Filtering by
- Creators: School of Life Sciences
The prevalence of obesity continues to increase in the United States, along with its risk for other associated cardiovascular and metabolic diseases. Several therapeutic methods are aimed at targeting and reducing obesity, now defined as a state of chronic, low-grade inflammation (in addition to BMI > 30 kg/m2). In an attempt to expand on these therapeutic methods, research on the concept of browning in white adipose tissue (WAT) and brown adipose tissue (BAT) is being conducted. Brown adipose tissue (BAT), and a newly discovered type of adipocyte, beige adipocytes, are heavily involved in thermogenesis with the use of uncoupling protein-1 (UCP-1). This paper focuses on the analysis of common browning genes, ATP-related genes, and metabolic genes in varying biological groups in mice (Chow/High-Fat Diet and Inguinal FAT and Perigonadal Fat) and in humans (Lean/Obese and Subcutaneous WAT (SC) and Omental WAT (OM)) using methods such as RT-PCR and immunohistochemistry. The data obtained shows an increase in browning in the leaner group, specifically in the subcutaneous fat. Further, browning is significantly reduced in the obese groups of subjects and mice tested, in addition to omental/perigonadal versus subcutaneous/inguinal fat depots. Interestingly, two key ATP genes, UCP-1 and COX4I1 are vastly elevated in the OM WAT, indicating that browning may not be as important in the OM, but rather may have a potential role in SC. This is contrary to prior research findings that attempt to exclude mice surrogates in future experimentation of the browning phenomenon. Further experimentation is needed to expand on the findings of this paper.
Squeakie is a positive influence on the way the other characters perceive themselves. The shadow turns each character’s self-doubt and negative feelings into fuel, which he stores in a paintbrush. When he takes the fuel from the character, it fades their body color. Phan has anxiety and uses the 4-7-8 breathing technique to overcome her panic attacks. Her range of color is blue to light blue. Ovid feels guilty and exercises to take his mind off his guilty thoughts. Ovid is either red or light pink. Amelia is depressed and reframes her way of thinking to overcome her inability to fly. Visually she is green or light green. The shadow is later revealed as a misguided character who was just looking to escape the dream world and find friends.
The story is resolved by the stuffed animals joining forces with the perceived antagonist, the shadow, to operate a plane. They each use their strength of color to fuel the plane, which takes them back to the real world. When Sophia’s mom pulls the stuffed animals out of the washer, the shadow comes with them. The shadow, now a cat with rainbow patches, is instantly loved by Sophia. The story ends with the stuffed animals drying on the porch bench while Sophia plays with the shadow in the new backyard.
Minocycline is a tetracycline class broad spectrum antibiotic commonly used to treat severe acne and other skin infections. Propranolol is a beta blocker type heart medication primarily used to treat high blood pressure and irregular heartbeat. Chlorpromazine is a phenothiazine antipsychotic usually used for schizophrenia. Metformin is the most widely used first-line oral treatment for type-2 diabetes. Based on a literature survey, minocycline is expected to prevent the phosphorylation of STAT3, a transcription factor downstream of EGFR; propranolol is expected to disrupt EGFR trafficking; chlorpromazine is expected to target the PI3K/mTOR/Akt signaling pathway; metformin is believed to exploit vulnerabilities in cancer cell metabolism, as well as upregulate AMPK against the PI3K/mTOR/Akt pathway.
Efficacy of minocycline in inhibiting EGFR-driven STAT3 activation was investigated using western blot analysis. Our results demonstrate that Minocycline effectively inhibits activation of EGFR-driven STAT3 in U373 glioma cells at 100μM. The ability of chlorpromazine to inhibit the PI3K/mTOR/Akt pathway was similarly tested via western blot, which showed inhibition of phosphorylated Akt and S6 at 10μM. Efficacy of propranolol in perturbing EGFR trafficking was evaluated using flow cytometry and immunofluorescence, which failed to depict altered membrane-associated EGFR abundance. Finally, concentration-dependent inhibition of colony formation was tested for all four drugs. Propranolol and minocycline showed potential biphasic stimulatory effects at 10μM, but all drugs inhibited cell growth at 50μM and higher. Efficacy of these drugs in the treatment of GBM is being further evaluated using in vitro neurosphere cultures from patients identified as having the cellular vulnerabilities potentially targeted by these drugs. Successful completion of this project will lead to in vivo efficacy testing of these four drugs in orthotopic GBM PDX models.