The fused-deposition modeling (FDM) process is carried out at an elevated temperature, preventing the addition of biological factors, drugs, bioactive compounds, etc, during fabrication. To overcome this disadvantage, a 3D interlinked porous polylactic acid (PLA) scaffold was fabricated by FDM, followed by the embedding of a polycaprolactone (PCL) scaffold into the pores of the PLA at room temperature, yielding a PLA-PCL scaffold. In addition, PLA-PCL scaffolds with nanohydroxyapatite (PLA-PCL-nHAP) and multiwalled carbon nanotubes (PLA-PCL-MWCNT) were also fabricated. Here, the FDM-fabricated PLA scaffold functions as the structural component, whereas the embedded PCL scaffold acts as the functional component, which provides a the ability to functionalize the scaffolds with the desired chemical or biological materials. The embedding process is straightforward, cost effective, and does not require sophistication. A mechanical characterization of the scaffolds suggests that the Young’s modulus of the PLA-PCL scaffold (16.02 MPa) was higher than that of the FDM-fabricated PLA (9.98 MPa) scaffold, by virtue of embedded PCL matrix. In addition, finite element analysis showed that the von Mises stress on a mandible with scaffolds was 4.04 MPa, whereas for a mandible with a defect, it was 6.7 MPa, confirming the stress distribution efficiency and mechanical stability of these scaffolds. Furthermore, field emission-scanning electron microscope analysis implied the presence of interlinked porous structures with pore diameters of 50 µm to 300 µm. X-ray diffraction results revealed an increased crystallinity (%) in the embedded models (PLA-PCL, PLA-PCL-nHAP and PLA-PCL-MWCNT), compared to a PLA printed scaffold. Additionally, Raman analysis revealed that the embedding process did not cause chemical alterations in the polymeric chains. In vitro analysis with human osteoblasts demonstrated the osteoconductive nature of the scaffold, which supported mineralization. In brief, the advantage of our model is that it helps to overcome the difficulties of manufacturing a filament with the desired additives for FDM, and offers the ability to incorporate the desired concentrations of heat-labile bioactive molecules during the embedding process at ambient temperatures.
We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment.Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.
Introduction and Aim: Enhanced External Counterpulsation (EECP) is an outpatient treatment to improve myocardial perfusion in chronic stable angina patients. We studied the clinical response of heart failure patients' improvement in the functional class and exercise tolerance with EECP. Materials and Methods: We prospectively evaluated twenty-six patients, who had completed a course of EECP with pre and post six minutes’ walk test, functional ability assessed by the New York heart association (NYHA) classification, renal parameters, lipid profile, and diastole to systole(d/s) ratio in terms of Peak amplitude (P) and Area (A) under the curve value. Results: The study group's mean age is of 56 years. The mean left ventricular ejection fraction (LVEF) is 31.44± 5.5%. Patients' demography includes 81% were male, 30% with hypertension (HT),50% with diabetes mellitus (DM), 30%chronic smokers, 61% of them had triple vessel disease (TVD). All the patients improved by a minimum of one NYHA class improvement, Serum urea reduced from 34.37 ± 20.28 to 27.24 ± 18.73 mg/dL (P = 0.002), C-Reactive protein (CRP) reduced from 4.6± 8.0 to 3.76 ± 5.1 mg/dL (P = 0.62). In the measured lipid panel test, only low-density lipoprotein (LDL) reduction from 94.41 ± 38.66 to 80.51 ± 35.09 mg/dL was statistically significant (P =0.03). The six-minute walk test, post-EECP, improved significantly from 340.14 ± 68.5 to 385.5 ± 73.9 meters (P =0.0004). The LVEF increased from 31.44 ± 5.5 to 38.38 ± 8.69 % (P=0.001). Conclusion: EECP treatment significantly improves shortness of breath, six minutes walking distance, and ejection fraction in heart failure patients. The treatment significantly reduces serum urea and LDL level. These positive changes may be due to a sudden increase in cardiac output and hyperdynamic circulation during the treatment.
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