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Bioactive hydrogel microcapsules for guiding stem cell fate decisions by release and reloading of growth factors

Bioactive Materials 2022年第9期7卷 1-14页

作者： Kihak Gwon Hye Jin Hong Alan M.Gonzalez-Suarez Michael Q.Slama Daheui Choi Jinkee Hong Harihara Baskaran gulnaz stybayeva Quinn P.Peterson Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMN55902USA Department of Chemical and Biomolecular Engineering Yonsei UniversitySeoul03722Republic of Korea Department of Chemical and Biomolecular Engineering Case Western Reserve UniversityClevelandOH44106USA

Human pluripotent stem cells(hPSC)hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure.Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols.In this paper,we sought to address these challenges through the development of bioactive microcapsules.A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell.Importantly,the shell contained heparin moieties for growth factor(GF)binding and release.The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation.Specifically,we demonstrated that one-time,1 h long loading of pluripotency signals,fibroblast growth factor(FGF)-2 and transforming growth factor(TGF)-β1,into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs.Furthermore,stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue,Nodal,resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol.Overall,bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.

关键词： Droplet microfluidics Bioactive core-shell microcapsule Growth factor release 3D stem cell culture Stem cell differentiation

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Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor

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Bioactive Materials 2023年第10期28卷 183-195页

作者： Kihak Gwon Daheui Choi Jose Mde Hoyos-Vega Harihara Baskaran Alan M.Gonzalez-Suarez Seonhwa Lee Hye Jin Hong Kianna M.Nguyen Ether Dharmesh Go Sugahara Yuji Ishida Takeshi Saito gulnaz stybayeva Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMNUSA Department of Chemical and Biomolecular Engineering Case Western Reserve UniversityClevelandOHUSA Biomedical Engineering Saint Louis UniversitySt.LouisMOUSA University of Southern Californi1 Keck School of MedicineDepartment of MedicineDivision of Gastrointestinal and Liver DiseasesLos AngelesCAUSA Research and Development Department PhoenixBioCo.LtdKagamiyam1Higashi-Hiroshim1Hiroshim1Japan USC Research Center for Liver Diseases Los AngelesCAUSA

The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue engineering.Several approaches can be used to restore hepatocyte function in vitro,including coating a culture substrate with extracellular matrix(ECM),encapsulating cells within biomimetic gels(Collagen-or Matrigel-based),or co-cultivation with other cells.This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids.These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors.We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes.We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor(HGF)into microcapsules and inhibiting transforming growth factor(TGF)-β1 signaling.Overall,bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering,regenerative medicine,and drug testing applications.

关键词： Droplet microfluidics Bioactive microcapsules Hepatocyte spheroid Heparin Hepatocyte growth factor

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A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies

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Microsystems & Nanoengineering 2020年第1期6卷 315-326页

作者： Neda Dadgar Alan M.Gonzalez-Suarez Pouria Fattahi Xiaonan Hou John S.Weroha Alexandre Gaspar-Maia gulnaz stybayeva Alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMN 55905USA Department of Medical Oncology Mayo ClinicRochesterMN 55905USA Department of Laboratory Medicine and Pathology Mayo ClinicRochesterMN 55905USA

There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer.Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants.However,standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process.Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements.This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids.Six patient-derived xenograft(PDX)tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures.To further demonstrate the potential for miniaturization and multiplexing,we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations.These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device.Overall,we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device.This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited,such as following the acquisition of biopsy specimens obtained by fine-needle aspiration.

关键词： testing fluid cancer

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Detecting cell-secreted growth factors in microfluidic devices using bead-based biosensors

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Microsystems & Nanoengineering 2017年第1期3卷 242-250页

作者： Kyung Jin Son Pantea Gheibi gulnaz stybayeva Ali Rahimian Alexander Revzin Department of Biomedical Engineering University of CaliforniaDavisCalifornia 95616USA Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMinnesota 55905USA

Microfluidic systems provide an interesting alternative to standard macroscale cell cultures due to the decrease in the number of cells and reagents as well as the improved physiology of cells confined to small volumes.However,the tools available for cell-secreted molecules inside microfluidic devices remain limited.In this paper,we describe an integrated microsystem composed of a microfluidic device and a fluorescent microbead-based assay for the detection of the hepatocyte growth factor(HGF)and the transforming growth factor(TGF)-β1 secreted by primary hepatocytes.This microfluidic system is designed to separate a cell culture chamber from sensing chambers using a permeable hydrogel barrier.Cell-secreted HGF and TGF-β1 diffuse through the hydrogel barrier into adjacent sensing channels and are detected using fluorescent microbead-based sensors.The specificity of sensing microbeads is defined by the choice of antibodies;therefore,our microfluidic culture system and sensing microbeads may be applied to a variety of cells and cell-secreted factors.

关键词： biosensors growth factors microbead microchamber primary hepatocytes

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Comprehensive Dynamics of Banking: A Systemic Approach Incorporating Lending, Investment, and Capital Variables

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Journal of Systems Science and Information 2024年

作者： gulnaz ABDUKADYROVA Adilia TABYSHOVA Minara NAZEKOVA Jyldyz ALYMBAEVA Cholpon TOKTOSUNOVA Department of Banking and the Securities Market Musa Ryskulbekov Kyrgyz Economic University Department of Finance and Financial Technologies named after S.A.Sulaymanbekov Musa Ryskulbekov Kyrgyz Economic University

The research topic related to the analysis of banking activity is relevant since the banking sector is complex and dynamic and requires constant monitoring and analysis to make informed decisions. Using a mathematical model of system dynamics to analyse banking activities can help banks make better decisions, manage risk, ensure the stability and efficiency of operations, and adapt to changing conditions. The purpose of the study is to determine the influence of various factors, in particular economic activity, on the final profit of the bank. Among the methods used, the analytical method, the functional method, the system analysis method, the deduction method, the synthesis method, and the comparison method were applied. In the course of this study, an extensive analytical review of banking activities was carried out using a system dynamics model, taking into account the requirements of the International Financial Reporting Standards(IFRS 9). The study included various scenario analyses to explore the impact of changes in economic conditions on the bank’s loan portfolio,risk level, and profitability. Both economic growth scenarios and recession scenarios were considered in order to more fully assess their impact on the financial condition of the bank. A forecast and analysis of the risks associated with lending, investments, and other bank operations was carried out. The practical significance lies in the application of the results obtained to address issues related to banking in order to increase the efficiency of this process and achieve a new level of development.

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Modeling and Simulation of Heterojunction Solar Cell with Mono Crystalline Silicon

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Journal of Applied Mathematics and Physics 2024年第3期12卷 997-1020页

作者： Sajid Ullah Ayesha gulnaz Guangwei Wang School of Electronic Engineering Tianjin University of Technology and Education Tianjin China Department of Physics Rihah International University Islamabad Pakistan

The monocrystalline silicon is a promising material that could be used in solar cells that convert light into electricity. Although the cost of ordinary silicon (Si) solar cells has decreased significantly over the past two decades, the conversion efficiency of these cells has remained relatively high. While solar cells have a great potential as a device of renewable energy, the high cost they incur per Watt continues to be a significant barrier to their widespread implementation. As a consequence, it is vital to conduct research into alternate materials that may be used in the construction of solar cells. The heterojunction solar cell (HJSC), which is based on n-type zinc oxide (n-ZnO) and p-type silicon (p-Si), is one of the numerous alternatives of the typical Si single homojunction solar cell. There are many deficiencies that can be found in the published research on n-ZnO/p-Si heterojunction solar cell. Inconsistencies in the stated value of open circuit voltage (Voc) of the solar cell are one example of deficiency. The absence of a full theoretical study to evaluate the potential of the solar cell structure is another deficiency that can be found in these researches. A lower value of experimentally obtained VOC in comparison to the theoretical prediction based on the band-gap between n-ZnO and p-Si. There needs to be more consensus among scientists regarding the optimal conditions for the growth of zinc oxide. Many software’s are available for simulating and optimizing the solar cells based on these parameters. For this purpose, in this dissertation, I provide computational results relevant to n-ZnO/p-Si HJSC to overcome deficiencies that have been identified. While modeling and simulating the potential of the solar cell structure with AFORS-HET, it is essential to consider the constraints that exist in the real world. AFORS-HET was explicitly designed to mimic the multilayer solar cell arrangement. In AFORS-HET, we can add up to seven layers for solar cell layout. By using this softwa

关键词： Heterojunction Solar Cell Silicon Monocrystalline Deficiencies AFORS-HET Optimization Open Circuit Voltage Quantum Efficiency

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Tolerance effects of non-steroidal anti-inflammatory drugs microinjected into central amygdala,periaqueductal grey,and nucleus raphe Possible cellular mechanism

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Neural Regeneration Research 2012年第13期7卷 1029-1039页

作者： Merab G.Tsagareli Nana Tsiklauri Ivliane Nozadze gulnaz Gurtskaia Ivane Beritashvili Experimental BioMedicine Center Tbilisi 0160Georgia

Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs （NSAIDs）, or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic （intraperitoneal） administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.

关键词： Analgesia antinociception descending pain modulation hot plate test non-opioid tolerance non-steroidal anti-inflammatory drugs tail-flick reflex neural regeneration

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Flavonoids and Amino Acids Analysis of the Fruits of Cornus mas L. Introduced in Uzbekistan

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American Journal of Plant Sciences 2023年第9期14卷 1075-1084页

作者： gulnaz Matkarimova Nodira Nurullayeva Khislat Khaydarov Department of Medical Biology and Genetics Samarkand State Medical University Samarkand Uzbekistan Department of Botany Samarkand State University Samarkand Uzbekistan

Cornelian cherry is used in the food and pharmaceutical industry as an ornament, in traditional medicine, and in the manufacture of household items. It is widely used in medicine for the prevention and treatment of many diseases. Therefore, it is important to research the chemical composition of these species. In the article, based on our research, the analysis of the quantitative calculation of flavonoids and amino acids of the fruits of the “Elegant” and “Svetlyachok” cherry varieties was carried out. It was found that the amount of amino acids in the fruits of Cornus mas L., introduced in Uzbekistan, is higher in the variety “Svetlyachok” 2.643235 mg/g. In “Elegant” variety it was 1.794235 mg/g. The amount of 4 different flavonoids in the fruit was also determined. It has been established that the Elegant variety has a high concentration of lutein and rutin, and the svetlyachok has a high concentration of apigenin and quercetin.

关键词： Cornus mas L. Medicinal Amino Acid Composition Flavonoids Fruits

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Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2011年第32期17卷 3745-3751页

作者： Ilyar Sheyhidin gulnaz Nabi Ayshamgul Hasim Rui-Ping Zhang Julaiti Ainiwaer Hong Ma Hua Wang Department of Thoracic Surgery of the First Affiliated Hospital Medical University of Xinjiang 830054 Urumqi Xinjiang China Department of Rehabilitative of the First Affiliated Hospital Medical University of Xinjiang 830054 Urumqi Xinjiang China Department of Pathology College of Basic Medicine Medical University of Xinjiang 830011 Urumqi Xinjiang China

AIM: To investigate the expression of Toll-like receptor (TLR) 3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma (ESCC). METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression of TLR3, TLR4, TLR7 and TLR9 mRNA and protein in samples from 87 esophageal cancer patients consisting of both tumor and normal tissue. RESULTS: A significant increase in TLR3, TLR4, TLR7 and TLR9 mRNA levels was detected in ESCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR3, TLR4, TLR7 and TLR9, respectively, P < 0.05). Nevertheless, a significant percentage of tumors also exhibited TLR4 expression in mononuclear inflammatory cells (48.3%) and TLR9 expression in fibroblast-like cells (60.9%). Tumors with high TLR3 expression in tumor cells or high TLR4 expression in mononuclear inflammatory cells were significantly associated with a higher probability of lymph node metastasis and increased depth of invasion. However, tumors with high TLR9 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR3, TLR4, TLR7 and TLR9 among different ethnic groups. CONCLUSION: TLR3, TLR4, TLR7 and TLR9 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for ESCC.

关键词：鳞状细胞癌 TLR4 TLR9 食管癌过表达 Toll样受体肿瘤细胞聚合酶链反应

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Online Teaching Experience during the COVID-19 in Pakistan:Pedagogy-Technology Balance and Student Engagement

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Fudan Journal of the Humanities and Social Sciences 2021年第3期14卷 367-391页

作者： Tayyaba Abid gulnaz Zahid Naseem Shahid Maham Bukhari Applied and Behavioral Training Institute DubaiUnited Arab Emirates School of Social Sciences and Humanities National University of Sciences and Technology.H-12 CampusIslamabadPakistan Centre for Creative Economy National University of Sciences and Technology.H-12 CampusIslamabadPakistan

This study aimed to explore the lived experiences of university teachers who participated in online teaching for the first time during the COVID-19 pandemic.A qualitative method of data collection and inductive thematic analysis were used.The data were collected through a semistructured interview from 11 faculty members who teach in various universities in Pakistan.The analysis presented five themes of the online teaching experience:culture and gender-related issues,teaching effectiveness,challenges in online teaching,coping strategies,and faculty's'post-COVID-19 perceptions.The findings reflect that the faculty prioritized to focus on immediate online instructional matters in the wake of the pandemic with a lack of emphasis on global practices for online learning.Experienced and young faculty reported disparities in striking a balance between pedagogy and technology.Moreover,despite the limitations,the experience itself prepared the faculty for a blended learning approach and increased their awareness of global and future challenges.The implications were reported based on the findings.

关键词： Online teaching Higher education Teaching effectiveness Stress Global concerns

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