Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti.

This study employed subtractive proteomics and immunoinformatics to analyze the Wuchereria bancrofti proteome and identify potential therapeutic targets, with a focus on designing a vaccine against the parasite species. A comprehensive bioinformatics analysis of the parasite's proteome identified 51 probable therapeutic targets, among which "Kunitz/bovine pancreatic trypsin inhibitor domain-containing protein" was identified as the most promising vaccine candidate. The candidate protein was used to design a multi-epitope vaccine, incorporating B-cell and T-cell epitopes identified through various tools. The vaccine construct underwent extensive analysis of its antigenic, physical, and chemical features, including the determination of secondary and tertiary structures. Docking and molecular dynamics simulations were performed with HLA alleles, Toll-like receptor 4 (TLR4), and TLR3 to assess its potential to elicit the human immune response. Immune simulation analysis confirmed the predicted vaccine's strong binding affinity with immunoglobulins, indicating its potential efficacy in generating an immune response. However, experimental validation and testing of this multi-epitope vaccine construct would be needed to assess its potential against W. bancrofti and even for a broader range of lymphatic filarial infections given the similarities between W. bancrofti and Brugia.

Larvicidal activity of selected essential oil in synergized combinations against Aedes aegypti.

This study was conducted to attain an alternate plant essential oil (EO) based mosquito larvicide against the dengue vector Aedes aegypti. Here three plants were selected based on their local availability, safety and insecticidal properties. EOs were extracted from Syzygium aromaticum (Myrtaceae) flower buds, fruits of Illicium verum (Schisandraceae) and Trachyspermum ammi (Apiaceae) by hydro-distillation and tested against Ae. aegypti larvae individually and in combinations to find synergistic interactions. Chemical constituent analysis of EOs was done by GC/MS/MS analysis and the main constituents in T. ammi were thymol (93.58%) and terpinen-4-ol (2.16%), in S. aromaticum eugenol 56.32% and caryophyllene 17.91% and in I. verum trans-anethole 53.05% and p-anisaldehyde 12.47%. The EOs from T. ammi, I. verum and S. aromaticum and their top components thymol, trans-anethole and eugenol exhibited larvicidal activity with LC50 values 39.48, 41.30, 66.90, 59.76, 50.19 and 60.89 mgL-1 respectively against Ae. aegypti larvae. The values for the co-toxicity factors for the binary combinations of the EOs were > 20 showing synergistic interactions among the binary mixtures. The respective LC50 values for the 1:1 binary combinations (S. aromaticum + I. verum), (S. aromaticum + T. ammi) and (I. verum + T. ammi) were 49.07, 48.54 and 27.67 mgL-1. ß-cyclodextrin inclusion complex made with I. verum + T. ammi combination showed an LC50 value of 23.93 mgL-1. On the whole the outcome of this study draw attention to the capability of synergistic EO combinations to emerge as a safe and environment friendly effective larvicide to control Aedes mosquitoes.

Evaluation of indigenous plant extracts against larvae of Culex quinquefasciatus Say (Diptera: Culicidae).

This study investigates the larvicidal potential of indigenous plant extracts from commonly used medicinal herbs as an environmentally safe measure to control the filarial vector, Culex quinquefasciatus Say (Diptera: Culicidae). The early fourth-instar larvae of C. quinquefasciatus, reared in the laboratory, were used for larvicidal assay with water, hot water, acetone, chloroform, and methanol leaf, stem-bark, and flower extracts of Acacia arabica Willd. Sans, Cedrus deodara Roxb, Hibiscus rosa-sinensis L., Mangifera indica L., Nerium indicum Mill., Nicotiana tabacum Linn., Pongamia pinnata (L.) Pierre, and Solanum nigrum Linn. All plant extracts showed moderate larvicidal effects after 24 h of exposure at 1,000 ppm; however, the highest larval mortality was found in stem-bark hot water, acetone, and methanol extracts of C. deodara (LC50 = 133.85, 141.60, and 95.19 ppm, LC90 = 583.14, 624.19, and 639.99 ppm) and leaf hot water, acetone, methanol, and chloroform extracts of N. tabacum (LC50 = 76.27, 163.81, 83.38, and 105.85 ppm, LC90 = 334.72, 627.38, 709.51, and 524.39 ppm) against the larvae of C. quinquefasciatus, respectively. This is an ideal ecofriendly approach for the control of lymphatic filariasis vector, C. quinquefasciatus.

Evaluation of larvicidal and nymphicidal potential of plant extracts against Anopheles subpictus Grassi, Culex tritaeniorhynchus Giles and Aphis gossypii Glover.

The acetone, chloroform, ethyl acetate, hexane and methanol extracts of peel and leaf extracts of Citrus sinensis, Ocimum canum, Ocimum sanctum and Rhinacanthus nasutus were tested against fourth instar larvae of malaria vector, Anopheles subpictus Grassi, Japanese encephalitis vector, Culex tritaeniorhynchus Giles (Diptera: Culicidae) and feeding deterrence to nymphs of cotton pest, Aphis gossypii Glover (Homoptera: Aphididae). The larval and nymph mortality were observed after 24 h of exposure. All extracts showed moderate larvicidal and nymphicidal effects; however, the highest mortality was found in peel chloroform extract of C. sinensis, leaf ethyl acetate extracts of O. canum and O. sanctum and leaf chloroform extract of R. nasutus against the larvae of A. subpictus (LC(50) = 58.25, 88.15, 21.67 and 40.46 ppm; LC(90) = 298.31, 528.70, 98.34 and 267.20 ppm), peel methanol extract of C. sinensis, leaf methanol extract of O. canum, ethyl acetate extracts of O. sanctum and R. nasutus against the larvae of C. tritaeniorhynchus (LC(50) = 38.15, 72.40, 109.12 and 39.32 ppm; LC(90) = 184.67, 268.93, 646.62 and 176.39 ppm), peel hexane extract of C. sinensis, leaf methanol extracts of O. canum and R. nasutus and leaf ethyl acetate extract of O. sanctum against the nymph of A. gossypii (LC(50) = 162.89, 80.99, 73.27 and 130.19 ppm; LC(90) = 595.40, 293.33, 338.74 and 450.90 ppm), respectively. These results suggest that the peel methanol extracts of C. sinensis and O. canum, ethyl acetate leaf extract of O. sanctum and leaf chloroform and ethyl acetate extract of R. nasutus have the potential to be used as an ideal eco-friendly approach for the control of the A. subpictus, C. tritaeniorhynchus and A. gossypii.

Larvicidal potential of medicinal plant extracts against Anopheles subpictus Grassi and Culex tritaeniorhynchus Giles (Diptera: Culicidae).

Mosquito control is facing a threat due to the emergence of resistance to synthetic insecticides. Insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. The acetone, chloroform, ethyl acetate, hexane, methanol and petroleum ether extracts of leaf, flower and seed of Cassia auriculata L., Leucas aspera (Willd.), Rhinacanthus nasutus KURZ., Solanum torvum Swartz and Vitex negundo Linn. were tested against fourth instar larvae of malaria vector, Anopheles subpictus Grassi and Japanese encephalitis vector, Culex tritaeniorhynchus Giles (Diptera: Culicidae). The larval mortality was observed after 24 h of exposure. All extracts showed moderate larvicidal effects; however, the highest mortality was found in leaf petroleum ether, flower methanol extracts of C. auriculata, flower methanol extracts of L. aspera and R. nasutus, leaf and seed methanol extracts of S. torvum and leaf hexane extract of V. negundo against the larvae of A. subpictus (LC(50) = 44.21, 44.69, 53.16, 41.07, 35.32, 28.90 and 44.40 ppm; LC(90) = 187.31, 188.29, 233.18, 142.66, 151.60, 121.05 and 192.11 ppm, respectively) and against the larvae of C. tritaeniorhynchus (LC(50) = 69.83, 51.29, 81.24, 71.79, 44.42, 84.47 and 65.35 ppm; LC(90) = 335.26, 245.63, 300.45, 361.83, 185.09, 351.41 and 302.42 ppm, respectively). These results suggest that the leaf petroleum ether, flower methanol extracts of C. auriculata, leaf and seed methanol extracts of S. torvum and leaf hexane extract of V. negundo have the potential to be used as an ideal eco-friendly approach for the control of the A. subpictus and C. tritaeniorhynchus. This is the first report on the mosquito larvicidal activity of the medicinal plant extracts.

Interferon regulatory factor-1 regulates reconstituted extracellular matrix (rECM)-mediated apoptosis in human mammary epithelial cells.

Interactions between extracellular matrix (ECM) and mammary epithelial cells are critical for mammary gland homeostasis and apoptotic signaling. Interferon regulatory factor-1 (IRF-1) is a transcriptional regulator that promotes apoptosis during mammary gland involution and p53-independent apoptosis. We have recently shown that rapid cell surface tamoxifen (Tam) signaling promotes apoptosis in normal human mammary epithelial cells that were acutely damaged by expression of human papillomavirus type-16 E6 protein (*HMEC-E6). Apoptosis was mediated by recruitment of CREB-binding protein (CBP) to the gamma-activating sequence (GAS) element of the IRF-1 promoter, induction of IRF-1 and caspase-1/-3 activation. Here, we show that growth factor-depleted, reconstituted ECM (rECM), similar to Tam, promotes apoptosis in *HMEC-E6 cells through induction of IRF-1. Apoptosis was temporally associated with recruitment of CBP to the GAS element of the IRF-1 promoter, induction of IRF-1 expression and caspase-1/-3 activation. Small interfering RNA-mediated suppression of IRF-1 protein expression in *HMEC-E6 cells blocked (1) induction of IRF-1, (2) caspase-1/-3 activation and (3) apoptosis. These observations demonstrate that IRF-1 promotes rECM-mediated apoptosis and provide evidence that both rECM and rapid Tam signaling transcriptionally activate IRF-1 through recruitment of CBP to the IRF-1 GAS promoter complex.

Studies on sodium and potassium metabolism and subsequent influence on electrocardiogram in unilaterally adrenalectomized black Bengal goat (Capra hircus).

Unilateral adrenalectomy was performed in six black Bengal goat (Capra hircus)to study electrocardiograph in connection with mineral metabolism with special reference to sodium and potassium and some other factors of physiological importance. The parameters were studied at every 12 hrs interval upto 120 hrs and 24 hrs interval from 120 to 240 hrs. Physiological parameters, like body weight and rectal temperature, changed non-significantly (p < 0.05) after adrenalectomy. Among minerals, plasma sodium (p < 0.01) and plasma potassium (p < 0.05) concentration were changed significantly between hours leaving impression in ECG as widening of QRS complex and peaked T wave with increased amplitude found after unilateral adrenalectomy. Heart rate also increased significantly (p < 0.01) between hours.