Konarev AV et al. (2002) Phytochemistry "Serine proteinase inhibitors in the Compositae: distribution, polymorphism and properties."

Anisimova IN, Shewry PR, Vachrusheva TE, Konechnaya GY, Gavrilova VA, Lewis M, Konarev AV

[Phytochemistry, 2002]

Multiple molecular forms of inhibitors of trypsin (TI) and chymotrypsin (CI), which are typical digestive enzymes of insects, mammals and micro-organisms, and subtilisin (SI), a proteinase of many bacteria and phytopathogenic fungi, were identified in seeds and vegetative organs of the majority of 128 wild and cultivated species representing 65 genera of three of the subfamilies of the Compositae. Inhibitors with M(r) ranging from 7450 to 7800 and combining activities towards subtilisin and trypsin and/or chymotrypsin (T/C/SI) had the widest distribution and may be involved in plant defense mechanisms. They were found in many species of the subfamilies Carduoideae (genera Carthamus, Centaurea, Cirsium), Cichorioideae (Lactuca, Taraxacum) and Asteroideae (Helianthus, Cosmos, Bidens). Partial amino acid sequencing showed that the safflower (Carthamus tinctorius) T/C/SI and Cosmos bipinnatus T/C/SI, T/SI and C/SI belonged to the potato I inhibitor family. The most active, variable and heterogeneous inhibitors were found in species of the tribe Heliantheae, which is placed in the evolutionary advanced subfamily Asteroideae. Seeds of Helianthus species, Eclipta prostrata, Gailardia aristata, Zinnia elegans and Silphium perfoliatum contained various TI with M(r) ranging from 1500 to 14,750, with some also containing SI. H. annuus seeds contain a unique cyclic TI of M(r) 1514 and similar TI were also present in other Helianthus spp. and the related species Tithonia diversifolia. Zinnia elegans contained a TI with M(r) 11,350 which appeared to represent a novel type of inhibitor distantly related to the cereal subgroup of Bowman-Birk inhibitors. TI and T/SI varied widely in H. annuus lines and wild Helianthus species in their presence or absence and composition. Similar T/SI components were found in the cultivated diploid H. annuus and annual diploid species with the B genome but not in perennials with the A genome. Some T/SI, SI and TI were detected in vegetative organs of sunflower and other Compositae. Studies of the polymorphism and distribution of proteinase inhibitors are relevant to the evolution of protective protein systems and the mechanisms of resistance to pathogenic organisms in the Compositae and other plants.

Ali MM et al. (2003) J Infect Dis "Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history."

AbdelRahman SI, Baraka OZ, Mackenzie CD, Sulaiman SM, Ali MM, Williams JF, Homeida MM

[J Infect Dis, 2003]

The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses.

Yang S et al. (2019) J Comput Biol "Three-Dimensional Embryonic Image Segmentation and Registration Based on Shape Index and Ellipsoid-Fitting Method."

Chen Y, Han X, Yang S

[J Comput Biol, 2019]

Quantitative analysis based on three-dimensional differential interference contrast (DIC) images is currently the mainstream in analyzing gene functions involved in early cell fate specifications. Segmentation and registration are the two most important steps in analysis. Many image segmentation methods have poor performance on embryonic DIC images because of the interference of egg shells, blurs, and nonuniform intensity background. A novel segmentation method is presented based on the shape index (SI) of local intensity variation in DIC images. To compute the SI, the intensity values of a local neighborhood are regarded as z coordinates over x-y planes. After calculating the SI for each pixel by evaluating the shape of intensity surface over the corresponding local neighborhood, SI thresholding is used to detect cytoplasm granules within embryonic boundaries. As a scalar and rotation invariant, the SI is both insensitive to directional changes and different ranges of intensity variations. Embryonic registration methods are usually based on the orientation of vertebrate anteroposterior (AP) axes computed from segmented embryonic boundaries. Due to the blur of marginal slices in DIC images, usually the segmented boundaries are incomplete, which may make the computed AP axes shift away from the correct orientation when using the principal component analysis method. A method calculating AP axes based on ellipsoid-fitting is proposed, which can achieve high accuracy when handling incomplete segmented boundaries. Using Worm Developmental Dynamics Database, we evaluated the performance of the proposed segmentation method and the computation of AP axes. Experimental results show that the two methods outperform existing methods.

Liu Y et al. (2012) J Pharmacol Sci "Activated O2() and H2O2 mediated cell survival in SU11274-treated non-small-cell lung cancer A549 cells via c-Met-PI3K-Akt and c-Met-Grb2/SOS-Ras-p38 pathways."

Liu Y, Ikejima T, Ye YC, Onodera S, Shi QF, Tashiro SI

[J Pharmacol Sci, 2012]

The pharmacological activity of SU11274 is primarily due to its inhibition of hepotocyte growth factor receptor (c-Met) kinase overexpression. In this study, we demonstrated that the pathway involved in SU11274-induced autophagy was presumably through inhibition of c-Met and its down-stream pathways, including phosphatidylinositol 3-kinases Akt (PI3KAkt) and the growth factor receptor bound protein-2 / son of sevenless Ras p38 MAPK (Grb2/SOSRasp38) pathway. SU11274 time-dependently induced the generation of superoxide anion (O2()) and hydrogen peroxide (H2O2). There is a negative feedback loop between reactive oxygen species (ROS) induction and SU11274. Then, we investigated the role of ROS in protecting cells against SU11274-induced autophagic cell death in A549 cells. O2() and H2O2 generation activated c-MetPI3KAkt and c-MetGrb2/SOSRasp38 signaling pathways, which were suppressed by O2() scavenger superoxide dismutase (SOD) and H2O2 scavenger catalase. In conclusion, O2() and H2O2 evoked cell resistance to SU11274 via activating c-MetPI3KAkt and c-MetGrb2/SOSRasp38 pathways in A549 cells. SU11274 also induced ROS generation in Caenorhabditis elegans.

Atjanasuppat K et al. (2009) J Ethnopharmacol "In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand."

Bartlett A, Atjanasuppat K, Whitfield PJ, Kittakoop P, Meepowpan P, Sobhon P, Wongkham W

[J Ethnopharmacol, 2009]

AIM OF STUDY: This study screened for anthelmintic and/or antitumour bioactive compounds from Thai indigenous plants and evaluated effectiveness against three different worm species and two cancer cell lines. MATERIALS AND METHODS: Methylene chloride and methanol extracts of 32 plant species were screened for in vitro anthelmintic activity against three species of worms, the nematode Caenorhabditis elegans, the digeneans Paramphistomum epiclitum and Schistosoma mansoni (cercariae). Cytotoxicity of the extracts was evaluated against two cancer cell lines: human amelanotic melanoma (C32) and human cervical carcinoma (HeLa) by the SRB assay. Anthelmintic and anticancer activities were evaluated by the inhibiting concentration at 50% death (IC(50)) and the selectivity index (SI) relative to human fibroblasts. RESULTS AND CONCLUSIONS: None of the extracts were active against Paramphistomum epiclitum. Plumbagin, a pure compound from Plumbago indica, had the strongest activity against Caenorhabditis elegans. The methylene chloride extract of Piper chaba fruits had the strongest activity against schistosome cercariae. Strong cytotoxicity was shown by the methylene chloride extract of Michelia champaca bark and the methanol extract of Curcuma longa rhizome against C32 and HeLa, respectively. These extracts had higher SI (>100) than positive controls in relation to either the worms or the cell lines. The methanol extract of Bouea burmanica had a slightly lower activity towards C32 cells than did Michelia champaca but had a much higher SI (>27,000). ETHNOPHARMACOLOGICAL RELEVANCE: The plant species screened in this research was recorded by several indigenous medicinal practitioners as antiparasitic, anticancer and/or related activities to the human major organ system.

Li H et al. (2022) Sci Total Environ "Direct toxicity of environmentally persistent free radicals to nematode Caenorhabditis elegans after excluding the concomitant chemicals."

Liu Y, Li H, Steinberg C, Zuo N, Pan B, Lang D, Xing B

[Sci Total Environ, 2022]

Environmentally persistent free radicals (EPFRs) have attracted extensive attention due to their potential toxicity. However, EPFRs-containing particles always coexist with their parent organic contaminants and intermediate degradation products (IM), which may have hindered the toxicity assessment of EPFRs. In this study, the toxicity of EFFRs was specifically verified after comparing the systems without EPFRs, such as the immediate mixture of catechol (CT) and particles, solutions of CT only, IM extracted from the particles, as well as particles after EPFRs quenching. Caenorhabditis elegans (C. elegans) were used as model organisms. Our results showed that EPFRs-containing particles (Si-Al-CT) exhibited significant toxicity to C. elegans, but not for the parent chemical CT and IM on the particles. Higher levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the Si-Al-CT system were attributed to the mediated generation of -O₂^- and -OH via EPFRs. EPFRs could increase gene expressions related not only to oxidative stress and biotransformation in C. elegans, but also to indications of disturbances in energy homeostasis, survival, proliferation, cell and embryonic development. Overall, these results confirmed the direct toxicity of EPFRs and highlighted the key role of EPFRs which may be neglected in assessing the environmental risks of organic contaminants.

Balasubramaniyan M et al. (2015) Int J Biol Macromol "Immunopotentiating nano-chitosan as potent vaccine carter for efficacious prophylaxis of filarial antigens."

Santhanam M, Perumal K, Devasena T, Balasubramaniyan M

[Int J Biol Macromol, 2015]

Lymphatic filariasis (LF), a morbid vector-borne parasitic infection affects millions in tropical areas. Complete eradication can only be achieved by the development of a potent vaccine. Among the various filarial antigens that have been characterized, antigens Brugia malayi thioredoxin (TRX) and abundant larval transcript (ALT) have produced recognizable level of protection in Jirds, thereby evidenced to be good vaccine candidates. In this study an attempt was made to enhance their immunoprophylactic activity by encapsulating them in natural polysaccharide chitosan forming nanospheres (CN). High encapsulation efficiency for TRX (93%) in CN (TCN) and ALT-2 (90%) in CN (ACN) was achieved. Morphological studies confirmed the spherical and uniform distribution of nanospheres to be 220 nm. The electrostatic interaction between chitosan and the antigens were confirmed using differential scanning calorimetry and FT-IR. The study revealed the immunostimulatory property of chitosan providing enhanced level of proliferation for encapsulated antigens in peripheral blood mononuclear cells from endemic normal personals, at low concentration (TCN mean stimulation index (SI)=4.23+/-0.15 and ACN (SI)=4.05+/-0.33) compared to stimulation obtained by antigens alone. Hence, our study demonstrated that natural macromolecule derived CN can be used as efficacious immunostimulatory vaccine carter for LF thereby diminishing pathological sequel.

Fang Z et al. Indian J Med Microbiol "A recombinant plasmid of composite cysteine proteinase inhibitor/glyceraldehyde-3-phosphate dehydrogenase gene of periodic Brugia malayi functions on DNA immunity in the host."

Lu SJ, Wang YY, Fang H, Fang Z, Xu Q, Wu JQ

[Indian J Med Microbiol]

OBJECTIVES: Both cysteine proteinase inhibitors (CPIs) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) play important roles in the pathogenesis of parasites and their relationship with the hosts. We constructed a new eukaryotic recombinant expression plasmid pcDNA3.1(+)-BmCPI/BmGAPDH of periodic Brugia malayi for investigation of the DNA vaccine-elicited immune responses. MATERIALS AND METHODS: We cloned a gene encoding the CPIs and GAPDH from periodic B. malayi into vector pcDNA3.1. The composited plasmid or the control was injected into the tibialis anterior muscle of the hind leg in BALB/c mice, respectively. The target genes were detected by reverse transcription-polymerase chain reaction in muscle tissues. The stimulation index (SI) of T-lymphocyte proliferation and the levels of interferon-gamma (INF-g) and interleukin-4 ( IL-4) in serum were detected by thiazolyl blue tetrazolium blue and enzyme-linked immunosorbent assays. RESULTS: The pcDNA3.1(+)-BmCPI/BmGAPDH was amplified from muscle tissues of the mice after immunisation. The SI of the immunised group was significantly higher than that of the two control groups (P < 0.05). The levels of INF-g and IL-4 of pcDNA3.1(+)-BmCPI/BmGAPDH group were both higher than those of the two control groups (P < 0.05). The level of INF-g of pcDNA3.1(+)-BmCPI/BmGAPDH group was significantly higher than that of pcDNA3.1(+)-BmCPI/CpG group (P < 0.05). CONCLUSIONS: We conclude that the recombinant plasmid pcDNA3.1(+)-BmCPI/BmGAPDH could elicit specific humoural and cellular immune responses in mice.

Wang HJ et al. (2010) Free Radic Res "Silibinin induces the generation of nitric oxide in human breast cancer MCF-7 cells."

Zang LH, Huang H, Ikejima T, Fan SM, Jiang YY, Tashiro SI, Yang Y, Onodera S, Wang HJ, Wei XF

[Free Radic Res, 2010]

Increasing research has concentrated on the anti-tumour efficacy of silibinin, a flavonolignan that is clinically used as an hepatoprotectant. However, previous work has found that silibinin-induced apoptosis is accompanied by protective superoxide (O(2)*-) generation in MCF-7 cells. This study further reports the formation of reactive nitrogen species (RNS) in the same system. It finds that silibinin induces nitric oxide (*NO) generation in a time- and concentration-dependent manner. Moreover, the results support that there exists an inter-regulation pattern between RNS and reactive oxygen species (ROS) generation. In addition, silibinin is also found to induce RNS and ROS generation in the isolated populations of mouse peripheral blood mononuclear cells (PBMCs) and a simple in vivo model of Caenorhabditis elegans.

Mahalakshmi N et al. (2013) Parasitol Res "Molecular characterization and evaluation of Onchocerca volvulus-secreted larval acidic protein 1 (SLAP1) as a putative vaccine candidate on endemic population of lymphatic filariasis."

Aparnaa R, Mahalakshmi N, Ansel Vishal L, Kaliraj P

[Parasitol Res, 2013]

Filarial parasites infected nearly 160 million of the global population with onchocerciasis and lymphatic filariasis, and further, a billion of people are estimated to be at risk of infection, rendering them among the most prevalent infectious agents in the world today. Given the complexity of their life cycle and the immune evasion mechanisms of these organisms, development of a vaccine remains to be a long-term challenge. Though a number of immunodominant antigens have been characterized, the presence of homologous proteins in humans or the allelic variants are some of the major drawbacks. One of the extensively studied vaccine candidates is abundant larval transcripts (ALT) family of proteins for the following properties: highly regulated expression, abundance, excreted-secreted product of infective stage larvae, and essentially for parasite establishment and survival in the host. In the present study, stage-specific expression of secreted larval acidic protein 1 (SLAP1) was identified; an ALT orthologue from Onchocerca volvulus was cloned, expressed, and purified as a recombinant protein. Immunogenicity of OvSLAP1 was demonstrated with sera and peripheral blood mononuclear cells from endemic regions of Brugia malayi and Wuchereria bancrofti. OvSLAP1 antibodies were predominated by IgG1 and IgG2 in endemic normal (EN) and chronic pathology (CP) subjects. It has also induced marked cellular response as observed by lymphoproliferation assay. The study revealed that OvSLAP1 can segregate humoral (EN mean optical density (OD)=0.87+/-0.035, CP mean OD=0.59+/-0.029) and cellular (EN mean stimulation index (SI)=5.87+/-0.167, CP mean SI=3.5+/-0.134) immune responses between EN and CP individuals (P<0.001), signifying its prophylactic ability and vitality for protection from filarial infections in endemic population.