Impact of Lysinibacillus macroides, a potential plant growth promoting rhizobacteria on growth, yield and nutritional value of tomato Plant (Solanum lycopersicum L. f1 hybrid Sachriya)

Plant growth promoting bacteria enhance the growth in plants by solubilizing insoluble minerals, producing phytohormones and by secreting enzymes that resist pathogen attack. The present study was aimed at identifying the potential of Lysinibacillus macroides isolated from pea plant possessing rich microbial rhizobiome diversity in promoting the growth of tomato plant (Solanum lycopersicum L). Potential of L. macroides in the promotion of S. lycopersicum L. growth by increased shoot length, terminal leaf length and breadth was assessed. Anatomical sectioning of stem and root revealed no varied cellular pattern indicating that the supplemented bioculture is not toxic to S. lycopersicum. Plantlets treated with L. macroides along with organic compost showed an increased total phenol content (17.58±0.4 mg/g) compared to control samples (12.44±0.41 mg/g). Carbohydrate content was noticed to be around 1.3 folds higher in the L. macroides plus compost mixture supplemented slots compared to control sample. Significant increase in shoot length was evident in the L. macroides plus compost supplied slots (23.4±2.7 cm). Plant growth promoting properties might be due to the nitrogen fixing activity of the bacteria which enrich the soil composition along with the nutrients supplied by the organic compost. Rich microbial rhizobiome diversity in pea plant and the usage of L. macroides from a non-conventional source improves the diversity of the available PGPR for agricultural practices. Further research is needed to detect the mechanism of growth promotion and to explore the plant microbe interaction pathway

Cosmetovigilance: knowledge, attitude and practice study

Background: Adverse reactions due to cosmetics should be reported to avoid similar incidences and is highly required to evaluate the risks and benefits of ingredients used in cosmetics. Methods: This study is to evaluate the knowledge, attitude, and practice of cosmetovigilance among PGs, interns, and consumers of cosmetics. This was a cross-sectional questionnaire- based study conducted among 180 participants of SSMC Tumkur, Karnataka, in India for a period of 1 month. Results: The Results obtained were analysed using descriptive statistics.: About 46.1% of the participants were aware about the concept of cosmetovigilance. Only an average of about 5% of participants practiced this concept but the attitude towards this concept was satisfactory. Conclusions: Overall the participants had a less satisfactory overview of this concept and hence educational interventions can aid in serving the purpose especially among medical students

The Fetal Basis of Amyloidogenesis: Exposure to Lead and Latent Overexpression of Amyloid Precursor Protein and β-Amyloid in the Aging Brain

The fetal basis of adult disease (FeBAD) hypothesis states that many adult diseases have a fetal origin. According to FeBAD, injury or environmental influences occurring at critical periods of organ development could result in “programmatic” changes via alterations in gene expression or gene imprinting that may result in functional deficits that become apparent later in life. Alzheimer\u27s disease (AD) is a progressive neurodegenerative disorder that is characterized by excessive deposits of aggregated β-amyloid (Aβ) peptides, which are snippets of the β-amyloid precursor protein (APP). The predominately sporadic nature of AD suggests that the environment must play a role in neurodegeneration. To examine latent responses to an environmental agent, we exposed rodents to lead and monitored the lifetime expression of the APP gene. We observed that APP mRNA expression was transiently induced in neonates, but exhibited a delayed overexpression 20 months after exposure to Pb had ceased. This upregulation in APP mRNA expression was commensurate with a rise in activity of the transcription factor Sp1, one of the regulators of the APP gene. Furthermore, the increase in APP gene expression in old age was accompanied by an elevation in APP and its amyloidogenic Aβ product. In contrast, APP expression, Sp1 activity, as well as APP and Aβ protein levels were unresponsive to Pb exposure during old age. These data suggested that environmental influences occurring during brain development predetermined the expression and regulation of APP later in life, potentially altering the course of amyloidogenesis

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transciption Factors

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. Results: The IC50 value for Cu-TA was about half than TA. Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. Conclusion: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth

Lifespan profiles of Alzheimer's disease–associated genes and their products in monkeys and mice.

Alzheimer's disease (AD) is characterized by plaques of amyloid–beta (Aβ) peptide, cleaved from amyloid–β precursor protein (AβPP). Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice, and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AβPP mRNA, AβPP protein, and Aβ levels in rodents and primates. We also tracked a transcriptional regulator of the AβPP gene, specificity protein 1 (SP1), and the β amyloid precursor cleaving enzyme (BACE1). In mice, AβPP and Sp1 mRNA and their protein products were elevated late in life; Aβ levels declined in old age. In monkeys, Sp1, AβPP, and BACE1 mRNA declined in old age, while protein products and Aβ levels rose. Proteolytic processing in both species did not match production of Aβ. In primates, AβPP and Sp1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products, as well as Aβ levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age–related diseases

Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog

OBJECTIVE: To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification. DESIGN: Secondary analysis of data in the Polygenic Score Catalog. SETTING: Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification. PARTICIPANTS: Individuals contributing to the published studies in the Polygenic Score Catalog. MAIN OUTCOME MEASURES: Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples. RESULTS: For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases. CONCLUSION: Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance

Alzheimer\u27s Disease (AD)-Like Pathology in Aged Monkeys after Infantile Exposure to Environmental Metal Lead (Pb): Evidence for a Developmental Origin and Environmental Link for AD

The sporadic nature of Alzheimer\u27s disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic β-amyloid (Aβ) product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 (β-site APP cleaving enzyme 1)] as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Aβ staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD

Lead (Pb) exposure and its effect on APP proteolysis and Abeta aggregation

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with clinical manifestations appearing in old age, however, the initial stages of this disease may begin early in life. AD is characterized by the presence of excessive deposits of aggregated beta-amyloid (Abeta) peptides, which are derived from the beta-amyloid precursor protein (APP) following processing by beta-secretase and gamma-secretase. Recently, we have reported that developmental exposure of rats to Pb resulted in latent elevation of APP mRNA, APP, and Abeta in old age. Here we examined whether latent up-regulation in APP expression and Abeta levels is exacerbated by concurrent disturbances in APP processing or Abeta aggregation. Among the environmental metals tested, only Abeta solutions containing Pb promoted the formation of Abeta aggregates at nanomolar concentrations. The lifetime profiles of alpha-, beta-, and gamma-secretases remained constant in adult and aging animals, and developmental exposure to Pb did not alter them. Furthermore, the addition of various concentrations of Pb (0.1 to 50 microM) to cerebral cortical extracts derived from control animals also did not affect the proteolytic activities of these enzymes. Therefore, we propose that amyloidogenesis is promoted by a latent response to developmental reprogramming of the expression of the APP gene by early exposure to Pb, as well as enhancement of Abeta aggregation in old age. In rodents, these events occur without Pb-induced disturbances to the enzymatic processing of APP. The aforementioned results provide further evidence for the developmental basis of amyloidogenesis and late-life disturbances in AD-associated proteins by environmental agents

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. Results: The IC50 value for Cu-TA was about half than TA.Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. Conclusion: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth