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15,149 result(s) for "Ling, Hui"
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Cellular senescence in cancer: from mechanisms to detection
Cellular senescence is considered a crucial process for tumour suppression, which can be facilitated by immune surveillance. However, when senescent cells persist in tissues, they can also trigger a plethora of tumour‐promoting effects. Here, we discuss the main hallmarks, mechanisms and roles of senescence in cancer and provide a comprehensive revision of the available tools for its detection. Senescence refers to a cellular state featuring a stable cell‐cycle arrest triggered in response to stress. This response also involves other distinct morphological and intracellular changes including alterations in gene expression and epigenetic modifications, elevated macromolecular damage, metabolism deregulation and a complex pro‐inflammatory secretory phenotype. The initial demonstration of oncogene‐induced senescence in vitro established senescence as an important tumour‐suppressive mechanism, in addition to apoptosis. Senescence not only halts the proliferation of premalignant cells but also facilitates the clearance of affected cells through immunosurveillance. Failure to clear senescent cells owing to deficient immunosurveillance may, however, lead to a state of chronic inflammation that nurtures a pro‐tumorigenic microenvironment favouring cancer initiation, migration and metastasis. In addition, senescence is a response to post‐therapy genotoxic stress. Therefore, tracking the emergence of senescent cells becomes pivotal to detect potential pro‐tumorigenic events. Current protocols for the in vivo detection of senescence require the analysis of fixed or deep‐frozen tissues, despite a significant clinical need for real‐time bioimaging methods. Accuracy and efficiency of senescence detection are further hampered by a lack of universal and more specific senescence biomarkers. Recently, in an attempt to overcome these hurdles, an assortment of detection tools has been developed. These strategies all have significant potential for clinical utilisation and include flow cytometry combined with histo‐ or cytochemical approaches, nanoparticle‐based targeted delivery of imaging contrast agents, OFF‐ON fluorescent senoprobes, positron emission tomography senoprobes and analysis of circulating SASP factors, extracellular vesicles and cell‐free nucleic acids isolated from plasma. Here, we highlight the occurrence of senescence in neoplasia and advanced tumours, assess the impact of senescence on tumorigenesis and discuss how the ongoing development of senescence detection tools might improve early detection of multiple cancers and response to therapy in the near future.
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients
The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19. Higher viral loads soon after symptom onset indicate the need for isolation strategies different from those used for the earlier SARS epidemic.
Impacts of global change on the phyllosphere microbiome
Plants form complex interaction networks with diverse microbiomes in the environment, and the intricate interplay between plants and their associated microbiomes can greatly influence ecosystem processes and functions. The phyllosphere, the aerial part of the plant, provides a unique habitat for diverse microbes, and in return the phyllosphere microbiome greatly affects plant performance. As an open system, the phyllosphere is subjected to environmental perturbations, including global change, which will impact the crosstalk between plants and their microbiomes. In this review, we aim to provide a synthesis of current knowledge of the complex interactions between plants and the phyllosphere microbiome under global changes and to identify future priority areas of research on this topic.
Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study
Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed. Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission. Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak. US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK.
Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases
Background Jaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis. Main body The major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 ( ATP8B1 ), BSEP ( ABCB11 ), or MDR3 ( ABCB4 ). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway. Short conclusion Understanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.
Accessing chiral sulfones bearing quaternary carbon stereocenters via photoinduced radical sulfur dioxide insertion and Truce–Smiles rearrangement
From the viewpoint of synthetic accessibility and functional group compatibility, photoredox-catalyzed sulfur dioxide insertion strategy enables in situ generation of functionalized sulfonyl radicals from easily accessible starting materials under mild conditions, thereby conferring broader application potential. Here we present two complementary photoinduced sulfur dioxide insertion systems to trigger radical asymmetric Truce–Smiles rearrangements for preparing a variety of chiral sulfones that bear a quaternary carbon stereocenter. This protocol features broad substrate scope and excellent stereospecificity. Aside from scalability, the introduction of a quaternary carbon stereocenter at position β to bioactive molecule-derived sulfones further demonstrates the practicality and potential of this methodology. The preparation of chiral sulfones featuring quaternary carbon stereocenters remains challenging. Here the authors report the synthesis of such compounds via a multicomponent reaction involving a photoinduced radical sulfur dioxide insertion followed by an asymmetric Truce–Smiles rearrangement.
MIR4435-2HG Is a Potential Pan-Cancer Biomarker for Diagnosis and Prognosis
The lncRNA MIR4435-2 host gene (MIR4435-2HG) is located on human chromosome 2q13, and its expression is up-regulated in 18 tumors. MIR4435-2HG participates in 6 signaling pathways to promote tumorigenesis, including the TGF-β signaling pathway, Wnt/β-catenin signaling pathway, MDM2/p53 signaling pathway, PI3K/AKT signaling pathway, Hippo signaling pathway, and MAPK/ERK signaling pathway. MIR4435-2HG competitively binds with 20 miRNAs to form a complex ceRNA network, thereby regulating the expression of downstream target genes. The high expression of MIR4435-2HG is also closely related to the clinicopathological characteristics and poor prognosis of a variety of tumors. Also, the high expression of MIR4435-2HG in peripheral blood or serum has the value of predicting the risk of 9 tumors. In addition, MIR4435-2HG participates in the mechanism of action of three cancer drugs, including resveratrol for the treatment of lung cancer, cisplatin for non-small cell lung cancer and colon cancer, and carboplatin for triple-negative breast cancer. This article systematically summarizes the diagnostic and prognostic value of MIR4435-2HG in a variety of tumors and outlines the ceRNA network and signaling pathways related to MIR4435-2HG, which will provide potential directions for future MIR4435-2HG research.
The effect of cognitive-based training for the healthy older people: A meta-analysis of randomized controlled trials
From the perspective of disease prevention, the enhancement of cognitive function among the healthy older people has become an important issue in many countries lately. This study aim to investigate the effect of cognitive-based training on the overall cognitive function, memory, attention, executive function, and visual-spatial ability of the healthy older people. Cochrane, PubMed, EMBASE, MEDLINE, PsycINFO, and CINAHL of selected randomized controlled trials (RCTs), and previous systematic reviews were searched for eligible studies. The population focused on this study were healthy older people who participated in randomized controlled trials that investigated the effectiveness of cognitive-based training. The outcomes including change in overall cognitive function, memory, attention, executive function, and visual-spatial ability. We collected a total of 31 RCTs, the results showed that cognitive-based training has a moderate effect on overall cognitive function (g = 0.419; 95%CI = 0.205-0.634) and executive function (g = 0.420; 95%CI = 0.239-0.602), and a small effect on the memory (g = 0.354; 95%CI = 0.244-0.465), attention (g = 0.218; 95%CI = 0.125-0.311), and visual-spatial ability (g = 0.183;95%CI = 0.015-0.352) in healthy older people. Subgroup analysis indicated the intervention characteristics of ≧3 times each week (p = 0.042), ≧8 total training weeks (p = 0.003) and ≧24 total training sessions (p = 0.040) yields a greater effect size. Cognitive-based training is effective for the healthy older people. This improvement can represent a clinically important benefit, provide information about the use of cognitive-based training in healthy older people, and help the healthy older people obtain the greatest possible benefit in health promotion and disease prevention.
New opportunities for RGD-engineered metal nanoparticles in cancer
The advent of nanotechnology has opened new possibilities for bioimaging. Metal nanoparticles (such as gold, silver, iron, copper, etc.) hold tremendous potential and offer enormous opportunities for imaging and diagnostics due to their broad optical characteristics, ease of manufacturing technique, and simple surface modification. The arginine-glycine-aspartate (RGD) peptide is a three-amino acid sequence that seems to have a considerably greater ability to adhere to integrin adhesion molecules that exclusively express on tumour cells. RGD peptides act as the efficient tailoring ligand with a variety of benefits including non-toxicity, greater precision, rapid clearance, etc. This review focuses on the possibility of non-invasive cancer imaging using metal nanoparticles with RGD assistance. Graphical abstract