Indentation Probing of In Vitro Bovine Articular Cartilage: Effects on Chondrocyte Viability and Tissue Biomechanics

Osteoarthritis (OA) consists of a degenerative disease on articular cartilage, which is prone to excessive mechanical loading and frictional resistance that leads to the wear and tear of the tissue. These factors result in the progressive and incurable disease that affects millions of people worldwide. The goal is to characterize chondrocyte viability and the in vitro biomechanical properties of articular cartilage in two confined indentation studies. One study looks at the chondrocyte viability over seven days. The second compares the immediate effects of strain rates on chondrocyte viability and tissue biomechanics. Bovine cartilage explants are harvested, cultured, and then 40% strain indentation tests are conducted at the rates of 80% s-1 & 0.1% s-1 depending on the study. All samples are stained and imaged via confocal microscopy after indentation and twice more during the seven-day study. Tissue micro- and macro-mechanics was assessed by atomic force microscopy and by the indentation test instrument, respectively. At the rate of 80% s-1, chondrocyte viability did not significantly progress over seven days. A statistically significant decrease in chondrocyte viability between 80% s-1 & 0.1% s-1 was noted along with a statistically significant decrease in the stiffness of the indented area. Cartilage damage propagation over seven days did not occur and cartilage mechanics is dependent on strain rate. For developing a more accurate post-injury OA development model, further biomechanical information needs to be elucidated

Loss of Scribble confers cisplatin resistance during NSCLC chemotherapy via Nox2/ROS and Nrf2/PD-L1 signaling

Background: Cisplatin resistance remains a major clinical obstacle to the successful treatment of non-small cell lung cancer (NSCLC). Scribble contributes to ROS-induced inflammation and cisplatin-elevated toxic reactive oxygen species (ROS) promotes cell death. However, it is unknown whether and how Scribble is involved in the cisplatin-related cell death and the underlying mechanism of Scribble in response to chemotherapies and in the process of oxidative stress in NSCLC. Methods: We used two independent cohorts of NSCLC samples derived from patients treated with platinumcontaining chemotherapy and xenograft modeling in vivo. We analyzed the correlation between Scribble and Nox2 or Nrf2/PD-L1 both in vivo and in vitro, and explored the role of Scribble in cisplatin-induced ROS and apoptosis. Findings: Clinical analysis revealed that Scribble expression positively correlatedwith clinical outcomes and chemotherapeutic sensitivity in NSCLC patients. Scribble protected Nox2 protein from proteasomal degradation. Scribble knockdown induced cisplatin resistance by blocking Nox2/ROS and apoptosis in LRR domaindependent manner. In addition, low levels of Scribble correlated with high levels of PD-L1 via activation of Nrf2 transcription in vivo and in vitro. Interpretations: Our study revealed that polarity protein Scribble increased cisplatin-induced ROS generation and is beneficial to chemotherapeutic outcomes in NSCLC. Although Scribble deficiency tends to lead to cisplatin resistance by Nox2/ROS and Nrf2

A rare case of recurrent primary dumbbell-shaped spinal hydatidosis

Spinal hydatidosis, which affects the thoracic vertebrae, is not only an extremely rare occurrence, but is also characterized by a high recurrence rate. Here, we reported a case of 67-years-old man who presented with recurrent spinal hydatid disease. The condition was originally misdiagnosed as Schwannoma via medical imaging, but eventually confirmed by postoperative pathology. He was subjected to surgery, combined with adjuvant drug therapy. Unfortunately, he experienced recurrent spinal hydatid disease and had to undergo hydatid cyst excision in over 5 years

Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors

Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development