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Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes

International Journal of Biological Macromolecules 2024年第Part1期275卷 133467页

作者： Chen, Huai-An Tai, Yi-Ning Hsieh, Erh-Hsuan Thacker, Minal Lin, I-Chan Tseng, Ching-Li Lin, Feng-Huei Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Shuang-Ho Campus New Taipei City Taiwan Institute of Biomedical Engineering College of Medicine & College of Engineering National Taiwan University Taipei City Taiwan 17W Hong Kong Science Park Hong Kong Department of Ophthalmology Wan Fang Hospital Taipei Medical University Taipei City Taiwan Department of Ophthalmology School of Medicine College of Medicine Taipei Medical University Taipei City Taiwan International Ph. D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Shuang-Ho Campus New Taipei City Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei City Taiwan International Ph. D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei City Taiwan National Health Research Institutes Miaoli County Taiwan

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the physical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for ophthalmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 μM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BDDE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively. © 2024 The Authors

关键词： Hyaluronic acid

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Hellebrigenin induces oral cancer cell apoptosis by modulating MAPK signalling and XIAP expression

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Journal of Cellular and Molecular medicine 2024年第2期28卷 e18071-e18071页

作者： Hsieh, Ming-Ju Lin, Chia-Chieh Lo, Yu-Sheng Ho, Hsin-Yu Chuang, Yi-Ching Chen, Mu-Kuan Oral Cancer Research Center Changhua Christian Hospital Changhua Taiwan Doctoral Program in Tissue Engineering and Regenerative Medicine College of Medicine National Chung Hsing University Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Department of Otorhinolaryngology Head and Neck Surgery Changhua Christian Hospital Changhua Taiwan

Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced-stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle-related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl-2 and Bcl-xL) and upregulation of pro-apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase-mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro-apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC. © 2023 The Authors. Journal of Cellular and Molecular medicine published by Foundation for Cellular and Molecular medicine and John Wiley & Sons Ltd.

关键词： apoptosis hellebrigenin oral squamous cell carcinoma XIAP

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Development and application of the electrospun Microtube Array Membrane (MTAM) substrate as a potential drug encapsulation platform for continuous drug release platform for treatment of Elevated intraocular pressure (IOP) in glaucoma disease

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Polymer 2025年 333卷

作者： Huang, Jou-Chen Lee, Ching-Yu Chew, Chee Ho Huang, Wan-Ting Chang, Shun-Chieh Chen, Chien-Chung Department of Ophthalmology Taipei Medical University Hospital Taipei Taiwan Department of Ophthalmology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Orthopedics Taipei Medical University Hospital Taipei Taiwan Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei 11052 Taiwan for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan The PhD Program for Translational Medicine Taipei Medical University Taipei 11052 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 110 Taiwan Ph.D Program in Biotechnology Research and Development College of Pharmacy Taipei Medical University Taipei 110 Taiwan

Glaucoma is the leading cause of blindness which is characterized by the elevation of intraocular pressure (IOP) which results in optic nerve damage. Clinically, the current mainstay of treatment which involves the use of anti-glaucoma agents delivered in the form of topical eye drops have limitations such as short drug retention times, pulsatile delivery and localized adverse effects. In this work, we strive to demonstrate the development of a novel drug encapsulation device, known as Microtube Array Membrane (MTAM) as a potential substrate for encapsulation of clinically available anti-glaucoma agent that is based on the materials Polysulfone (PSF) and poly(lactic acid) (PLA) and poly(glycolic acid) (PLA-PLGA) copolymer. The resulting MTAM variants demonstrated tunable microstructures, mechanical properties and drug release;where pore sizes ranging from from 0.24 ± 0.02 μm to 17.62 ± 4.62 μm was successfully fabricated, and with loading efficiency of Brimonidine Tartrate up to 90 %. Sustained drug release was observed over 3 days under simulated tear physiological conditions, with the PLA-PLGA MTAM variants released the greatest amount of drug encapsulated within and sustained even in the presence of simulated tears turnover. Critically, the encapsulation of the drug within the respective MTAMs seemed to mitigate any toxicity effects that was largely reported in direct use of Brimonidine Tartrate. Potentially, with more research and development, the MTAM based drug encapsulation could effective be deployed as a novel drug release system in future localized and sustained drug delivery. © 2025

关键词： Elevated intraocular pressure Glaucoma Microtube Array membrane Prolonged drug release

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Enhancing wound healing and adhesion through dopamine-assisted gelatin-silica hybrid dressings

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International Journal of Biological Macromolecules 2024年第Part2期258卷 128845页

作者： Lin, Yu-Chien Wang, Huey-Yuan Tang, Yao-Chun Lin, Wan-Rong Tseng, Ching-Li Hu, Chih-Chien Chung, Ren-Jei Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei10608 Taiwan School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue Singapore639798 Singapore Department of Stomatology MacKay Memorial Hospital Taipei104217 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph. D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph. D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Bone and Joint Research Center Chang Gung Memorial Hospital Linkou33305 Taiwan Taipei10608 Taiwan

Gelatin, widely employed in hydrogel dressings, faces limitations when used in high fluid environments, hindering effective material adhesion to wound sites and subsequently reducing treatment efficacy. The rapid degradation of conventional hydrogels often results in breakdown before complete wound healing. Thus, there is a pressing need for the development of durable adhesive wound dressings. In this study, 3-glycidoxypropyltrimethoxysilane (GPTMS) was utilized as a coupling agent to create gelatin-silica hybrid (G-H) dressings through the sol-gel method. The coupling reaction established covalent bonds between gelatin and silica networks, enhancing structural stability. Dopamine (DP) was introduced to this hybrid (G-H-D) dressing to further boost adhesiveness. The efficacy of the dressings for wound management was assessed through in-vitro and in-vivo tests, along with ex-vivo bioadhesion testing on pig skin. Tensile bioadhesion tests demonstrated that the G-H-D material exhibited approximately 2.5 times greater adhesion to soft tissue in wet conditions compared to pure gelatin. Moreover, in-vitro and in-vivo wound healing experiments revealed a significant increase in wound healing rates. Consequently, this material shows promise as a viable option for use as a moist wound dressing. © 2023

关键词： Adhesion

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Improvement of clinical wound microcirculation diagnosis using an object tracking-based laser speckle contrast imaging system

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APL Bioengineering 2024年第1期8卷 016105页

作者： Hsieh, Meng-Che Chang, Chia-Yu Hsu, Ching-Han Lin, Yan-Ren Hsieh, Pei-You Ching, Congo Tak-Shing Liao, Lun-De Institute of Biomedical Engineering and Nanomedicine National Health Research Institutes 35 Keyan Road Zhunan Town Miaoli County 35053 Taiwan Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University 145 Xingda Road South District Taichung402 Taiwan Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University No. 101 Section 2 Kuang-Fu Road Hsinchu30013 Taiwan Department of Emergency and Critical Care Medicine Changhua Christian Hospital Changhua Taiwan Graduate Institute of Biomedical Engineering National Chung Hsing University 145 Xingda Road South District Taichung402 Taiwan Department of Electrical Engineering National Chi Nan University 1 University Road Puli Township Nantou County 545301 Taiwan

Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628-0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness. © 2024 Author(s).

关键词： Image enhancement

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Centrifugal Spinning of Porous Polylactic Acid Fibers by Centrifugal Spinning with Phase Separation for Oil Removal Application

SSRN

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SSRN 2024年

作者： Negoro, Masaki Doan, Hoan Ngoc Vo, Phu Phong Khuat, Khanh Van Thi Kinashi, Kenji Sakai, Wataru Tsutsumi, Naoto Master’s Program of Innovative Materials Kyoto Institute of Technology Matsugasaki Sakyo Kyoto606-8585 Japan Tissue Engineering and Regenerative Medicine Laboratory School of Biomedical Engineering International University Vietnam National University Ho Chi Minh City Viet Nam Faculty of Chemistry University of Science Ho Chi Minh City Viet Nam Doctor’s Program of Materials Chemistry Graduate School of Science and Technology Kyoto Institute of Technology Matsugasaki Sakyo Kyoto606-8585 Japan Faculty of Materials Science and Engineering Kyoto Institute of Technology Matsugasaki Sakyo Kyoto606-8585 Japan

Developing biodegradable oil absorption fibrous materials is essential because discarding conventional separation materials could cause secondary pollution due to their nondegradable properties. In this study, highly hydrophobic and superoleophilic porous polylactic acid (PLA) fibers were prepared using centrifugal spinning combined with nonsolvent-induced phase separation. The porous structure of PLA fibers was controlled by the ratio between good solvent and nonsolvent in the spinning solutions. The morphology and physical properties of the obtained PLA fibers were investigated using various measurement techniques. The PLA fibrous membrane prepared from a PLA solution containing chloroform/dimethylformamide (80/20 w/w) indicated not only a high water contact angle but also a high oil sorption value. The porous PLA fibers are a potential candidate for use as green materials for environmental applications. © 2024, The Authors. All rights reserved.

关键词： Spinning (fibers)

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Validating the association of Oxford classification and renal function deterioration among Taiwanese individuals with Immunoglobulin A nephropathy

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Scientific Reports 2023年第1期13卷 1-14页

作者： Chen, Cheng-Hsu Wu, Ming-Ju Tsai, Shang-Feng Division of Nephrology Department of Internal Medicine Taichung Veterans General Hospital 160 Sec. 3 Boulevard Taichung 407 Taiwan Department of Life Science Tunghai University Taichung Taiwan Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Ph. D. Program in Tissue Engineering and Regenerative Medicine College of Medicine National Chung Hsing University Taichung Taiwan

Validation of the Oxford classification (MEST and MEST-C) for Immunoglobulin A nephropathy (IgAN) in the Taiwanese population is lacking. Our study aimed to validate this classification and assess individual lesion impact. We conducted a retrospective cohort study at Taichung Veterans General Hospital, Taiwan (Jan 2011–Jul 2023). Composite renal outcomes were evaluated using clinical conditions and estimated glomerular filtration rate (eGFR). We used Kaplan–Meier, univariable/multivariable logistic regression and ROC curves. Subgroup analysis considered eGFR < or ≥ 30.0 ml/min/1.73 m². In 366 renal biopsies, serum creatinine was 1.34 mg/dl, eGFR 53.8 ml/min/1.73 m², urine protein–creatinine ratio 1159 mg/g. T1/T2 lesions had lowest baseline eGFR (39.6/11.5 ml/min/1.73 m²), correlating with poorest renal survival (median survival 54.7/34.4 months). Univariable analysis linked all individual variables to worse renal outcomes. Multivariable analysis (MEST/MEST-C) showed only T1/T2 linked to worse outcomes. T score had highest predictive power (AUC 0.728, sensitivity 60.2%, specificity 83.6%), with MEST having high AUC (0.758). No extra predictive power was seen transitioning MEST to MEST-C. Subgroup analysis (eGFR < 30.0 ml/min/1.73 m²) associated C1 with improved renal outcomes (odds ratio 0.14, 95% CI 0.03–0.65). T lesion correlated with worse outcomes across subgroups. The T lesion consistently correlated with worse renal outcomes across all groups and baseline statuses. Integrating the C lesion into the transition from MEST to MEST-C did not enhance predictive power. Importantly, the C1 lesion was linked to improved renal outcomes in the eGFR < 30.0 ml/min/1.73 m² subgroup, likely due to treatment effects. © 2023, The Author(s).

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Zwitterionic modified and freeze-thaw reinforced foldable hydrogel as intraocular lens for posterior capsule opacification prevention

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Biomaterials 2024年 309卷 122593-122593页

作者： Yang, Cheng-Jui Huang, Wei-Lun Yang, Yu Kuan, Chen-Hsiang Tseng, Ching-Li Wang, Tzu-Wei Department of Materials Science and Engineering National Tsing Hua University Hsinchu Taiwan Department of Ophthalmology National Taiwan University Hospital Hsin-Cchu Branch Hsinchu Taiwan Interdisciplinary Program of Life Science and Medicine National Tsing Hua University Hsinchu Taiwan Division of Plastic Surgery Department of Surgery National Taiwan University Hospital Taipei Taiwan Graduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei Taiwan Research Center for Developmental Biology and Regenerative Medicine National Taiwan University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei Taiwan

Posterior capsule opacification (PCO) is a predominant postoperative complication, often leading to visual impairment due to the aberrant proliferation and adhesion of lens epithelial cells (LECs) and protein precipitates subsequent to intraocular lens (IOL) implantation. To address this clinical issue, a foldable and antifouling sharp-edged IOL implant based on naturally-derived cellulose hydrogel is synthesized. The mechanical strength and transparency of the hydrogel is enhanced via repeated freeze-thaw (FT) cycles. The incorporated zwitterionic modifications can remarkably prevent the incidence of PCO by exhibiting proteins repulsion and cell anti-adhesion properties. The graft of dopamine onto both the haptic and the periphery of the posterior surface ensures the adhesion of the hydrogel to the posterior capsule and impedes the migration of LECs without compromising transparency. In in vivo study, the zwitterionic modified foldable hydrogel exhibits uveal and capsular biocompatibility synchronously with no signs of inflammatory response and prevent PCO formation, better than that of commercialized and PEG-modified IOL. With foldability, endurability, antifouling effect, and adhesive to posterior capsule, the reported hydrogel featuring heterogeneous surface design displays great potential to eradicate PCO and attain post-operative efficacy after cataract surgery. © 2024 Elsevier Ltd

关键词： Hydrogels

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Large animal models of cardiac ischemia-reperfusion injury:Where are we now?

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Zoological Research 2023年第3期44卷 591-603页

作者： Attaur Rahman Yuhao Li To-Kiu Chan Hui Zhao Yaozu Xiang Xing Chang Hao Zhou Dachun Xu Sang-Bing Ong Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina Centre for Cardiovascular Genomics and Medicine(CCGM) Lui Che Woo Institute Innovative MedicineThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina College of Veterinary Sciences and Animal Husbandry Abdul Wali Khan University MardanMardanKhyber Pakhtunkhwa 23200Pakistan School of Biomedical Sciences CUHK-GIBH CAS Joint Laboratory on Stem Cell and Regenerative MedicineThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina Institute for Tissue Engineering and Regenerative Medicine(iTERM) The Chinese University of Hong Kong(CUHK)Hong Kong SARChina SBS Core Laboratory CUHK Shenzhen Research InstituteShenzhenGuangdong 518172China Kunming Institute of Zoology–The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina Shanghai East Hospital Key Laboratory of Arrhythmias of the Ministry of Education of ChinaSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Guang’anmen Hospital China Academy of Chinese Medical SciencesBeijing 100053China Department of Cardiology Chinese People’s Liberation Army General HospitalBeijing 100853China Center for Cardiovascular Research and Alternative Medicine University of Wyoming College of Health SciencesLaramieWY 82071USA Department of Cardiology Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Hong Kong Hub of Paediatric Excellence(HK HOPE) Hong Kong Children’s Hospital(HKCH)Kowloon BayHong Kong SARChina CUHK Shenzhen Research Institute(SZRI) ShenzhenGuangdong 518172China Neural Vascularand Metabolic Biology Thematic Research ProgramSchool of Biomedical SciencesThe Chinese University of Hong Kong(CUHK)Hong Kong SARChina

Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical ***,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large *** article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.

关键词： Cardiovascular disorder Ischemic cardiac disease Ischemic-reperfusion injury Large animal model Myocardial infarction Translational gap

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Targeting human mitochondrial NAD(P)+-dependent malic enzyme (ME2) impairs energy metabolism and redox state and exhibits antileukemic activity in acute myeloid leukemia

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Cellular Oncology 2023年第5期46卷 1301-1316页

作者： Chen, Kun-Chi Hsiao, I-Hsin Huang, Yu-Nan Chou, Yu-Tung Lin, Yi-Chun Hsieh, Ju-Yi Chang, Yung-Lung Wu, Kang-Hsi Liu, Guang-Yaw Hung, Hui-Chih Department of Life Sciences National Chung Hsing University Taichung Taiwan Ph.D. Program in Tissue Engineering and Regenerative Medicine National Chung Hsing University Taichung Taiwan Department of Biochemistry National Defense Medical Center Taipei Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan Department Pediatrics Chung Shan Medical University Hospital Taichung Taiwan Institute of Medicine College of Medicine Chung Shan Medical University Taichung Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan EGG & Animal Biotechnology Center National Chung Hsing University Taichung Taiwan

Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAD(P)+-dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAD(P)H and the regulation of the NAD+/NADH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na2EA) causes a decrease in pyruvate and NADH, leading to a decrease in producing ATP via cellular respiration and oxidative phosphorylation. ME2 inhibition also decreases NADPH levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na2EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.

关键词： ME2 silencing Pyruvate metabolism ROS homeostasis Apoptosis Cellular respiration

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