Notes

Subclinical thyrois issues is individually connected with poor kidney outcomes inside individuals along with persistent elimination condition.
A copper-catalyzed mono-selective C-H amination of ferrocenes assisted by 8-aminoquinoline is presented here. A range of amines, including bioactive molecules, were successfully installed to the ortho-position of ferrocene amides with high efficiency under mild conditions. A range of functionalized ferrocenes were compatible to give the aminated products in moderate to good yields. The gram-scale reaction was smoothly conducted and the directing group could be removed easily under basic conditions.Cold-tolerant bacteria are known to contaminate and cause defects in refrigerated foods. Defects in food products can be observed as changes in appearance, texture, and/or flavor that detract from the product's intended look, feel, or taste. Two distinct organisms were cultured from blue pigmented soymilk and tofu that had been left opened and expired in a home refrigerator. The blue coloration was reproduced when isolates were cultured in fresh, sterile soymilk. These strains also produced a variety of colony color morphologies when cultured on different media types. We report two draft genome sequences of the potential causative agents of blue discoloration of soy foods, Pseudomonas carnis strains UCD_MED3 and UCD_MED7 as well as the 16S rRNA gene sequences of co-occurring strains isolated from the defective soy samples but that did not cause blue discoloration when cultured in fresh soymilk; Serratia liquefaciens strains UCD_MED2 and UCD_MED5.Pathogenic variants (PVs) in BRCA genes have been mainly associated with an increasing risk of triple negative breast cancer (TNBC). The contribution of PVs in non-BRCA genes to TNBC seems likely since the processing of homologous recombination repair of double-strand DNA breaks involves several genes. Here, we investigate the susceptibility of genetic variation of the BRCA and non-BRCA genes in 30 early-onset Moroccan women with TNBC. Methods Targeted capture-based next generation sequencing (NGS) method was performed with a multigene panel testing (MGPT) for variant screening. Panel sequencing was performed with genes involved in hereditary predisposition to cancer and candidate genes whose involvement remains unclear using Illumina MiSeq platform. Interpretation was conducted by following the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) criteria. Results PVs were identified in 20% (6/30) of patients with TNBC. Of these, 16.7% (5/30) carried a BRCA PV [10%ith BRCA genetic screening could be helpful for a larger proportion of early-onset TNBC in Morocco.Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival. Methods We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features. Results We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells in vitro and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis. Conclusion Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.Background Glioblastoma (GBM) is one of the most aggressive types of brain cancer. GBM progression is closely associated with microglia activation; therefore, understanding the regulation of the crosstalk between human GBM and microglia may help develop effective therapeutic strategies. Elucidation of efficient delivery of microRNA (miRNA) via extracellular vesicles (EVs) and their intracellular communications is required for therapeutic applications in GBM treatment. Methods We used human GBM cells (U373MG) and human microglia. MiRNA-124 was loaded into HEK293T-derived EVs (miR-124 EVs). Various anti-tumor effects (proliferation, metastasis, chemosensitivity, M1/M2 microglial polarization, and cytokine profile) were investigated in U373MG and microglia. Anti-tumor effect of miR-124 EVs was also investigated in five different patient-derived GBM cell lines (SNU-201, SNU-466, SNU-489, SNU-626, and SNU-1105). A three-dimensional (3D) microfluidic device was used to investigate the interactive microenvironment ovide new insights toward a better understanding of the GBM microenvironment and provide substantial evidence for the development of potential therapeutic strategies using miRNA-loaded EVs.The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME. Methods Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs in vitro and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics. In vivo patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs. Results The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity in vitro and in vivo, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs. Conclusions The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.Background Monotherapy for cancer treatment is limited by unstable efficacy and uncontrollable toxic side effects, while the multifunctional nanoplatform with complex preparation process cannot avoid the potential toxicity of each functional component. Methods We exploited tumor-specific activated polyamino acid calcified nanoparticles (CHC NPs) as new-type oxidative stress amplification of anticancer drugs via building a safe and biodegradable multifunctional nanoplatform. Giving priority to chemotherapy, and synergizing chemodynamic therapy (CDT) with photodynamic therapy (PDT), this strategy was to achieve enhanced chemotherapy, simultaneously inducing immunogenic cell death and inhibiting tumor cell invasion. Results Based on amorphous calcium carbonate, pH-responsive nanocarrier was prepared with classical chemotherapeutic drug 10-hydroxycamplothecin (HCPT) and photosensitizer Chlorin e6 (Ce6) to realize multifunctional nanotheranostics. Conclusion Inventive calcified nanohybrids, where topoisomerase inhibited by HCPT to prevent DNA synthesis, the generation of •OH induced via Fenton reaction, along with a large amount of 1O2 produced by Ce6, might be a promising strategy for anti-tumor combination therapy in clinical translation.Microglia are the primary cellular source of type I interferons (I-IFNs) in the brain upon neurotropic virus infection. Although the I-IFN-based antiviral innate immune response is crucial for eliminating viruses, overproduction led to immune disorders. Therefore, the relatively long-lasting I-IFNs must be precisely controlled, but the regulatory mechanism for the innate antiviral response in microglia remains largely unknown. Long non-coding RNAs (lncRNAs) are being recognized as crucial factors in numerous diseases, but their regulatory roles in the innate antiviral response in microglia are undefined. Methods The high-throughput RNA sequencing was performed to obtain differentially expressed lncRNAs (DELs) in primary microglia infected with or without the neurotropic herpes simplex virus type 1 (HSV-1). We selected four DELs ranked in the top 15 in basic level and their fold change induced by HSV-1, i.e., FPKMHSV-1/FPKMCells.We subsequently found a key lncRNA affecting the innate antiviral response of micr I-IFN production through facilitating TBK1 degradation and limits the microglial innate immune response against neurotropic herpesvirus infection. Microglia-specific KI of linc-AhRA mice shows a weakened antiviral immune response upon neurotropic herpesvirus challenge due to a reduction of TBK1 in microglia. Conclusion Our findings indicate that linc-AhRA is a negative regulator of I-IFN production in microglia to avoid excessive autoimmune responses. These findings uncover a previously unappreciated role for lncRNA conserved fragments in the innate antiviral response, providing a strong foundation for developing nucleotide drugs based on conserved functional fragments within lncRNAs.Rationale Recurrent and metastatic cancers often undergo a period of dormancy, which is closely associated with cellular quiescence, a state whereby cells exit the cell cycle and are reversibly arrested in G0 phase. Curative cancer treatment thus requires therapies that either sustain the dormant state of quiescent cancer cells, or preferentially, eliminate them. However, the mechanisms responsible for the survival of quiescent cancer cells remain obscure. Methods Dual genome-editing was carried out using a CRISPR/Cas9-based system to label endogenous p27 and Ki67 with the green and red fluorescent proteins EGFP and mCherry, respectively, in melanoma cells. Analysis of transcriptomes of isolated EGFP-p27highmCherry-Ki67low quiescent cells was conducted at bulk and single cell levels using RNA-sequencing. The extracellular acidification rate and oxygen consumption rate were measured to define metabolic phenotypes. SiRNA and inducible shRNA knockdown, chromatin immunoprecipitation and luciferase reporter assaysuiescence, uncover the high selectivity of c-Myc in activating OXPHOS genes in quiescent cells, and propose OXPHOS targeting as a potential therapeutic avenue to counter cancer cells in quiescence.Rationale The progressive disruption of extracellular matrix (ECM) proteins, particularly early elastin fragmentation followed by abnormalities in collagen fibril organization, are key pathological processes that contribute to dissecting abdominal aortic aneurysm (AAA) pathogenesis. Lysyl hydroxylase 1 (LH1) is essential for type I/III collagen intermolecular crosslinking and stabilization. However, its function in dissecting AAA has not been explored. Here, we investigated whether LH1 is significantly implicated in dissecting AAA progression and therapeutic intervention. Methods and Results Sixteen-week-old male LH1-deficient and wild-type (WT) mice on the C57Bl/6NCrl background were infused with angiotensin II (Ang II, 1000 ng/kg per minute) via subcutaneously implanted osmotic pumps for 4 weeks. Ang II increased LH1 levels in the abdominal aortas of WT mice, whereas mice lacking LH1 developed dissecting AAA. To evaluate the related mechanism, we performed whole-transcriptomic analysis, which demonstrated that LH1 deficiency aggravated gene transcription alterations; in particular, the expression of thrombospondin-1 was markedly upregulated in the aortas of LH1-deficient mice.
Here's my website: