WUSTL Campus Zero-Waste Strategy WashU Waste System Assessment & Zero Waste Planning

WUSTL Campus Zero-Waste Strategy WashU Waste System Assessment & Zero Waste Planning for Sustainability Exchange, Washington University in St. Louis, Spring 202

The effects of yam gruel on lowering fasted blood glucose in T2DM rats

© 2020 Xinjun Lin et al., published by De Gruyter 2020. There is increasing evidence of the linkage between type 2 diabetes mellitus (T2DM) and gut microbiota. Based on our previous studies, we investigated the hypoglycemic mechanisms of yam gruel to provide a scientific basis for its popularization and application. Wistar rats were randomly divided into control and T2DM model groups. Rats in the model group were stimulated by a high-sugar/high-fat diet combined with an intraperitoneal injection of streptozotocin to induce T2DM. The T2DM rats were further subdivided randomly into three groups: (1) DM, (2) DM + yam gruel, and (3) DM + metformin. After 4 weeks of intervention, the changes in gut microbiota, short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), the expression of G protein-coupled receptor 43 (GPR43), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and fasted blood glucose (FBG) levels were observed. Yam gruel intervention elevated the abundance of probiotic bacteria and increased the expression of SCFAs, GPR43 receptor, GLP-1, and PYY. It also reduced FBG levels. We conclude that yam gruel can lower FBG by promoting the growth of probiotic bacteria, increasing the content of SCFAs, and enhancing the expression of GPR43 receptor to increase the content of GLP-1 and PYY in serum

Effects of Dioscorea polystachya \u27yam gruel\u27 on the cognitive function of diabetic rats with focal cerebral ischemia-reperfusion injury via the gut-brain axis

© 2020 Pang et al. Published by IMR press. Focal cerebral ischemia-reperfusion injury is closely related to hyperglycemia and gut microbiota imbalance, while gut microbiota contributes to the regulation of brain function through the gut-brain axis. Previous studies in patients with diabetes have found that \u27yam gruel\u27 is a classic medicated diet made from Dioscorea polystachya, increases the content of Bifidobacterium, regulates oxidative stress, and reduces fasting blood glucose levels. The research reported here investigated the effects of \u27yam gruel\u27 on the cognitive function of streptozotocin-induced diabetic rats with focal cerebral ischemia-reperfusion injury and explored the mechanism underlying the role of the gut-brain axis in this process. \u27Yam gruel\u27 was shown to improve cognitive function as indicated by increased relative content of probiotic bacteria, and short-chain fatty acids in the intestinal tract and cerebral cortex reduced oxidative stress and inflammatory response and promotion of the expression of neurotransmitters and brain-derived neurotrophic factor. Thus, it is concluded that \u27yam gruel\u27 has a protective effect on cognitive function via a mechanism related to the gut-brain axis

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopaedic devices. In this study, the FDA approved plastic polycaprolactone, was embossed with nanometric grooves and the response of primary and immortalised osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion, they formed more focal complexes and a lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalised cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin mediated FAK activation

Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and nonallergic children

Background Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts. Methods We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. Results A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). Conclusions This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways

Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR

Purpose: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mTOR for the treatment of HCC. However, such inhibitors induce hyperglycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor phenformin could reverse both side effects, impose an energetic stress on cancer cells, and suppress the growth of HCC. Experimental Design: Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated preclinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. Results: We found phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with phenformin, was highly efficacious in controlling tumor burden. However, more strikingly, pretreatment with phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Conclusions: Treatment of HCC cells in vitro with the biguanide phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC

Understanding the attitudes of the elderly towards enrolment into cancer clinical trials

BACKGROUND: The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials. This project focuses on the attitudes of the elderly about participation in clinical trials to determine if this is one of the barriers to the involvement of this population in clinical trials. METHODS: The first phase of this study was a self-administered questionnaire mailed to 425 elderly persons with cancer, selected from Princess Margaret Hospital oncology clinics. The second phase consisted of individual semi-structured interviews with cancer patients to assess their attitudes towards cancer, its management and enrolment into cancer clinical trials. RESULTS: Ninety-four patients responded to the survey giving a response rate of 22.1%. Three quarters of respondents stated that they would be willing to participate in a clinical trial. The factors that most influenced older patients' willingness to participate in a cancer study were recommendations from a cancer doctor and the chance that the study treatment may help them feel better. Seventeen survey responders participated in interviews. Common themes from these interviews included patient-physician communication, the referral process, and the role of age in cancer care decision-making. CONCLUSION: Most elderly people, who responded to this survey, are willing to consider participation in cancer clinical trials however, elderly patients do not appear to actively seek clinical trials and few were informed of the availability of clinical trials. Physician barriers and availability of appropriate clinical trials may play a bigger role in preventing accrual of elderly cancer patients into trials

international Epidemiology of Carbapenemase-Producing Escherichia Coli

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. CONCLUSIONS: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations

The effect of organoclay addition on the properties of an acrylate based, thermally activated shape memory polymer

Shape Memory Polymers (SMPs) exhibit the intriguing ability to change back from an intermediate, deformed shape back to their original, permanent shape. In this contribution a systematic series of t-butylacrylate-co-poly(ethyleneglycol) dimethacrylate (tBA-co-PEGDMA) polymers have been synthesised and characterised prior to incorporation of organoclay. Increasing the poly(ethyleneglycol) dimethacrylate (PEGDMA) content in increments of 10% increased the storage modulus from 2005 to 2250 MPa, reduced the glass transition temperature from + 41 to − 26 °C and reduced the intensity of the associated tan δ peak. The tBA-co-PEGDMA crosslinked networks displayed useful shape memory properties up to PEGDMA contents of 40%. Above this PEGDMA percentage the materials were prone to fracture and too brittle for a realistic assessment of their shape memory capability. The system containing 90% t-butylacrylate (tBA) and 10% PEGDMA was selected as the host matrix to investigate how the incorporation of 1 to 5 mass% of a benzyl tallow dimethylammonium-exchanged bentonite (BTDB) influenced the shape memory properties. X-ray diffraction data confirmed that BTDB formed a microcomposite in the selected matrix and exerted no influence on the storage modulus, rubbery modulus, glass transition temperature, Tg, or the shape or intensity of the tan δ peak of the host matrix. Therefore, it was anticipated that the presence of BTDB would have no effect, positive or negative, nor on the shape memory properties of the host matrix. However, it was found that the incorporation of clay, especially at the 1 mass% level, significantly accelerated the speed, compared with the clay-free SMP, at which the microcomposite returned to the original, permanent shape. This accelerated return to the permanent shape was also observed when the microcomposite was coated onto a 100 μm PET film