Correlation between chest CT severity score and laboratory indicators in patients with Coronavirus disease 2019 (COVID-19).

OBJECTIVE: The association between computed tomography (CT) and clinical severity of COVID-19 has been demonstrated. However, there are few studies on CT and laboratory indicators in patients in COVID-19. Our aim was to explore the correlation between chest CT images and laboratory indicators of patients with COVID-19 pneumonia. METHODS: This was a retrospective study of patients with COVID-19 diagnosed and treated at the Affiliated Hospital of Putian University from 24 January 2020 to 6 March 2020. The correlation test between first chest CT score and blood cell analysis, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), blood biochemistry and T lymphocyte subsets (T-Ls) was investigated. RESULTS: Among the 56 patients, there were 36 (64.3%) males and 20 (35.7%) females. The mean age of the patients was 46.54 ± 15.82 (range, 15-86) years. The CT score in the moderate group was higher than in the mild group (5.06 ± 0.77 vs 1.87 ± 0.88, P < .05), and higher in the severe group than in the moderate and mild groups (10.71 ± 4.21, P < .05). In addition, the ESR was significantly higher in the severe group than mild group (32.00 (26.04, 58.24) vs 11.00 (7.84, 24.70) mm/h, P < .05). The CD3, CD4, CD8 and CD4/CD8 cells were not different (all P > .05). The CT scores of all patients correlated positively with CRP, LDH and ESR (all P < .01). CONCLUSION: The chest CT characteristics of patients with COVID-19 correlated positively with CRP, ESR and LDH, which may use one of the indicators for the assessment of disease severity.

The role of Twist1 in mutant huntingtin-induced transcriptional alterations and neurotoxicity.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the huntingtin protein (Htt). Transcriptional dysregulation is an early event in the course of HD progression and is thought to contribute to disease pathogenesis, but how mutant Htt causes transcriptional alterations and subsequent cell death in neurons is not well understood. RNA-Seq analysis revealed that expression of a mutant Htt fragment in primary cortical neurons leads to robust gene expression changes before neuronal death. Basic helix-loop-helix transcription factor Twist1, which is essential for embryogenesis and is normally expressed at low levels in mature neurons, was substantially up-regulated in mutant Htt-expressing neurons in culture and in the brains of HD mouse models. Knockdown of Twist1 by RNAi in mutant Htt-expressing primary cortical neurons reversed the altered expression of a subset of genes involved in neuronal function and, importantly, abrogated neurotoxicity. Using brain-derived neurotrophic factor (Bdnf), which is known to be involved in HD pathogenesis, as a model gene, we found that Twist1 knockdown could reverse mutant Htt-induced DNA hypermethylation at the Bdnf regulatory region and reactivate Bdnf expression. Together, these results suggest that Twist1 is an important upstream mediator of mutant Htt-induced neuronal death and may in part operate through epigenetic mechanisms.

A topical aqueous oxygen emulsion stimulates granulation tissue formation in a porcine second-degree burn wound.

BACKGROUND: Oxygen is an essential substance for wound healing. Limited studies have shown that topical oxygen can influence healing. This study evaluated the effects of a Topical Oxygen Emulsion (TOE) on burn wound healing. METHODS: A porcine second-degree burn wound model was used in the study. Burn wounds were randomly assigned to TOE, vehicle control, and no-treatment (air) groups. Effects of TOE on the granulation tissue formation and angiogenesis were studied using hematoxylin and eosin histological analysis. Protein production and gene expression of types I and III collagen and vascular endothelial growth factor (VEGF) were determined using immunofluorescent staining and Reverse Transcription and Polymerase Chain Reaction (RT-PCR), respectively. RESULTS: The TOE treated wounds exhibited better angiogenesis and granulation tissue formation by histology examination. The immunofluorescence staining and RT-PCR analysis demonstrated that protein production and mRNA expression of VEGF and collagen III were significantly higher in TOE treatment group than vehicle alone and air control groups, while there was no significant difference in the level of collagen I. CONCLUSIONS: Our data demonstrate that TOE enhances burn wound healing via stimulating the expression of VEGF and type III collagen and strongly indicates the potential use of TOE in wounds.

Effects of a topical aqueous oxygen emulsion on collagen deposition and angiogenesis in a porcine deep partial-thickness wound model.

A porcine deep partial-thickness wound model was used to evaluate the effects of a newly developed topical aqueous oxygen emulsion (TOE) on wound repair. The wounds were treated with TOE, which contains super-saturated oxygen or vehicle control. Semiquantitative immunofluorescent staining was performed to examine protein production for type I and type III collagen and vascular endothelial growth factor (VEGF). Immunofluorescent staining revealed higher protein levels of type I and type III collagen and VEGF in the TOE treatment group. Histological analysis also revealed improved angiogenesis and granulation tissue formation with topical TOE treatment and was consistent with the protein expression. In addition, the histology examination demonstrated faster epithelialization in wounds treated with TOE. The study suggests that sustained high levels of oxygen released by TOE may promote the process of wound repair through increasing collagen deposition and angiogenesis as well as stimulating epithelialization.

Phosphate ester derivatives of homocamptothecin: synthesis, solution stabilities and antitumor activities.

Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0.

A low interleukin-2 receptor signaling threshold supports the development and homeostasis of T regulatory cells.

Interleukin-2 receptor (IL-2R) signaling is essential for T regulatory (Treg) cell development and homeostasis. Here, we show that expression of IL-2Rbeta chains that lack tyrosine residues important for the association of the adaptor Shc and the transcription factor STAT5 in IL-2Rbeta-deficient mice resulted in production of a normal proportion of natural Treg cells that suppressed severe autoimmunity related with deficiency in IL-2 or IL-2R. These mutant IL-2Rbeta chains supported suboptimal and transient STAT5 activation that upregulate the transcription factor Foxp3 to normal amounts in natural, but not induced, Treg cells. Nevertheless, gene expression profiling revealed many targets in peripheral natural Treg cells that were IL-2 dependent and a substantial overlap between the Treg cell IL-2-dependent gene program and the Treg cell transcriptional signature. Collectively, these findings demonstrate that a critical, and perhaps minor, subset of IL-2-dependent targets is indexed to a low IL-2R signaling threshold and that a substantial proportion of the Treg cell gene program is regulated by IL-2.

IL-2 family of cytokines in T regulatory cell development and homeostasis.

INTRODUCTION: Interleukin 2 (IL-2) induces an essential signal for T regulatory (Treg) cells. Without a functional IL-2R, only immature CD4(+) Foxp3(low) CD25(neg) T cells develop, and these cells fail to suppress autoreactive T cells in the periphery. DISCUSSION: IL-2 functions during Treg cell development by upregulating Foxp3 and CD25 and by increasing the number of thymic Treg cells. Upon exiting the thymus during neonatal life, IL-2 is responsible for rapid amplification of the number of Treg cells in peripheral lymph nodes to insure suppression of autoreactive T cells that escape negative selection, thereby maintaining tolerance. The homeostasis of Treg cells in mature immunocompetent mice also depends on IL-2. However, there is an alternative mechanism for Treg cells homeostasis that may represent a minor IL-2-independent pathway or the consequence of weak and very transient IL-2R signaling. CONCLUSION: Thus, IL-2 provides importance signals for Treg cell development and for their homeostasis in peripheral immune tissues.

Effect of the 1,450 nm diode non-ablative laser on collagen expression in an artificial skin model.

BACKGROUND AND OBJECTIVE: The 1,450-nm Smoothbeam Laser is a diode laser equipped with a cryogen cooling spray. Primary objectives were to evaluate the effects of this non-ablative laser on Apligraf (bioengineered skin-substitute) and to document its use as a model for non-ablative procedures. We also measured the effects of laser fluence levels on collagen and elastin expression. STUDY DESIGN/MATERIALS AND METHODS: Three sheets of Apligraf were used for this study. Each received six separate laser applications at 4J, 6J, 8J, 10 J, 12J, and 14J. The sheets were then incubated with 10% CO(2) at 37 degrees C and samples were collected and analyzed 3 days later, using RT-PCR and immunofluorescent staining. RESULTS: Collagen III expressions significantly increased in both mRNA and protein levels at approximately 12 J. CONCLUSIONS: There appears to be a threshold effect where there is very little increased collagen III mRNA and protein expression until the laser fluence reaches around 12J.