A bioengineering method for modeling alveolar Rhabdomyosarcoma and assessing chemotherapy responses

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignant tumor. Treatment of RMS usually includes primary tumor resection along with systemic chemotherapy. Two-dimensional (2D) cell culture systems and animal models have been extensively used for investigating the potential efficacy of new RMS treatments. However, RMS cells behave differently in 2D culture than in vivo, which has recently inspired the adoption of three-dimensional (3D) culture environments. In the current paper, we will describe the detailed methodology we have developed for fabricating a 3D engineered model to study alveolar RMS (ARMS) in vitro. This model consists of a thermally cross-linked collagen disk laden with RMS cells that mimics the structural and bio-chemical aspects of the tumor extracellular matrix (ECM). This process is highly reproducible and produces a 3D engineered model that can be used to analyze the cytotoxicity and autophagy induction of drugs on ARMS cells. The most improtant bullet points are as following: • We fabricated 3D model of ARMS. • The current ARMS 3D model can be used for screening of chemotherapy drugs. • We developed methods to detect apoptosis and autophagy in ARMS 3D model to detect the mechansims of chemotherapy agents

Autophagy, Unfolded Protein Response, and Neuropilin-1 Cross-Talk in SARS-CoV-2 Infection: What Can Be Learned from Other Coronaviruses

The COVID-19 pandemic is caused by the 2019–nCoV/SARS-CoV-2 virus. This severe acute respiratory syndrome is currently a global health emergency and needs much effort to generate an urgent practical treatment to reduce COVID-19 complications and mortality in humans. Viral infection activates various cellular responses in infected cells, including cellular stress responses such as unfolded protein response (UPR) and autophagy, following the inhibition of mTOR. Both UPR and autophagy mechanisms are involved in cellular and tissue homeostasis, apoptosis, innate immunity modulation, and clearance of pathogens such as viral particles. However, during an evolutionary arms race, viruses gain the ability to subvert autophagy and UPR for their benefit. SARS-CoV-2 can enter host cells through binding to cell surface receptors, including angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1). ACE2 blockage increases autophagy through mTOR inhibition, leading to gastrointestinal complications during SARS-CoV-2 virus infection. NRP1 is also regulated by the mTOR pathway. An increased NRP1 can enhance the susceptibility of immune system dendritic cells (DCs) to SARS-CoV-2 and induce cytokine storm, which is related to high COVID-19 mortality. Therefore, signaling pathways such as mTOR, UPR, and autophagy may be potential therapeutic targets for COVID-19. Hence, extensive investigations are required to confirm these potentials. Since there is currently no specific treatment for COVID-19 infection, we sought to review and discuss the important roles of autophagy, UPR, and mTOR mechanisms in the regulation of cellular responses to coronavirus infection to help identify new antiviral modalities against SARS-CoV-2 virus

Does Using Highly Porous Tantalum in Revision Total Hip Arthroplasty Reduce the Rate of Periprosthetic Joint Infection? A Systematic Review and Meta-Analysis

Background: Studies suggest tantalum (Ta) implants may have inherent antibacterial properties. However, there is no consensus regarding the effectiveness of Ta in preventing periprosthetic joint infection (PJI) after revision total hip arthroplasty (rTHA). Methods: We searched 5 main databases for articles reporting the rate of PJI following rTHA using Ta implants from inception to February 2022. The PJI rates of the Ta group were meta-analyzed, compared with the control group, and represented as relative risks (RRs) in forest plots. Results: We identified 67 eligible studies (28,414 joints) for assessing the prevalence of PJI following rTHA using Ta implants. Among these studies, only 9 compared the Ta implant group with a control group. The overall PJI rate following rTHA using Ta implants was 2.9% (95% confidence interval [CI]: 2.2%-3.8%), while it was 5.7% (95% CI = 4.1%-7.8%) if only septic revisions were considered. Comparing the Ta and control groups showed a significantly lower PJI rate following all-cause rTHA with an RR = 0.80 (95% CI = 0.65-0.98, P < .05). There was a trend toward lower reinfection rates in the Ta group after rTHA in septic cases, although the difference was not statistically significant (RR = 0.75, 95% CI = 0.44-1.29, P = .30). Conclusions: Ta implants are associated with a lower PJI rate following all-cause rTHA but not after septic causes. Despite positive results, the clinical significance of Ta still remains unclear since the PJI rate was only reduced by 20%. Level of Evidence: IV

The effects of low-fat dairy products fortified with 1500 IU vitamin D3 on serum liver function biomarkers in adults with abdominal obesity: a randomized controlled trial

Abstract Introduction Vitamin D deficiency has been reported to affect liver function biomarkers. This study was aimed to investigate the effect of consuming vitamin D fortified low-fat dairy products on liver function tests in adults with abdominal obesity. Methods This total blinded randomized controlled trial was undertaken on otherwise healthy abdominally obese adults living in Mashhad, Iran. Milk and yogurt were fortified with 1500 IU vitamin D3 nano-capsules. Participants were randomized to receive fortified milk (n = 73), plain milk (n = 73), fortified yogurt (n = 69), and plain yogurt (n = 74) for 10 weeks. Blood samples were taken at baseline and at the end of the study to assess serum levels of vitamin D, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), and Gamma glutamyl transferase. Results A total of 289 participants completed the study (54% female). The groups were homogenous in terms of age, sex, weight, energy intake, and physical activity level (p-value > 0.05). After the trial, vitamin D serum levels were significantly increased in both groups receiving fortified products (both p < 0.001). There was a significant time*group effect only in serum ALP (p < 0.001). Conclusion Consumption of dairy products fortified by 1500 IU vitamin D3 might have detrimental effects on serum levels of some liver enzymes in individuals with abdominal obesity. Further studies needed to determine these effects and underlying mechanisms. Trial registration: IRCT20101130005280N27