Acetaminophen (APAP, 4-hydroxyacetanilide) is the most common cause of acute liver failure in the United States. In addition to exhibiting hepatotoxicity, APAP exerts a nephrotoxic effect may be independent of the induced liver damage. Toll-like receptors (TLRs) have been suggested as a potential class of novel therapeutic targets. The aim of the present study was to investigate the potential of the TLR-4 blocker TAK-242 in the prevention of APAP-induced hepato-renal failure. Four groups of C57BL mice were studied: Vehicle-treated/control (VEH), APAP-treated (APAP), N-acetyl cysteine (NAC)-pretreated plus APAP (APAP + NAC) and TAK-242-pretreated plus APAP (APAP + TAK) groups. Mice were clinically assessed then perfused 4 h later. Liver and kidney tissues were collected and examined histologically using basic hematoxylin and eosin staining to detect signs of necrosis and inflammation. Plasma samples were collected to measure the levels of alanine transaminase, aspartate transaminase and serum creatinine. In addition, liver and kidney tissues were assayed to determine the levels of reduced glutathione. The results of the present study indicate the potential role of TLR-4 in APAP-induced organ toxicity. In the APAP + TAK and APAP + NAC groups, histopathological examination indicated that pretreatment with TAK-242 or NAC afforded protection against APAP-induced injury. However, this protective effect was more clinically evident in the APAP + TAK group compared with the APAP + NAC group. The various biochemical parameters (serum enzymes and reduced glutathione) revealed no significant protection in either of the pretreated groups. Therefore, the present study indicated that the TLR-4 blocker had protective effects against acute APAP toxicity in liver and kidney tissues. These effects were identified clinically, histologically and biochemically. Furthermore, the TLR-4 blocker TAK-242 exhibited antioxidant properties in addition to anti-inflammatory effects.
Background: Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation. Methods: In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of several types of cancer including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, hodgkin lymphoma, cervical cancer, head and neck squamous cell carcinoma. Results: Based on the last updated list released on March 2019, seven ICIs are approved by the FDA including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab. Conclusion: This review also highlighted the most common adverse effects caused by ICIs and which affect people in different ways.
Genetic variability, correlation and path coefficient were studied for yield and yield component traits in twenty one diverse genotypes of pumpkin. Highest genotypic coefficient of variation was recorded for fruit length (cm), single fruit weight (kg), Brix (%) and yield per plant (kg). Heritability estimates in broad sense were higher for almost all the characters. The characters namely, fruit length, single fruit weight, yield per plant and brix% had high genotypic coefficient of variation coupled with heritability gave high genetic advance expressed as percentage of mean ranged from 76.84 to 96.06 which indicated that these characters were less influenced by environment confirming additive gene action, and therefore, selection of these characters would be more effective for yield improvement of pumpkins. Total six traits likely fruit length, fruit diameter, flesh thickness, single fruit weight and number of fruits per plant were positively and significantly associated with yield per plant. Path coefficient analysis also revealed maximum contribution of single fruit weight (0.869) to yield and this was followed by the contribution of number of fruit per plant (0.527) at genotypic level.
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.
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