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Open Access Publications from the University of California

Scholarly Works (16 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2014)

Artificial lipid bilayers have many uses. They are well established for scientific studies of reconstituted ion channels, used to host engineered pore proteins for sensing, especially DNA sequencing, and can potentially be applied in nanoparticle toxicity screening. To better explore these applications, we have simplified the formation and electrical measurement of the traditional method using an apparatus that only requires fluid dispensation. We achieved simultaneous bilayer formation and measurement over a 32-element array with ~80% yield and no operator input following fluid addition. Cycling these arrays resulted in the formation and measurement of 96 out of 120 possible bilayers in 80 minutes, a sustainable rate that could significantly increase with automation and greater parallelization. We have also used this bilayer array platform to study nanoparticles. The platform was validated for this purpose through probing the interaction between amine or carboxyl modified polystyrene nanoparticles and bilayers in conditions of different ionic strength, particle concentration, bilayer charge, and pH. We discovered that NH2-NP ruptures bilayers by generating either transient or persistent pores on bilayers. Furthermore, we conducted nanoparticle toxicity screening with our bilayer array platform. For the first time we identified that CeO2, Co3O4, and In2O3 can damage lysosomal membranes, and that Fe3O4, HfO2, and TiO2 cannot. Our platform confirmed that ZnO, C60, CuO, Er2O3, Eu2O3, La2O3, and Gd2O3 disrupt lipid bilayers. The data from our bilayer array platform also indicated that the ability of nanoparticles to destruct membranes largely depends on the surface coating. In general, positive coating makes the particles more potent to membranes, and negative coating makes the particles safer. Our results about nanoparticles' ability to rupture bilayers are highly correlated with the cytotoxicity data in the literature. Therefore, our bilayer array platform has a great potential of being used for nanoparticle toxicity screening.

    Cover page: Develop an artificial lipid bilayer array platform and screen nanoparticle-membrane interactions
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2017)
    Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments.
      Cover page: Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2020)

      Background

      Diabetes mellitus (DM) is considered a cardiovascular risk factor. The aim of this study was to analyze the prevalence and volume of coronary artery plaque in patients with diabetes mellitus (DM) vs. those without DM.

      Methods

      This study recruited consecutive patients who underwent coronary computed tomography (CT) angiography (CCTA) between October 2016 and November 2017. Personal information including conventional cardiovascular risk factors was collected. Plaque phenotypes were automatically calculated for volume of different component. The volume of different plaque was compared between DM patients and those without DM.

      Results

      Among 6381 patients, 931 (14.59%) were diagnosed with DM. The prevalence of plaque in DM subjects was higher compared with nondiabetic group significantly (48.34% vs. 33.01%, χ = 81.84, P < 0.001). DM was a significant risk factor for the prevalence of plaque in a multivariate model (odds ratio [OR] = 1.465, 95% CI: 1.258-1.706, P < 0.001). The volume of total plaque and any plaque subtypes in the DM subjects was greater than those in nondiabetic patients significantly (P < 0.001).

      Conclusion

      The coronary artery atherosclerotic plaques were significantly higher in diabetic patients than those in non-diabetic patients.
        Cover page: Quantification of atherosclerotic plaque volume in coronary arteries by computed tomographic angiography in subjects with and without diabetes
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2019)
          Cover page: Is waist-to-height ratio better than body mass index as a predictive indicator of coronary atherosclerosis disease? A cohort study
          • Article
          • Peer Reviewed
          UC Riverside Previously Published Works (2024)
          Hallmarks of the developmental cycle of the obligate intracellular pathogenic bacterium Chlamydia are the primary differentiation of the infectious elementary body (EB) into the proliferative reticulate body (RB) and the secondary differentiation of RBs back into EBs. The mechanisms regulating these transitions remain unclear. In this report, we developed an effective novel strategy termed dependence on plasmid-mediated expression (DOPE) that allows for the knockdown of essential genes in Chlamydia. We demonstrate that GrgA, a Chlamydia-specific transcription factor, is essential for the secondary differentiation and optimal growth of RBs. We also show that GrgA, a chromosome-encoded regulatory protein, controls the maintenance of the chlamydial virulence plasmid. Transcriptomic analysis further indicates that GrgA functions as a critical regulator of all three sigma factors that recognize different promoter sets at developmental stages. The DOPE strategy outlined here should provide a valuable tool for future studies examining chlamydial growth, development, and pathogenicity.
            Cover page: Requirement of GrgA for Chlamydia infectious progeny production, optimal growth, and efficient plasmid maintenance.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2016)

            Background

            Surveys that describe the utilization of cardiac CT are available for the United States, Germany, and Taiwan, but not mainland China.

            Objectives

            To analyze the clinical utilization of cardiac CT in mainland China.

            Methods

            A 25-item questionnaire was created and 240 tertiary hospitals were randomly selected to participate. Survey data were collected and confirmed by email as well as phone interviews.

            Results

            In total, 237 (99%) hospitals consented to this survey, but 85 were excluded because of lack of cardiac CT patient volume or advanced technology. Finally, 152 (64%) questionnaires were available for analysis. Median patient volume was 1,037 patients (range: 150-8,072) annually. The most common clinical indications for coronary CT angiography were exclusion of coronary artery disease in patients with low to intermediate pretest likelihood, asymptomatic individuals with cardiovascular risk factors, and follow-up after coronary bypass grafting. The median heart rate threshold for beta blocker administration was >70 beats/min; most centers (86%) used sublingual nitroglycerin. Prospectively ECG triggered acquisition was the predominant technique in 44% of hospitals. Most (59%) providers adjusted the tube current to the body mass, but few (16%) adjusted the contrast injection rate. Per case, the mean examination duration was 14.2 min; post-processing time 13.6 min; and reporting time 18.0 min.

            Conclusions

            Cardiac CT is widely established in clinical practice in mainland China but there is a need for more uniform standards regarding performance and clinical utilization.
              Cover page: Current utilization of cardiac computed tomography in mainland China: A national survey
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2019)
              Importance:Epidemiologic evidence of the mechanisms of the association between long-term exposure to air pollution and coronary heart disease (CHD) is limited and relies heavily on studies performed in Europe and the United States, where air pollution levels are relatively low. In particular, the association between air pollution and CHD in patients with underlying risks for CHD is understudied. Objective:To determine whether air pollution and proximity to traffic are associated with the coronary artery calcium (CAC) score, a key atherosclerotic marker. Design, Setting, and Participants:In this prospective, population-based cross-sectional study in a large-scale setting in China, 8867 consecutive patients aged 25 to 92 years with suspected CHD were recruited between November 17, 2015, and September 13, 2017. Participants were excluded if they had previous myocardial infarction, stenting, or coronary artery bypass grafting or incomplete risk factors and exposure data. Each participant underwent assessment of CAC and CHD risk factors at baseline. Data were analyzed from December 2017 to November 2018. Exposures:Annual means of fine particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were estimated at the participants' residences using a validated geostatistical prediction model. Exposure to a nearby roadway was also estimated. Main Outcomes and Measures:Computed tomography measurement of CAC score. Results:The mean (SD) age of the 8867 participants was 56.9 (10.4) years; 4378 (53.6%) were men. Annual mean (SD) PM2.5, NO2, and O3 measurements were 70.1 (20.0), 41.4 (14.7), and 93.9 (10.5) μg/m3, respectively. The mean (SD) CAC score was 91.4 (322.2) Agatston units. Exposure to PM2.5 and NO2, adjusting for CHD risk factors and multiple pollutants, were independently associated with increases in CAC scores of 27.2% (95% CI, 10.8% to 46.1%) per 30 μg/m3 PM2.5 and 24.5% (95% CI, 3.6% to 49.7%) per 20 μg/m3 NO2. For PM2.5, odds of both detectable CAC (Agatston score >0; odds ratio, 1.28; 95% CI, 1.13 to 1.45) and severe CAC (Agatston score >400; odds ratio, 1.59; 95% CI, 1.20 to 2.12) were increased. Associations of CAC with PM2.5 and NO2 were greater among male participants (PM2.5: 42.2%; 95% CI, 24.3% to 62.7%; NO2: 45.7%; 95% CI, 25.3% to 69.5%) and elderly participants (PM2.5: 50.1%; 95% CI, 28.8% to 75.0%; NO2: 55.5%; 95% CI, 31.8% to 83.6%) and those with diabetes (PM2.5: 62.2%; 95% CI, 30.9% to 101.0%; NO2: 31.2%; 95% CI, 13.9% to 51.0%). Independent association with CAC score was 9.0% (95% CI, -1.4% to 20.4%) for O3 per 15 μg/m3 and 2.4% (95% CI, -0.6% to 5.4%) for distance near roadway per 50% decrease. Conclusions and Relevance:In this large Chinese study, long-term exposures to PM2.5 and NO2 were independently associated with severity of CAC. This finding may provide support for the pathophysiological role of coronary atherosclerosis through which air pollution exposure may be associated with CHD.
                Cover page: Association of Estimated Long-term Exposure to Air Pollution and Traffic Proximity With a Marker for Coronary Atherosclerosis in a Nationwide Study in China
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2019)
                Retinal degenerative diseases lead to blindness with few treatments. Various cell-based therapies are aimed to slow the progression of vision loss by preserving light-sensing photoreceptor cells. A subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rat model of retinal degeneration has aided in photoreceptor survival, though the mechanisms are mainly unknown. Identifying the retinal proteomic changes that occur following hNPC treatment leads to better understanding of neuroprotection. To mimic the retinal environment following hNPC injection, a co-culture system of retinas and hNPCs is developed. Less cell death occurs in RCS retinal tissue co-cultured with hNPCs than in retinas cultured alone, suggesting that hNPCs provide retinal protection in vitro. Comparison of ex vivo and in vivo retinas identifies nuclear factor (erythroid-derived 2)-like 2 (NRF2) mediated oxidative response signaling as an hNPC-induced pathway. This is the first study to compare proteomic changes following treatment with hNPCs in both an ex vivo and in vivo environment, further allowing the use of ex vivo modeling for mechanisms of retinal preservation. Elucidation of the protein changes in the retina following hNPC treatment may lead to the discovery of mechanisms of photoreceptor survival and its therapeutic for clinical applications.
                  Cover page: In Vitro and In Vivo Proteomic Comparison of Human Neural Progenitor Cell‐Induced Photoreceptor Survival
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2011)
                  Background

                  The incidence of coronary heart disease (CHD) is higher in Northern than that in Southern China, however differences in traditional CHD risk factors do not fully explain this. No study has examined the differences in subclinical atherosclerosis that may help explain the differences in incidence. This study examined these differences in subclinical atherosclerosis using coronary computed tomography (CT) for calcification between the Northern and Southern China.

                  Methods

                  We selected a random sample of participants in a large multi-center ongoing epidemiologic study for coronary calcium scanning in one northern city (North) (Beijing, n = 49) and in two southern cities (South) (Shanghai, n = 50, and Guangzhou, n = 50). Participants from the three field centers (mean age 67 years) underwent coronary risk factor evaluation and cardiac CT scanning for coronary calcium measurement using the Multi-Ethnic Study of Atherosclerosis scanning protocol.

                  Results

                  Adjusted log-transformed coronary artery calcium score in North China (Beijing) was 3.1 ± 0.4 and in South China (Shanghai and Guangzhou) was 2.2 ± 0.3 (P = 0.04). Mean calcium score for the northern city of Beijing was three times higher than that of the southern city of Guangzhou (P = 0.01) and 2.5 times higher than for the southern city of Shanghai (P = 0.03).

                  Conclusions

                  The extent of subclinical atherosclerosis is significantly higher in the northern city of Beijing than that in the two southern cities of Guangzhou and Shanghai, even after adjusting for standard cardiac risk factors. This finding suggests that standard risk factors do not fully explain north south differences in clinical CHD incidence.

                    Cover page: Subclinical atherosclerosis in northern and southern China: the Chinese paradox
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2013)

                    Little is known about the influence of metabolic syndrome (MetS) on coronary artery calcification (CAC) in China. In this article, we aimed to explore the distribution of CAC in populations with and without MetS, and estimate the influence of MetS and its components on CAC in a community-based population of Beijing.

                    A total of 1647 local residents of Beijing, age 40-77 years, were recruited for a cardiovascular risk factors survey and were determined fasting plasma glucose (FPG), blood lipids, and 64 multi-detector computed tomography (64-MDCT) coronary artery calcium score (CACS) measurement (Agatston scoring). The distribution of CAC was described, and the influence of MetS components on CAC was evaluated.

                    In this population, the prevalence and extent of CAC increased with increasing age and both were higher in MetS subjects compared to nonMetS subjects (all P < 0.05), with the exception of those older than 65 years old. The risk of CAC increased with increasing numbers of MetS components, and the odds ratios for predicting positive CAC in subjects with 1, 2, 3, and = 4 MetS components were 1.60, 1.84, 2.12, and 3.12, respectively (all P < 0.05). Elevated blood pressure, elevated FPG, elevated triglycerides, and overweight increased the risk of CAC, yielding odds ratios of 2.64, 1.67, 1.32, and 1.37, respectively (all P < 0.05).

                    In the Beijing community-based population, MetS increases the risk of CAC. The risk of CAC increases with increasing numbers of MetS components. Not only the number, but also the variety of risk factors for MetS is correlated with the risk of CAC. Elevated blood pressure, hyperglycemia, hypertriglyceridemia and overweight increase the risk of CAC.

                      Cover page: Metabolic syndrome and coronary artery calcification: a community-based natural population study.Creative Commons 'BY' version 4.0 license
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