Gene expression is a fundamental mechanism in susceptibility to and manifestation of complex disease. We performed transcriptome analysis and weighted gene co-expression network analysis in late onset Alzheimer's disease (LOAD) using microarray gene expression profiles from the Alzheimer's Disease Neuroimaging Initiative (ADNI). 715 ADNI participants with Affymetrix Human Genome U219 Array data from peripheral blood samples (PaxGene RNA tubes) were included. Raw expression values were pre-processed using the Robust Multi-chip Average normalization followed by standard quality control (QC) procedures on samples and probe sets. Statistical analysis of microarray data was performed using the regularized t-test to evaluate differences in gene expression between AD and cognitively normal controls (HC), weighted gene co-expression network analysis to identify clusters of highly correlated genes, and MetaCore to perform a gene-set enrichment analysis. Data were adjusted for age, gender, plate, four principal components from multidimensional scaling, and RIN score (RNA integrity number). Significant associations were determined using FDR adjustment for multiple testing. Of the 18,866 probe sets represented on the array after QC, 27 probe sets (23 genes) were significantly up-regulated and 15 probe sets (15 genes) were significantly down-regulated in LOAD after controlling for multiple testing (corrected p<0.05) (Fig. 1). The most significantly altered gene was MAPK14 (up-regulated; corrected p=0.0087; Fig. 2). Network analysis identified two modules associated with diagnosis. The modules consisted of altered genes involved in immune response and mitochondrial processes, respectively (Fig. 3). RNA from peripheral blood indicated a differential gene expression pattern between AD patients and controls. MAPK14 critically regulates the immunological response in astrocytes (Selvaraj et al. 2014). Peripheral blood cells have been shown to share significant gene expression similarities with multiple central nervous system tissues, sharing more than 80% of the transcriptome with brain tissues (Liew et al. 2006). Gene expression signature in peripheral blood is a promising and accessible marker that can reveal novel cellular and molecular mechanisms that may contribute to LOAD.
Breakpoints provided by European Committee on Antimicrobial Susceptibility Testing (EUCAST) are now being used in many countries. This study was planned to ascertain the agreement in antimicrobial susceptibility using the Clinical and Laboratory Standards Institute (CLSI) and EUCAST breakpoints during the Kirby-Bauer disk diffusion method. This was a prospective observational study. Clinical isolates belonging to the family Enterobacteriaceae recovered between January and December, 2022, were included in the analysis. The diameter of the zone of inhibition of the 14 antimicrobials (viz. amoxicillin/clavulanic acid, cefazolin, ceftriaxone, cefuroxime, cefixime, aztreonam, meropenem, gentamicin, amikacin, ciprofloxacin, levofloxacin, norfloxacin, trimethoprim/sulfamethoxazole and fosfomycin) was analysed. Antimicrobial susceptibility was interpreted using CLSI 2022 and EUCAST 2022 guidelines. Results: Susceptibility data from a total of 356 isolates showed a slight increase in the percentage of resistant isolates with most of the drugs using EUCAST guidelines. The level of agreement varied from almost perfect to slight. For two drugs, i.e., fosfomycin and cefazolin, the agreement was least among the drug analysed (kappa (κ) value < 0.5, p < 0.001). For Ceftriaxone and Aztreonam, with EUCAST, susceptible (S) isolates would have been categorised in the newly redefined "I" category. It would have indicated the use of higher dosages of drugs. Conclusion: Change in the breakpoints impacts the interpretation of the susceptibility. It can also lead to a change in the dosage of the drug used for treatment. Therefore, there is an urgent need to see the impact of recent modifications "I" category of EUCAST on the clinical outcome and usage of antimicrobials.
This pioneering study aims to address the paradox of the highly regarded Kinnow mandarin fruit, whose valuable peels have been considered undesired remnants from industrial fruit juice production. The study proposes the utilization of these discarded peels to synthesize ecologically safe gold nanoparticles (K-AuNPs) through a one-pot method. The objectives of this research are to synthesize K-AuNPs using an ecologically safe single-step approach, utilizing discarded Kinnow mandarin fruit peels, and to assess their antibacterial and antidiabetic potential. The validation of K-AuNPs involved various techniques including UV-visible spectroscopy, TEM, DLS, and zeta-potential investigations. The antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis was compared to levofloxacin and Kinnow mandarin aqueous peel extract (KAPE). Furthermore, the anti-diabetic efficacy was evaluated through α-amylase and α-glucosidase experiments, comparing K-AuNPs to pure KAPE and the standard inhibitor acarbose. The results confirmed the successful synthesis of K-AuNPs from KAPE, as evidenced by UV-spectral profiles (527 nm), TEM micrographs (∼21 d. nm), dynamic light scattering (65 d.nm), and zeta-potential (-12 mV). The K-AuNPs demonstrated a superior zone of inhibition and lower MIC values against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis, surpassing levofloxacin and KAPE alone. Additionally, the K-AuNPs exhibited potent anti-diabetic efficacy, outperforming both pure KAPE and acarbose at a lower dosage. To sum up, the process of producing K-AuNPs utilizing Kinnow mandarin peel extracts demonstrates a powerful antibacterial and antidiabetic remedy sourced from previously discarded materials. These findings signify a significant leap forward in the domain of natural product exploration, with the potential to fundamentally reshape modern healthcare approaches.
Abstract Although T cells infiltrate many types of murine and human neoplasms, in many instances tumor-specific cytotoxicity is not observed. Strategies to stimulate CTL-mediated antitumor immunity have included in vitro stimulation and/or genetic engineering of T cells, followed by adoptive transfer into tumor-bearing hosts. In this model of B cell lymphoma in SJL/J mice, we used Tim-3+ T-bet+ Th1 cells to facilitate the development of tumor-specific CTL. Tumor-specific Th1 cell lines were polarized with IL-12 during in vitro stimulation and long term maintenance. As few as 5 million Tim-3+ T-bet+ Th1 cells enabled recipients to resist growth of malignant transplantable cells. In addition, similar numbers of Th1 cells injected into 2- to 3-mo-old mice inhibited development of the spontaneous primary lymphomas, which normally arise in 90% of aging mice. CFSE+ Th1 cells colocalized with injected tumor cells in vivo and formed conjugates with the tumor cells within follicles, whereas in nontumor-challenged recipients the CFSE+ Th1 cells localized only within the T cell zones of the spleen. These results provide evidence that adoptive immunotherapy with Tim-3+ T-bet+ tumor-specific Th1 cells can be used to induce host cytotoxic responses that inhibit the development and growth of neoplastic cells.
In the current scenario, it is an urgent requirement to satisfy the nutritional demands of the rapidly growing global population. Using conventional farming, nearly one third of crops get damaged, mainly due to pest infestation, microbial attacks, natural disasters, poor soil quality, and lesser nutrient availability. More innovative technologies are immediately required to overcome these issues. In this regard, nanotechnology has contributed to the agrotechnological revolution that has imminent potential to reform the resilient agricultural system while promising food security. Therefore, nanoparticles are becoming a new-age material to transform modern agricultural practices. The variety of nanoparticle-based formulations, including nano-sized pesticides, herbicides, fungicides, fertilizers, and sensors, have been widely investigated for plant health management and soil improvement. In-depth understanding of plant and nanomaterial interactions opens new avenues toward improving crop practices through increased properties such as disease resistance, crop yield, and nutrient utilization. In this review, we highlight the critical points to address current nanotechnology-based agricultural research that could benefit productivity and food security in future.
Mammary gland growth and differentiation predominantly rely on stromal-epithelial cellular communication. Specifically, mammary adipocytes play a crucial role in ductal morphogenesis, as well as in the proliferation and differentiation of mammary epithelial cells. The process of lactation entails a reduction in the levels of white adipose tissue associated with the MG, allowing for the expansion of milk-producing epithelial cells. Subsequently, during involution and the regression of the milk-producing unit, adipocyte layers resurface, occupying the vacated space. This dynamic phenomenon underscores the remarkable plasticity and expansion of adipose tissue. Traditionally considered terminally differentiated, adipocytes have recently been found to exhibit plasticity in certain contexts. Unraveling the significance of this cell type within the MG could pave the way for novel approaches to reduce the risk of breast cancer and enhance lactation performance. Moreover, a comprehensive understanding of adipocyte trans- and de-differentiation processes holds promise for the development of innovative therapeutic interventions targeting cancer, fibrosis, obesity, type 2 diabetes, and other related diseases. Additionally, adipocytes may find utility in the realm of regenerative medicine. This review article provides a comprehensive examination of recent advancements in our understanding of MG remodelling, with a specific focus on the tissue-specific functions of adipocytes and their role in the development of cancer. By synthesizing current knowledge in this field, it aims to consolidate our understanding of adipocyte biology within the context of mammary gland biology, thereby fostering further research and discovery in this vital area.
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