COVID-19 is not spreading over a level playing field; structural racism is embedded within the fabric of American culture, infrastructure investments, and public policy and fundamentally drives ...inequities. The same racism that has driven the systematic dismantling of the American social safety net has also created the policy recipe for American structural vulnerability to the impacts of this and other pandemics. The Bronx provides an important case study for investigating the historical roots of structural inequities showcased by this pandemic; current lived experiences of Bronx residents are rooted in the racialized dismantling of New York City's public infrastructure and systematic disinvestment. The story of the Bronx is repeating itself, only this time with a novel virus. To address the root causes of inequities in cases and deaths due to COVID-19, we need to focus not just on restarting the economy but also on reimagining the economy, divesting of systems rooted in racism, and the devaluation of Black and Brown lives.
Photothermal therapy (PTT) is a promising cancer treatment modality, but PTT generally requires direct access to the source of light irradiation, thus precluding its utility against disseminated, ...metastatic tumors. Here, we demonstrate that PTT combined with chemotherapy can trigger potent anti-tumor immunity against disseminated tumors. Specifically, we have developed polydopamine-coated spiky gold nanoparticles as a new photothermal agent with extensive photothermal stability and efficiency. Strikingly, a single round of PTT combined with a sub-therapeutic dose of doxorubicin can elicit robust anti-tumor immune responses and eliminate local as well as untreated, distant tumors in >85% of animals bearing CT26 colon carcinoma. We also demonstrate their therapeutic efficacy against TC-1 submucosa-lung metastasis, a highly aggressive model for advanced head and neck squamous cell carcinoma (HNSCC). Our study sheds new light on a previously unrecognized, immunological facet of chemo-photothermal therapy and may lead to new therapeutic strategies against advanced cancer.
Summary
Background
Nasal polyposis is a multi‐factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) ...accumulation are involved in the pathogenesis of nasal polyposis.
Objective
The aim of this study was to study the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on transforming growth factor (TGF)‐β1‐induced myofibroblast differentiation and ECM accumulation in nasal polyp‐derived fibroblasts (NPDFs).
Methods
Nasal polyp‐derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA was treated in TGF‐β1‐induced NPDFs. Expression levels of HDAC2, α‐smooth muscle actin (SMA), TGF‐β1, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2/3 and Smad7 were determined by RT‐PCR, western blot and/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC2 inhibition by TSA or HDAC2 silencing was established by RT‐PCR and western blot. The epigenetic effect on α‐SMA gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67‐positive cell staining and cytotoxicity was assessed by 3‐(4,5‐ dimethylthiazol‐2yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay.
Results
The expression levels of HDAC2, α‐SMA and TGF‐β1 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA and HDAC2 silencing inhibited expression levels α‐SMA, collagen and HDAC2. TSA induced hyperacetylation of histone and suppressed opening of α‐SMA gene promoter in TGF‐β1‐induced NPDFs. TSA inhibited TGF‐β1‐induced Smad 2/3 and rescued TGF‐β1‐suppressed Smad7 signalling pathway. Finally, TSA blocked proliferation in TGF‐β1‐induced NPDFs and has no cytotoxic effect in NPDFs.
Conclusions and Clinical Relevance
These results suggest that HDAC inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.
Summary
Smoking is a major environmental factor associated with periodontal diseases. However, we still have a very limited understanding of the relationship between smoking and subgingival ...microflora in the global population. Here, we investigated the composition of subgingival bacterial communities from the pooled plaque samples of smokers and non‐smokers, 134 samples in each group, in Korean patients with moderate chronic periodontitis using 16S rRNA gene‐based pyrosequencing. A total of 17,927 reads were analyzed and classified into 12 phyla, 126 genera, and 394 species. Differences in bacterial communities between smokers and non‐smokers were examined at all phylogenetic levels. The genera Fusobacterium, Fretibacterium, Streptococcus, Veillonella, Corynebacterium, TM7, and Filifactor were abundant in smokers. On the other hand, Prevotella, Campylobacter, Aggregatibacter, Veillonellaceae GQ422718, Haemophilus, and Prevotellaceae were less abundant in smokers. Among species‐level taxa occupying > 1% of whole subgingival microbiome of smokers, higher abundance (≥ 2.0‐fold compared to non‐smokers) of seven species or operational taxonomic units (OTUs) was found: Fusobacterium nucleatum, Neisseria sicca, Neisseria oralis, Corynebacterium matruchotii, Veillonella dispar, Filifactor alocis, and Fretibacterium AY349371. On the other hand, lower abundance of 11 species or OTUs was found in smokers: Neisseria elongata, six Prevotella species or OTUs, Fusobacterium canifelinum, Aggregatibacter AM420165, Selenomonas OTU, and Veillonellaceae GU470897. Species richness and evenness were similar between the groups whereas diversity was greater in smokers than non‐smokers. Collectively, the results of the present study indicate that differences exist in the subgingival bacterial community between smoker and non‐smoker patients with chronic moderate periodontitis in Korea, suggesting that cigarette smoking considerably affects subgingival bacterial ecology.
Topological insulators have been proposed to be best characterized as bulk magnetoelectric materials that show response functions quantized in terms of fundamental physical constants. Here, we lower ...the chemical potential of three-dimensional (3D) Bi₂Se₃ films to ~3O meV above the Dirac point and probe their low-energy electrodynamic response in the presence of magnetic fields with high-precision time-domain terahertz polarimetry. For fields higher than 5 tesla, we observed quantized Faraday and Kerr rotations, whereas the dc transport is still semiclassical. A nontrivial Berry's phase offset to these values gives evidence for axion electrodynamics and the topological magnetoelectric effect. The time structure used in these measurements allows a direct measure of the fine-structure constant based on a topological invariant of a solid-state system.
While conventional approaches for inflammatory bowel diseases mainly focus on suppressing hyperactive immune responses, it remains unclear how to address disrupted intestinal barriers, dysbiosis of ...the gut commensal microbiota and dysregulated mucosal immune responses in inflammatory bowel diseases. Moreover, immunosuppressive agents can cause off-target systemic side effects and complications. Here, we report the development of hyaluronic acid-bilirubin nanomedicine (HABN) that accumulates in inflamed colonic epithelium and restores the epithelium barriers in a murine model of acute colitis. Surprisingly, HABN also modulates the gut microbiota, increasing the overall richness and diversity and markedly augmenting the abundance of Akkermansia muciniphila and Clostridium XIVα, which are microorganisms with crucial roles in gut homeostasis. Importantly, HABN associated with pro-inflammatory macrophages, regulated innate immune responses and exerted potent therapeutic efficacy against colitis. Our work sheds light on the impact of nanotherapeutics on gut homeostasis, microbiome and innate immune responses for the treatment of inflammatory diseases.
The purpose of the current review was to evaluate how body composition can be utilised in athletes, paying particular attention to the bioelectrical impedance analysis (BIA) technique.
Various body ...composition methods are discussed, as well as the unique characteristics of athletes that can lead to large errors when predicting fat mass (FM) and fat-free mass (FFM). Basic principles of BIA are discussed, and past uses of the BIA technique in athletes are explored. Single-prediction validation studies and studies tracking changes in FM and FFM are discussed with applications for athletes.
Although extensive research in the area of BIA and athletes has been conducted, there remains a large gap in the literature pertaining to a single generalised athlete equation developed using a multiple-compartment model that includes total body water (TBW).
Until a generalised athlete-specific BIA equation developed from a multiple-compartment is published, it is recommended that generalised equations such as those published by Lukaski and Bolonchuk and Lohman be used in athletes. However, BIA equations developed for specific athletes may also produce acceptable values and are still acceptable for use until more research is conducted. The use of a valid BIA equation/device should produce values similar to those of hydrostatic weighing and dual-energy X-ray absorptiometry. However, researchers and practitioners need to understand the individual variability associated with BIA estimations for both single assessments and repeated measurements. Although the BIA method shows promise for estimating body composition in athletes, future research should focus on the development of general athlete-specific equations using a TBW-based three- or four-compartment model.
While nanoscale mimics of peroxidase have been extensively developed over the past decade or so, their catalytic efficiency as a key parameter has not been substantially improved in recent years. ...Herein, we report a class of highly efficient peroxidase mimic–nickel–platinum nanoparticles (Ni–Pt NPs) that consist of nickel-rich cores and platinum-rich shells. The Ni–Pt NPs exhibit a record high catalytic efficiency with a catalytic constant (K cat) as high as 4.5 × 107 s–1, which is ∼46- and 104-fold greater than the K cat values of conventional Pt nanoparticles and natural peroxidases, respectively. Density functional theory calculations reveal that the unique surface structure of Ni–Pt NPs weakens the adsorption of key intermediates during catalysis, which boosts the catalytic efficiency. The Ni–Pt NPs were applied to an immunoassay of a carcinoembryonic antigen that achieved an ultralow detection limit of 1.1 pg/mL, hundreds of times lower than that of the conventional enzyme-based assay.
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