In present investigation, differential expression of transcriptome after classical swine fever (CSF) vaccination has been explored at the cellular level in crossbred and indigenous (desi) piglets. ...RNA Sequencing by Expectation-Maximization (RSEM) package was used to quantify gene expression from RNA Sequencing data, and differentially expressed genes (DEGs) were identified using EBSeq, DESeq2, and edgeR softwares. After analysis, 5222, 6037, and 6210 common DEGs were identified in indigenous post-vaccinated verses pre-vaccinated, crossbred post-vaccinated verses pre-vaccinated, and post-vaccinated crossbred verses indigenous pigs, respectively. Functional annotation of these DEGs showed enrichment of antigen processing-cross presentation, B cell receptor signaling, T cell receptor signaling, NF-κB signaling, and TNF signaling pathways. The interaction network among the immune genes included more number of genes with greater connectivity in vaccinated crossbred than the indigenous piglets. Higher expression of
IRF3
,
IL1β
,
TAP1
,
CSK
,
SLA2
,
SLADM
, and
NF-kB
in crossbred piglets in comparison to indigenous explains the better humoral response observed in crossbred piglets. Here, we predicted that the processed CSFV antigen through the T cell receptor signaling cascade triggers the B cell receptor-signaling pathway to finally activate MAPK kinase and NF-κB signaling pathways in B cell. This activation results in expression of genes/transcription factors that lead to B cell ontogeny, auto immunity and immune response through antibody production. Further, immunologically important genes were validated by qRT-PCR.
After ban on single-use plastics, completely bio-based coating on paper is in great demand to replace the plastics liner and other organic-inorganic hybrid coating. To resolve the issues like ...moisture, hydrophilicty and repulpability after use, a green, sustainable and hydrophobic bio-coating material for paper substrate has been developed. In this work, silanized castor oil (SCO) and silanized methyl ricinoleate (SMR) bio-resins are synthesized by structural modifications of epoxidized castor oil through transesterification and silanization process, Subsequently, the silylated bio-resins are hydrolysed and subjected to crosslinking with cellulosic paper substrate through condensation process. The coated papers showed hydrophobicity with water contact angle (WCA) up to 97° and strongly moisture resistant (moisture content of 2–3%) nature. Scanning electron microscopy analysis with energy dispersive X-ray spectra confirms the uniform coating of SMR resin with better texture and higher degree of silane grafting. The water vapor transmission rate (WVTR) decreased by 77.5% after coating because of blockage of pores and strong bonding with the cellulosic fibers. Further the coated papers showed adequate thermal stability and better tensile strength for commercial packaging. These coatings are removed by exposing to strong alkali solution at 90 °C and the recyclability potential of the paper is confirmed for reuse. These renewable resourced and eco-friendly coating materials are found to be suitable alternative for paper packaging and other coating applications with circular economy approach.
Display omitted
•Methyl esters of castor oil based bio-coating material is developed for paper substrate for packaging.•Hydrolyzed silylated resins with higher silane grafting were crosslinked with cellulose.•Coated papers showed improved hydrophobicity and moisture resistant property.•Coatings are removed from the paper and the repulpable potential of the paper has been explored.
The aim of the current study is to simulate the long-term spatiotemporal soil moisture variation in the lower Mahanadi basin using the Soil and Water Assessment Tool (SWAT) model. The model was ...calibrated and validated using stream discharge data for the periods from 2005 to 2012 and 2013 to 2017, respectively. The coefficient of determination (
R
2
) and Nash–Sutcliffe-Efficiency (NSE) values were 0.81 and 0.79 during calibration, and 0.78 and 0.74 during validation. The spatiotemporal annual and seasonal soil moisture content maps were prepared sub-basin-wise for the study period (2005–2017). The depth of the simulated soil moisture content varies with the rainfall, land use, and soil types of the lower Mahanadi basin. The upper region of the lower Mahanadi basin shows a higher simulated soil moisture content compared to the downstream region. The amounts of average annual rainfall in agricultural land, barren land, deciduous forest, and wasteland were 416.25, 439.06, 403.04, and 409.90 mm, respectively, which correspond to 118.18, 111.48, 126.78, and 121.50 mm/m of soil moisture content. The seasonal soil moisture maps showed that after harvesting the
kharif
rice crop, a sufficient amount of soil moisture was available during the post-monsoon season. Therefore, short-duration pulses and oilseed crops are recommended in this region to utilize the residual simulated soil moisture content, which could bring unutilized areas into cultivation and enhance farmer’s income. Further, the simulated soil moisture content was compared with the satellite-derived SMAP-based soil moisture content, and a reasonably good agreement was found between the observed and simulated soil moisture content. The overall result showed that the SWAT model can reasonably simulate the spatiotemporal variation of soil moisture content.
Surface attachment of a planktonic bacteria, mediated by adhesins and extracellular polymeric substances (EPS), is a crucial step for biofilm formation. Some pathogens can modulate cell adhesiveness, ...impacting host colonization and virulence. A framework able to quantify cell-surface interaction forces and their dependence on chemical surface composition may unveil adhesiveness control mechanisms as new targets for intervention and disease control. Here we employed InP nanowire arrays to dissect factors involved in the early stage biofilm formation of the phytopathogen Xylella fastidiosa. Ex vivo experiments demonstrate single-cell adhesion forces up to 45 nN, depending on the cell orientation with respect to the surface. Larger adhesion forces occur at the cell poles; secreted EPS layers and filaments provide additional mechanical support. Significant adhesion force enhancements were observed for single cells anchoring a biofilm and particularly on XadA1 adhesin-coated surfaces, evidencing molecular mechanisms developed by bacterial pathogens to create a stronger holdfast to specific host tissues.
Cancer is one of the major causes of death worldwide. In spite of achieving significant successes in medical sciences in the past few decades, the number of deaths due to cancer remains unchecked. ...The conventional chemotherapy and radiotherapy have limited therapeutic index and a plethora of treatment related side effects. This situation has provided an impetus for search of novel therapeutic strategies that can selectively destroy the tumour cells, leaving the normal cells unharmed. Viral oncotherapy is such a promising treatment modality that offers unique opportunity for tumour targeting. Numerous viruses with inherent anti-cancer activity have been identified and are in different phases of clinical trials. In the era of modern biotechnology and with better understanding of cancer biology and virology, it has become feasible to engineer the oncolytic viruses (OVs) to increase their tumour selectivity and enhance their oncolytic activity. In this review, the mechanisms by which oncolytic viruses kill the tumour cells have been discussed as also the development made in virotherapy for cancer treatment with emphasis on their tumour specific targeting.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
6.
Viral genes as oncolytic agents for cancer therapy Gupta, Shishir Kumar; Gandham, Ravi Kumar; Sahoo, A. P ...
Cellular and molecular life sciences : CMLS,
03/2015, Letnik:
72, Številka:
6
Journal Article
Recenzirano
Many viruses have the ability to modulate the apoptosis, and to accomplish it; viruses encode proteins which specifically interact with the cellular signaling pathways. While some viruses encode ...proteins, which inhibit the apoptosis or death of the infected cells, there are viruses whose encoded proteins can kill the infected cells by multiple mechanisms, including apoptosis. A particular class of these viruses has specific gene(s) in their genomes which, upon ectopic expression, can kill the tumor cells selectively without affecting the normal cells. These genes and their encoded products have demonstrated great potential to be developed as novel anticancer therapeutic agents which can specifically target and kill the cancer cells leaving the normal cells unharmed. In this review, we will discuss about the viral genes having specific cancer cell killing properties, what is known about their functioning, signaling pathways and their therapeutic applications as anticancer agents.
To compare the effect of exercise regimens and medications on systolic blood pressure (SBP).
Medline (via PubMed) and the Cochrane Library.
Randomised controlled trials (RCTs) of ...angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-2 receptor blockers (ARBs), β-blockers, calcium channel blockers (CCBs) and diuretics were identified from existing Cochrane reviews. A previously published meta-analysis of exercise interventions was updated to identify recent RCTs that tested the SBP-lowering effects of endurance, dynamic resistance, isometric resistance, and combined endurance and resistance exercise interventions (up to September 2018).
Random-effects network meta-analysis.
Difference in mean change from baseline SBP between comparator treatments (change from baseline in one group minus that in the other group) and its 95% credible interval (95% CrI), measured in mmHg.
We included a total of 391 RCTs, 197 of which evaluated exercise interventions (10 461 participants) and 194 evaluated antihypertensive medications (29 281 participants). No RCTs compared directly exercise against medications. While all medication trials included hypertensive populations, only 56 exercise trials included hypertensive participants (≥140 mmHg), corresponding to 3508 individuals. In a 10% random sample, risk of bias was higher in exercise RCTs, primarily due to lack of blinding and incomplete outcome data. In analyses that combined all populations, antihypertensive medications achieved higher reductions in baseline SBP compared with exercise interventions (mean difference -3.96 mmHg, 95% CrI -5.02 to -2.91). Compared with control, all types of exercise (including combination of endurance and resistance) and all classes of antihypertensive medications were effective in lowering baseline SBP. Among hypertensive populations, there were no detectable differences in the SBP-lowering effects of ACE-I, ARB, β-blocker and diuretic medications when compared with endurance or dynamic resistance exercise. There was no detectable inconsistency between direct and indirect comparisons. Although there was evidence of small-study effects, this affected both medication and exercise trials.
The effect of exercise interventions on SBP remains under-studied, especially among hypertensive populations. Our findings confirm modest but consistent reductions in SBP in many studied exercise interventions across all populations but individuals receiving medications generally achieved greater reductions than those following structured exercise regimens. Assuming equally reliable estimates, the SBP-lowering effect of exercise among hypertensive populations appears similar to that of commonly used antihypertensive medications. Generalisability of these findings to real-world clinical settings should be further evaluated.
Many viral proteins exhibit selective cytotoxicity for tumor cells without affecting the normal diploid cells. The apoptin protein of chicken infectious anemia virus is one of such proteins, which ...has been shown to kill tumor cells specifically. However, an effective cancer treatment strategy also requires assistance from the immune system. Recently, poly (I:C) has been shown to be an effective cancer vaccine adjuvant.
In this study, we assessed the anti-tumor potential of apoptin gene transfer alone and in combination with poly (I:C) in a 4T1 mouse mammary tumor model.
4T1 cells were used to induce mammary tumor in Balb/c mice. Mice bearing tumors were divided into 6 groups, and each group received six intratumoral injections during a period of one month. After the last immunization, the animals were sacrificed, and peripheral blood, spleen, lungs, liver, heart, kidney and tumor tissues were collected for immunological, molecular and pathological analysis.
We report that intratumoral administration of apoptin plasmid along with poly (I:C) not only significantly inhibited the growth of mammary tumor, but also induced a potent anti-tumor immune response as indicated by the increase in blood CD4+, CD8+ cells and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed increased secretion of Th1 cytokines (IFN-γ and IL-2).
The results of our study demonstrate that the inclusion of poly (I:C) significantly enhanced the anti-tumor activity of apoptin mainly by inducing a potent anti-tumor immune response. Therefore, we report the use of apoptin and poly (I:C) combination as a novel and powerful strategy for cancer immunotherapy.
•We report that apoptin protein significantly inhibits growth of mammary tumor.•The combination of apoptin and poly (I:C) shows significantly enhanced oncolytic activity.•Poly (I:C) inclusion also enhances anti-tumor immune response significantly.•The immune response is polarized towards Th1 type.
Day-old broiler chicks (182) were distributed randomly to 7 treatments with 2 replicates. Treatments were T1 (control), basal diet; T2, basal diet + turmeric powder (TP) (0.5% of basal diet); T3, ...basal diet + TP (1% of basal diet); T4, basal diet + ginger powder (GP) (0.5% of basal diet); T5, basal diet + GP (1% of basal diet); T6, basal diet + TP + GP (0.5% TP + 0.5% GP); T7, basal diet + TP + GP (1% TP + 1.0% GP). The experiment was continued for 35 days. Immunity, antioxidant, liver enzyme activity, gut bacterial load and histopathology of broilers were conducted at fifth week of age. Higher cellular response against PHA-P was recorded in T3 and T7. Higher antibody titre against SRBC was recorded in T3. The weight of lymphoid organs did not differ significantly. Significantly higher erythrocyte malondialdehyde (MDA) level was recorded in T1. Significantly higher alanine amino transferase (ALT) levels were found in T1 and T7. Significantly higher aspartate amino transferase (AST) level was found in T1. Higher total bacterial count and lower E. coli count were recorded in group T3 and lower total bacterial count was recorded in T7. In group T1, liver showed mild congestion to mild cellular swelling and varying degree of vacuolar degeneration. From this study, it may be concluded that supplementation of 1% turmeric in ration either alone or in combination with 1% ginger improved the immunity, antioxidant status and gut health of broilers.
Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and ...found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes.
We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest.
From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths.
The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development.
Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.
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