Biocompatible Human Placental Extracellular Matrix Derived Hydrogels.

Solubilizing extracellular matrix (ECM) materials and transforming them into hydrogels has expanded their potential applications both in vitro and in vivo. In this study, hydrogels are prepared by decellularization of human placental tissue using detergent and enzymes and by the subsequent creation of a homogenized acellular placental tissue powder (P-ECM). A perfusion-based decellularization approach is employed using detergent and enzymes. The P-ECM with and without gamma irradiation is then utilized to prepare P-ECM hydrogels. Physical and biological evaluations are conducted to assess the suitability of the P-ECM hydrogels for biocompatibility. The decellularized tissue has significantly reduced cellular content and retains the major ECM proteins. Increasing the concentration of P-ECM leads to improved mechanical properties of the P-ECM hydrogels. The biocompatibility of the P-ECM hydrogel is demonstrated through cell proliferation and viability assays. Notably, gamma-sterilized P-ECM does not support the formation of a stable hydrogel. Nonetheless, the use of HCl during the digestion process effectively decreases spore growth and bacterial bioburden. The study demonstrates that P-ECM hydrogels exhibit physical and biological attributes conducive to soft tissue reconstruction. These hydrogels establish a favorable microenvironment for cell growth and the need for investigating innovative sterilization methods.

Identification of critical autophagy-related proteins in diabetic retinopathy: A multi-dimensional computational study.

Diabetic retinopathy (DR) is a common consequence of diabetes mellitus and a primary cause of visual impairment in middle-aged and elderly individuals. DR is susceptible to cellular degradation facilitated by autophagy. In this study, we have employed a multi-layer relatedness (MLR) approach to uncover novel autophagy-related proteins involved in DR. The objective of MLR is to determine the relatedness of autophagic and DR proteins by incorporating both expression and prior-knowledge-based similarities. We constructed a prior knowledge-based network and identified the topologically significant novel disease-related candidate autophagic proteins (CAPs). Then, we evaluated their significance in a gene co-expression and a differentially-expressed gene (DEG) network. Finally, we investigated the proximity of CAPs to the known disease-related proteins. Leveraging this methodology, we identified three crucial autophagy-related proteins, TP53, HSAP90AA1, and PIK3R1, which can influence the DR interactome in various layers of heterogeneity of clinical manifestations. They are strongly related to multiple detrimental characteristics of DR, such as pericyte loss, angiogenesis, apoptosis, and endothelial cell migration, and hence may be used to prevent or delay the progression and development of DR. We evaluated one of the identified targets, TP53, in a cell-based model and found that its inhibition resulted in reduced angiogenesis in high glucose condition required to control DR.

Resolution of viral load in mild COVID-19 patients is associated with both innate and adaptive immune responses.

Over 90% of the COVID-19 patients manifest mild/moderate symptoms or are asymptomatic. Although comorbidities and dysregulation of immune response have been implicated in severe COVID-19, the host factors that associate with asymptomatic or mild infections have not been characterized. We have collected serial samples from 23 hospitalized COVID-19 patients with mild symptoms and measured the kinetics of SARS-CoV-2 viral load in respiratory samples and markers of inflammation in serum samples. We monitored seroconversion during the acute phase of illness and quantitated the amount of total IgG against the receptor-binding domain of SARS-CoV-2 and estimated the virus neutralization potential of these antibodies. Viral load decreased by day 8 in all the patients but the detection of viral RNA in saliva samples did not correlate well with viral RNA detection in nasopharyngeal/oropharyngeal swab samples. 25% of the virus-positive patients had no detectable neutralizing antibodies in the serum and in other cases, the efficiency of antibodies to neutralize SARS-CoV-2 B1.1.7 strain was lower as compared to the circulating virus isolate. Decrease in viral load coincided with increase in neutralizing antibodies and interferon levels in serum. Most patients showed no increase in inflammatory cytokines such as IL-1ß or IL-6, however, elevated levels of IL-7 and other inflammatory mediators such as TNF-α and IL-8 was observed. These data suggest that most mild infections are associated with absence of inflammation coupled with an active innate immune response, T-cell activation and neutralizing antibodies.