Nixonparrott1272

Liver cancer is a critical clinical condition with augmented malignancy, rapid progression, and poor prognosis. Liver cancer often initiates as fibrosis, develops as cirrhosis, and results in cancer. For centuries, medicinal plants have been incorporated in various liver-associated complications, and recently, research has recognized that many bioactive compounds from medicinal plants may interact with targets related to liver disorders. Phyllanthin from the Phyllanthus species is one such compound extensively used by folklore practitioners for various health benefits. However, most practices continue to be unrecognized scientifically. Hence, in this work, we investigated the protective role of phyllanthin on diethylnitrosamine (DEN) induced liver carcinoma in Wistar Albino rats and the anti-tumor potential on human hepatocellular carcinoma (HCC) HepG2 cells. The DEN-challenged liver cancer in experimental rats caused increased liver weight, 8-OHD, hepatic tissue injury marker, lipid peroxidation, and tumor markers levels. Remarkably, phyllanthin counteracted the DEN effect by ameliorating all the liver function enzymes, oxidative DNA damage, and tumor-specific markers by enhanced anti-oxidant capacity and induced caspase-dependent apoptosis through the mTOR/ PI3K signaling pathway. MTT assay demonstrated that phyllanthin inhibited the HepG2 cell growth in a dose-dependent manner. Fascinatingly, phyllanthin did not demonstrate any substantial effect on the normal cell line, HL7702. In addition, HepG2 cells were found in the late apoptotic stage upon treatment with phyllanthin as depicted by acridine orange/ethidium bromide staining. Overall, this work offers scientific justification that phyllanthin can be claimed to be a safe candidate with potential chemotherapeutic activity against HCC.Arsenic (As) contamination is a well-recognized environmental and health issue, threatening over 200 million people worldwide with the prime cases in South and Southeast Asian and Latin American countries. Rice is mostly cultivated under flooded paddy soil conditions, where As speciation and accumulation by rice plants is controlled by various geo-environmental (biotic and abiotic) factors. In contrast to other food crops, As uptake in rice has been found to be substantially higher due to the prevalence of highly mobile and toxic As species, arsenite (As(III)), under paddy soil conditions. Selleckchem Remodelin In this review, we discussed the biogeochemical cycling of As in paddy soil-rice system, described the influence of critical factors such as pH, iron oxides, organic matter, microbial species, and pathways affecting As transformation and accumulation by rice. Moreover, we elucidated As interaction with organic and inorganic amendments and mineral nutrients. The review also elaborates on As (im)mobilization processes and As uptake by rice under the influence of different mineral nutrients and amendments in paddy soil conditions, as well as their role in mitigating As transfer to rice grain. This review article provides critical information on As contamination in paddy soil-rice system, which is important to develop suitable strategies and mitigation programs for limiting As exposure via rice crop, and meet the UN's key Sustainable Development Goals (SDGs 2 (zero hunger), 3 (good health and well-being), 12 (responsible consumption and production), and 13 (climate action)).Pathogen-specific immunity evolves in the context of the infected tissue. However, current immune correlates analyses and vaccine efficacy metrics are based on immune functions from peripheral cells. Less is known about tissue-resident mechanisms of immunity. While antibodies represent the primary correlate of immunity following most clinically approved vaccines, how antibodies interact with localized, compartment-specific immune functions to fight infections, remains unclear. Emerging data demonstrate a unique community of immune cells that reside within different tissues. These tissue-specific immunological communities enable antibodies to direct both expected and unexpected local attack strategies to control, disrupt, and eliminate infection in a tissue-specific manner. Defining the full breadth of antibody effector functions, how they selectively contribute to control at the site of infection may provide clues for the design of next-generation vaccines able to direct the control, elimination, and prevention of compartment specific diseases of both infectious and non-infectious etiologies.

Schizophrenia (SZ) is a severe mental disease with highly heterogeneous clinical manifestations and pathological mechanisms. Schizophrenia is linked to abnormalities in cell membrane phospholipids and blunting of the niacin skin flush response, but the associations between these phenotypes and its molecular pathogenesis remain unclear. This study aimed to describe the PLA2/COX pathway, the key link between phospholipids and niacin flush, and to illustrate the pathogenic mechanisms in schizophrenia that mediate the above phenotypes.

A total of 166 patients with schizophrenia and 54 healthy controls were recruited in this study and assigned to a discovery set and a validation set. We assessed the mRNA levels of 19 genes related to the PLA2/COX cascade in leukocytes by real-time PCR. Plasma IL-6 levels were measured with an ELISA kit. Genetic association analysis was performed on PLA2G4A and PTGS2 to investigate their potential relationship with blunted niacin-skin response in an independent sample set.

Sial Science and Technology Major Project (2017SHZDZX01); China Postdoctoral Science Foundation (2018M642029, 2018M630442, 2019M661526, 2020T130407); Natural Science Foundation of Shanghai (20ZR1426700); and Startup Fund for Youngman Research at SJTU (19 × 100040033).

Oncolytic virotherapy with vaccinia virus (VV) can lead to effective anti-tumor immunity by turning "cold" tumors into "hot" tumors. However, its therapeutic potential is affected by the tumor's local immunosuppressive tumor microenvironment (TME). Therefore, it is necessary to explore the use of immune checkpoint inhibitors to arm oncolytic VVs to enhance their anti-tumor efficacy.

A novel recombinant oncolytic VV, VV-α-TIGIT, which encoded a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT) was generated by homologous recombination with a shuttle plasmid. The anti-tumor efficacy of the VV-α-TIGIT was investigated in several subcutaneous and ascites tumor models.

The functional α-TIGIT was sufficiently produced and secreted by tumor cells infected with VV-α-TIGIT, which effectively replicated in tumor cells leading to significant oncolysis. Intratumoral injection of VV-α-TIGIT improved anti-tumor efficacy in several murine subcutaneous tumor models compared to VV-Control (without α-TIGIT insertion).