Should we treat soft tissue injuries with Actovegin?

Actovegin is a biological drug produced from deproteinised hemodialysate of calf serum with over 50 years of history for its clinical use. There have been many in vitro studies to speculate its potential role and mechanism of action in cells; due to the nature of this drug and serum based culture techniques for most in vitro experiments, presumptuous conclusions and claims from these studies on performance enhancement should be cautiously interpreted. There have been well-designed human in vivo studies suggesting it does not enhance human performance, and has potentially good clinical applications to treat injuries, strokes and diabetes. Recently, evidence has emerged suggesting Actovegin has anti-inflammatory and anti-apoptotic effects on injured tissues; further clinical research is needed to define these effects. This article also provides a narrative review of Actovegin summarizing outcomes from recent publications

Actovegin equal to performance enhancing drug doping: fact or fiction?

Actovegin is a biological drug that has been used for the treatment of sports muscle injuries. Several in vitro studies have shed light on potential mechanisms of action and the drug has consistently demonstrated its potential to reduce return from injury time for muscle tears in elite athletes. Yet it was banned for a time under the International Olympic Committee (IOC) as a blood doping agent, this ban was based on presumptuous conclusions and subsequently lifted after no indisputable evidence could be provided. This editorial aims to provide readers with some of the key, objective facts relating to Actovegin and then based on this, will offer an informed opinion on its role in sports medicine. We also hope to highlight the importance of evidence-based medicine, particularly in the volatile field of Sports Medicine, and the need for facts, not fiction

Should we treat soft tissue injuries with Actovegin

Actovegin is a biological drug produced from deproteinised hemodialysate of calf serum with over 50 years of history for its clinical use. There have been many in vitro studies to speculate its potential role and mechanism of action in cells; due to the nature of this drug and serum based culture techniques for most in vitro experiments, presumptuous conclusions and claims from these studies on performance enhancement should be cautiously interpreted. There have been well-designed human in vivo studies suggesting it does not enhance human performance, and has potentially good clinical applications to treat injuries, strokes and diabetes. Recently, evidence has emerged suggesting Actovegin has anti-inflammatory and anti apoptotic effects on injured tissues; further clinical research is needed to define these effects. This article also provides a narrative review of Actovegin summarizing outcomes from recent publications

Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17

Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in modulating plaque stability. More recently, the ADAMTS proteases, which are known to play a key role in the control of cartilage degradation during arthritis, have been found to be expressed in atherosclerotic lesions and suggested to have potentially important functions in the control of plaque stability. Unfortunately, the action of cytokines on the expression of ADAMTS family in macrophages is poorly understood. We have investigated the effect of classical cytokines (IFN-γ and TGF-β) and those that have been recently identified (TL1A and IL-17) on the expression of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS members was induced during differentiation of monocytes into macrophages. TGF-β had a differential action with induction of ADAMTS-1 and -5 expression and attenuation in the levels of ADAMTS-4. In contrast, IFN-γ suppressed the expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL-1A or IL-17A alone had little effect on the expression of all the members, they induced their expression synergistically when present together. These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis

Effect of Indocyanine Green and Illumination on Gene Expression in Human Retinal Pigment Epithelial Cells

PURPOSE. To investigate the biological effects of indocyanine green (ICG) and acute illumination on human retinal pigment epithelial (RPE) cells. METHODS. Three concentrations (0, 0.25, and 2.5 mg/mL) of ICG were applied to ARPE19 cells for 1 minute. After isotonic rinsing, the cells were irradiated with a light beam with a wavelength spectrum from 400 to 800 nm and an output of 1850 lumens for 15 minutes. The cells were collected at timed intervals for the investigation of cell death and expression of stress-response genes by reverse transcription-polymerase chain reaction, immunofluorescence, and Western blot analysis. RESULTS. After ICG incubation, photoreactive changes were observed in the RPE cells. A reduction in cellular viability and considerable shrinkage of the cells were observed. The expressions of the apoptosis-related genes p53 and bax and the cell cycle arrest protein p21 were upregulated in cells treated with both ICG and light. Of the early-response genes, the expression of c-fos was specifically enhanced by light, with additive effects from the presence of ICG. Such stimulatory effects on these gene expressions were greater at 2.5 mg/mL than at 0.25 mg/mL ICG. CONCLUSIONS. ICG in the presence of acute illumination can elicit cell-cycle arrest and even apoptosis in RPE cells. The establishment of a safety level in the application of ICG in the region of 0.25 mg/mL is recommended. (Invest Ophthalmol Vis Sci

The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu