Toll-like receptor 13-mediated signaling protects against the development of colon cancer.

Appropriate host-microbiota interactions are essential for maintaining intestinal homeostasis; hence, an imbalance in these interactions leads to inflammation-associated intestinal diseases. Toll-like receptors (TLRs) recognize microbial ligands and play a key role in host-microbe interactions in health and disease. TLR13 has a well-established function in enhancing host defenses against pathogenic bacteria. However, its role in maintaining intestinal homeostasis and controlling colitis-associated colon cancer (CAC) is largely unknown. This study aimed to investigate the involvement of TLR13-mediated signaling in intestinal homeostasis and colonic tumorigenesis using ex vivo cell and in vivo CAC animal model. Tlr13-deficient mice were prone to dextran sodium sulfate (DSS)-induced colitis. During the early stages of the CAC regimen (AOM/DSS-treated), Tlr13 deficiency led to severe ulcerative colitis. Moreover, Tlr13-deficient mice exhibited increased intestinal permeability, as evidenced by elevated levels of fluorescein isothiocyanate (FITC)-dextran, endotoxins, and bacterial translocation. Enhanced cell survival and proliferation of colonic intestinal cells were observed in Tlr13-deficient mice. A transcriptome analysis revealed that Tlr13 deficiency is associated with substantial changes in gene expression profile of colonic tumor tissue. Tlr13-deficient mice were more susceptible to CAC, with increased production of interleukin (IL)-6, IL-12, and TNF-α cytokines and enhanced STAT3, NF-κB, and MAPK signaling in colon tissues. These findings suggest that TLR13 plays a protective role in maintaining intestinal homeostasis and controlling CAC. Our study provides a novel perspective on intestinal health via TLR13-mediated signaling, which is crucial for deciphering the role of host-microbiota interactions in health and disease.

Diesel exhaust particulate matter impairs Toll-like receptor signaling and host defense against staphylococcal cutaneous infection in mice.

Air pollution is an emerging cause of mortality, affecting nearly 5 million people each year. Exposure to diesel exhaust fine particulate matter (PM2.5) aggravates respiratory and skin conditions. However, its impact on the protective immunity of the skin remains poorly understood. This study aimed to investigate the underlying molecular mechanism for adverse effects of PM2.5 on the host protective immunity using in vitro cell and in vivo mouse model. Intracellular translocation of Toll-like receptor 9 (TLR9) and CpG-DNA internalization were assessed in dendritic cells without or with PM2.5 treatment using immunofluorescence staining. Cytokine and nitric oxide production were measured in dendritic cells and macrophages without or with PM2.5 treatment. NF-κB and MAPK signaling was determined using western blotting. Skin disease severity, bacterial loads, and cytokine production were assessed in cutaneous Staphylococcus aureus (S. aureus) infection mouse model. PM2.5 interfered with TLR9 activation by inhibiting both TLR9 trafficking to early endosomes and CpG-DNA internalization via clathrin-mediated endocytosis. In addition, exposure to PM2.5 inhibited various TLR-mediated nitric oxide and cytokine production as well as MAPK and NF-κB signaling. PM2.5 rendered mice more susceptible to staphylococcal skin infections. Our results suggest that exposure to PM impairs TLR signaling and dampens the host defense against staphylococcal skin infections. Our data provide a novel perspective into the impact of PM on protective immunity which is paramount to revealing air pollutant-mediated toxicity on the host immunity.

Production of Sitobion avenae-resistant Triticum aestivum cvs using laccase as RNAi target and its systemic movement in wheat post dsRNA spray.

Among the wheat biotic stresses, Sitobion avenae is one of the main factors devastating the wheat yield per hectare. The study's objective was to find out the laccase (lac) efficacy; as a potential RNAi target against grain aphids. The Sitobion avenae lac (Salac) was confirmed by Reverse Transcriptase-PCR. Gene was sequenced and accession number "ON703252" was allotted by GenBank. ERNAi tool was used to design 143 siRNA and one dsRNA target. 69% mortality and 61% reduction in lac expression were observed 8D-post lac DsRNA feeding. Phylogenetic analysis displayed the homology of grain aphid lac gene with peach potato, pea, and Russian wheat aphids. While Salac protein was found similar to the Russian grain, soybean, pea, and cedar bark aphid lac protein multi-copper oxidase. The dsRNAlac spray-induced silencing shows systematic translocation from leaf to root; with maximum lac expression found in the root, followed by stem and leaf 9-13D post-spray; comparison to control. RNAi-GG provides the Golden Gate cloning strategy with a single restriction ligation reaction used to achieve lac silencing. Agrobacterium tumefaciens mediated in planta and in-vitro transformation was used in the study. In vitro transformation, Galaxy 2012 yielded a maximum transformation efficiency (1.5%), followed by Anaj 2017 (0.8%), and Punjab (0.2%). In planta transformation provides better transformation efficiencies with a maximum in Galaxy 2012 (16%), and a minimum for Punjab (5%). Maximum transformation efficiency was achieved for all cultivars with 250 µM acetosyringone and 3h co-cultivation. Galaxy 2012 exhibited maximum transformation efficiency, and aphid mortality post-feeding transgenic wheat.

A Review on Nuclear Imaging as a Promising Modality for Efficient Diagnosis of Tuberculosis.

Tuberculosis (TB) is an infectious disease, which has been declared as a global health issue by the World Health Organization in 1993. Due to the complex pathophysiology of Mycobacterium tuberculosis, it remains a global threat. This article reviews the conventional diagnostic modalities for tuberculosis, their limitations to detect latent TB, multiple drug resistant-TB, human immunodeficiency virus co-infected TB lesions, and TB in children. Moreover, this review illustrates the importance of nuclear medicine imaging for early, non-invasive diagnosis of TB, to detect disease stages and to monitor therapy response. Single-photon emission computed tomography and positron emission tomography with their particular radionuclides are now extensively being used for a thorough assessment of TB.

The Established Nuclear Medicine Modalities for Imaging of Bone Metastases.

BACKGROUND: The skeleton is one of the frequent site of metastases in advanced cancer. Prostate, breast and renal cancers mostly metastasize to bone. DISCUSSION: Malignant tumors lead to significant morbidity and mortality. Identification of bone lesions is a crucial step in diagnosis of disease at early stage, monitoring of disease progression and evaluation of therapy. Diagnosis of cancer metastases is based on uptake of bone-targeted radioactive tracer at different bone remodeling sites. CONCLUSION: This manuscript summarizes already established and evolving nuclear medicine modalities (e.g. bone scan, SPECT, SPECT/CT, PET, PET/CT) for imaging of bone metastases.

Gynaecological Cancer Diagnostics: 99mTc-Cisplatin Complex as a Future Approach for Early, Prompt and Efficient Diagnosis of Gynaecological Cancer.

BACKGROUND: Gynaecological cancers (GCCa) are common and have a significant mortality rate all over the world. Early diagnosis of cancer can play a key role in the treatment and survival of a patient. Identification, staging, treatment, and monitoring of gynaecological malignancies is being done successfully by nuclear medicines. DISCUSSION: Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) centered imaging techniques are being developed for use in patients with GCCa as a diagnostic tool. The present work elucidates several clinical studies on the use of radiopharmaceuticals, based on their effectiveness, in the early detection and management of GCCa. It also highlights the importance of reconsidering the biology for nuclear imaging as a future modality for early, rapid and efficient diagnosis of gynecological cancers. This comprehensive review is a part of our study designed to detect gynaecological cancers at an early stage using radionuclide complex, 99m Tc-Cisplatin. CONCLUSION: This article summarizes the significance of radioscintigraphy such as single-photon emission computed tomography (SPECT) and PET for identification of GCCa in the experimental humans and animals.