important regulator of ECM degradation and HCC metastasis. (Hepatology 2016;64:473-487).

Therapeutic potentials of short interfering RNAs.

Short interfering RNA (siRNA) is one of the members of the family of RNA interference (RNAi). Coupled with the RNA-induced silencing complex (RISC), siRNA is able to trigger the cleavage of target RNAs which serve as a defensive system against pathogens. Meanwhile, siRNA in gene silencing opens a new avenue for the treatment of various diseases. SiRNA can effectively inhibit viral infection and replication and suppress tumorigenesis and various inflammation-associated diseases and cardiovascular diseases by inactivation of viral genes and downregulation of oncogene expression. Recently, endogenous siRNAs (endo-siRNAs) were discovered in the reproductive cells of animals which may be associated with regulation of cell division. Structural modification of siRNA enhances the delivery, specificity and efficacy and bioavailability to the target cells. There are at least five categories of siRNA delivery systems including viral vectors, lipid-based nanoparticles, peptide-based nanoparticles, polymer-based nanoparticles and inorganic small molecules like metal ions, silica and carbon. Sufficient preclinical and clinical studies supported that siRNA may be a potential medicine for targeted therapy of various diseases in the near future.

A Thioether-Stabilized d-Proline-l-Proline-Induced ß-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability.

We report a ß-hairpin dual stabilizing strategy: a d-proline-l-proline (d-Pro-l-Pro) dipeptide as the nucleating turn, and a thioether tether as a side-chain linkage at a precisely designed position to stabilize the ß-hairpin. This method was used to modify the C-terminal ß-hairpin moiety of the plant defensin, pv-defensin, in order to obtain a stabilized peptide with enhanced anti-Candida albicans activity (MIC 84-3.0 µm), high serum stability (50 % remaining after 48 h) and low hemolysis (<10 % at 152 µm). This modified peptide penetrated the C. albicans cell membrane within 5 min and showed high activity against clinically isolated antibiotic-resistant C. albicans and Candida glabrata strains.

A Cullin1-based SCF E3 ubiquitin ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning.

Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning.

The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth.

Drosophila larval brain neuroblasts divide asymmetrically to balance between self-renewal and differentiation. Here, we demonstrate that the SCF(Slimb) E3 ubiquitin ligase complex, which is composed of Cul1, SkpA, Roc1a and the F-box protein Supernumerary limbs (Slimb), inhibits ectopic neuroblast formation and regulates asymmetric division of neuroblasts. Hyperactivation of Akt leads to similar neuroblast overgrowth and defects in asymmetric division. Slimb associates with Akt in a protein complex, and SCF(S)(limb) acts through SAK and Akt to inhibit neuroblast overgrowth. Moreover, Beta-transducin repeat containing, the human ortholog of Slimb, is frequently deleted in highly aggressive gliomas, suggesting a conserved tumor suppressor-like function.

Snake venom toxins: toxicity and medicinal applications.

Snake venoms are complex mixtures of small molecules and peptides/proteins, and most of them display certain kinds of bioactivities. They include neurotoxic, cytotoxic, cardiotoxic, myotoxic, and many different enzymatic activities. Snake envenomation is a significant health issue as millions of snakebites are reported annually. A large number of people are injured and die due to snake venom poisoning. However, several fatal snake venom toxins have found potential uses as diagnostic tools, therapeutic agent, or drug leads. In this review, different non-enzymatically active snake venom toxins which have potential therapeutic properties such as antitumor, antimicrobial, anticoagulating, and analgesic activities will be discussed.

Marine natural products with anti-inflammatory activity.

Chronic inflammation is believed to play crucial roles in the pathogenesis of various diseases. Several types of drugs are used to treat inflammatory disorders, but they cause adverse side effects. Natural products are alternatives to these drugs which offer hope for discovery of bioactive lead compounds that may be developed into drugs for treatment of inflammatory disorders. The biological and chemical diversity of marine habitats constitutes a sizeable reservoir of novel compounds. Some of them, like sesquiterpenoids, diterpenes, steroids, polysaccharides, alkaloids, fatty acids, proteins, and other chemical compounds, isolated from marine organisms are found to exhibit anti-inflammatory activity. This review reports some recent (2011-2015) investigations and examples of marine natural products and their synthetic derivatives with anti-inflammatory activity. It also highlights those compounds that are currently undergoing preclinical or clinical evaluation.