ABSTRACT
To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (ßs = 0.069), ACA (ßs = 0.194), PCA (ßs = 0.187), ACE (ßs = 0.072), PCAP (ßs = 0.087), and ACD (ßs = 0.027) (all P < 0.05), but was negatively correlated to WTW (ßs = - 0.432), CCT (ßs = - 0.087), CV-3 mm (ßs = - 0.066), ACAP (ßs = - 0.043), PCE (ßs = - 0.062), and ACV (ßs = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia.
Subject(s)
Astigmatism , Corneal Diseases , Myopia , Adult , Female , Humans , Anterior Chamber/diagnostic imaging , Anterior Chamber/pathology , Astigmatism/pathology , Biometry , Cornea/pathology , Corneal Diseases/pathology , Myopia/pathology , Retrospective StudiesABSTRACT
The interactions between white-to-white corneal diameter (WTW) and other ocular biometrics are important for planning of refractive surgery and understanding of ocular structural changes in myopia, but such interactions are rarely investigated in young myopic adults. This is a retrospective study involving 7893 young myopic adults from five centers. WTW and other ocular biometrics were measured by Pentacam. The ocular biometrics included anterior corneal curvature (AK) and posterior corneal curvature (PK), central corneal thickness (CCT) and corneal volume (CV), anterior and corneal eccentricity and asphericity, anterior corneal astigmatism (ACA) and posterior corneal astigmatism, anterior chamber depth (ACD), and anterior chamber volume (ACV). The ocular biometrics were compared among eyes of different WTW quartiles. Multivariate linear regression was used to assess the linear associations between WTW and other ocular biometrics adjusting for age, gender and spherical equivalent. In eyes of different WTW quartiles, other ocular biometrics were also significantly different (all P < 0.05). After adjusting for age, gender and spherical equivalent, WTW was positively correlated to AK (ß = 0.26 to 0.29), ACA (ß = 0.13), anterior corneal asphericity (ß = 0.05), PK (ß = 0.33 to 0.34), posterior corneal asphericity (ß = 0.13), ACD (ß = 0.29), and ACV (ß = 40.69), and was negatively correlated to CCT (ß = - 6.83), CV (ß = - 0.06 to - 0.78), anterior corneal eccentricity (ß = - 0.035), and posterior corneal eccentricity (ß = - 0.14) (all P < 0.001). In conclusion, we found that in young myopic adults, larger WTW was associated with thinner corneal thickness, flatter corneal curvature, more anterior corneal toricity, less corneal eccentricity and asphericity, and broader anterior chamber. Our findings may fill in the gap of literature, and help us better understand how the anterior segment structures interact with the WTW in myopia.
Subject(s)
Astigmatism , Myopia , Adult , Humans , Astigmatism/surgery , Retrospective Studies , Myopia/surgery , Cornea , BiometryABSTRACT
BACKGROUND: Metabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood. METHODS: Pregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos. RESULTS: We showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts. CONCLUSIONS: These results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.
ABSTRACT
BACKGROUND: This study aims to identify the relationship between iris -ciliary angle (ICA) and the vault. Additionally, we also seek to investigate the chain mediating effects of the ICL haptic related factors on this relationship. METHODS: The participants were categorized into three groups according to the ICA value as follows: low ICA group (< 35°); moderate ICA group (35°-70°); high ICA group (> 70°). We compared the preoperative ocular characteristics and postoperative examinations among the three groups. Multiple variable stepwise regression was performed to establish the vault prediction formula. The Process V4.0 in SPSS and Hayes's PROCESS model 6 was conducted to further elucidate the mediating effects of the final tip point of ICL haptic and the ICL arc-lens arc on the relationship between the ICA and vault. RESULTS: There was a significant difference in the positions of the ICL haptic among three ICA groups. The regression vault equation was Vault = 679.42-7.26*TCA + 192.30*ACD-196.37*CLR + 73.21* STS(horizontal).A significant negative correlation was found between the ICA and vault (P < 0.01).The chain mediation model revealed that the final tip point of ICL haptic and the ICL arc-Lens arc were sequential mediators between ICA and vault (effect = -1.63, 95% CI = -2.72--0.73). CONCLUSION: The ICA was associated with vault via the mediation effect of the final tip point of the ICL haptic and the ICL arc -lens arc. Assessment of ICL haptic related parameters adds significant information to interpret the vault after surgery.
Subject(s)
Myopia , Phakic Intraocular Lenses , Humans , Visual Acuity , Lens Implantation, Intraocular , Myopia/surgery , Haptic Technology , Iris/surgery , Retrospective StudiesABSTRACT
Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone propagation remains unclear. Here we show that Mcm2-mutated or Pole3-deleted mouse embryonic stem cells (ESCs) display aberrant histone landscapes and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality. ESCs with biased parental histone transfer exhibit increased epigenetic heterogeneity, showing altered histone variant H3.3 and H3K27me3 patterning at genomic sites regulating differentiation genes. Our results indicate that the lagging strand pattern of H3.3 leads to the redistribution of H3K27me3 in Mcm2-2A ESCs. We demonstrate that symmetric parental histone deposition to sister chromatids contributes to cellular differentiation and development.
Subject(s)
Histones , Mouse Embryonic Stem Cells , Animals , Mice , Histones/genetics , Embryonic Stem Cells , Cell Differentiation/genetics , DNA HelicasesABSTRACT
The liver is an essential multifunctional organ, which constantly communicates with nearly all tissues. It has raised the concern that microgravity exposure can lead to liver dysfunction and metabolic syndromes. However, molecular mechanisms and intervention measures of the adverse effects of microgravity on hepatocytes are limited. In this study, we utilized the random positioning machine culture system to investigate the adverse effects on hepatocytes under simulated microgravity (SMG). Our results showed that SMG impaired hepatocyte viability, causing cell cycle arrest and apoptosis. Compared to normal gravity, it also triggered lipid accumulation, elevated triglyceride (TG) and ROS levels, and impaired mitochondria function in hepatocytes. Furthermore, RNA sequencing results showed that SMG upregulated genes implicated in lipid metabolisms, including PPARγ, PLIN2, CD36, FABPs, etc. Importantly, all these defects can be suppressed by melatonin, a potent antioxidant secreted by the pineal gland, suggesting its potential use of therapeutic intervention.
Subject(s)
Melatonin , Weightlessness , Melatonin/pharmacology , Lipid Metabolism , Hepatocytes/metabolism , Mitochondria/metabolism , Lipids/pharmacologyABSTRACT
The wavelength of microwave is longer than that of lightwave, causing the interferometric optical path difference induced by the measurand changes to be relatively smaller than that of microwave, which results in the lower sensitivity of sapphire fiber Fabry-Perot interferometer (FPI) sensor in microwave band. To improve sensitivity, a parallel FPI sensing system is constructed, in which a section of sapphire fiber connected to a single-mode transmission fiber is used as a sensing FPI, and a single-mode fiber (SMF) with a slightly different optical path from a sensing FPI is utilized as a reference FPI. By connecting two FPIs in parallel, Vernier effect is formed to improve sensitivity. The influence of relationship between the optical path difference of the reference FPI and the sensing FPI on the sensitivity amplification factor is analyzed based on the microwave interference spectrum of the parallel FPI. A section of sapphire fiber with the length of 8â cm is used as temperature sensor to construct high-temperature sensing system. The results demonstrate that the temperature sensitivity reaches about 2338.68kHz/°C, which is approximately 130 times higher than that of the sensing FPI alone. Furthermore, when the difference of optical path between the sensing FPI and the reference FPI is kept constant while the sensing FPI is unchanged, the amplification factor of the temperature sensitivity is approximately 2.64 times higher with longer length of the reference FPI compared to the situation with shorter length of the reference FPI.
ABSTRACT
The increasing number of astronauts entering microgravity environments for long-term space missions has resulted in serious health problems, including accidental injury and trauma. Skin, as the largest organ and outermost layer of the human body, has the ability to self-renew and withstand a variety of harmful biological and environmental influences. Recent spaceflight experiments and simulated studies have begun to concern the effects of microgravity on the growth of skin cells and the process of cutaneous wound healing. However, the mechanisms of the adverse effects of microgravity on skin cells and potential intervention measures are still limited. Stem cells and their exosomes provide unique opportunities for the cutaneous wound healing as they have been used to improve skin repair. This review discusses the effects of microgravity on wound healing, from cell morphological changes to molecular level alterations. Furthermore, the current research on wound healing treatment utilizing stem cells and their exosomes on the ground is summarized. Finally, this review proposes promising therapeutic strategies using stem cells or exosomes for wound healing in the microgravity environment. Graphical Abstract.
ABSTRACT
Silicon suboxide (SiOx) anodes have attracted considerable attention owing to their excellent cycling performance and rate capability compared to silicon (Si) anodes. However, SiOx anodes suffer from high volume expansion similar to Si anodes, which has been a challenge in developing suitable commercial binders. In this study, a water-soluble polyamide acid (WS-PAA) binder with ionic bonds was synthesized. The amide bonds inherent in the WS-PAA binder form a stable hydrogen bond with the SiOx anode and provide sufficient mechanical strength for the prepared electrodes. In addition, the ionic bonds introduced by triethylamine (TEA) induce water solubility and new Li+ transport channels to the binder, achieving enhanced electrochemical properties for the resulting SiOx electrodes, such as cycling and rate capability. The SiOx anode with the WS-PAA binder exhibited a high initial capacity of 1004.7 mAh·g-1 at a current density of 0.8 A·g-1 and a capacity retention of 84.9% after 200 cycles. Therefore, WS-PAA is a promising binder for SiOx anodes compared with CMC and SA.
ABSTRACT
Microgravity has been shown to induce many changes in cell growth and differentiation due to offloading the gravitational strain normally exerted on cells. Although many studies have used two-dimensional (2D) cell culture systems to investigate the effects of microgravity on cell growth, three-dimensional (3D) culture scaffolds can offer more direct indications of the modified cell response to microgravity-related dysregulations compared to 2D culture methods. Thus, knowledge of 3D cell culture is essential for better understanding the in vivo tissue function and physiological response under microgravity conditions. This review discusses the advances in 2D and 3D cell culture studies, particularly emphasizing the role of hydrogels, which can provide cells with a mimic in vivo environment to collect a more natural response. We also summarized recent studies about cell growth and differentiation under real microgravity or simulated microgravity conditions using ground-based equipment. Finally, we anticipate that hydrogel-based 3D culture models will play an essential role in constructing organoids, discovering the causes of microgravity-dependent molecular and cellular changes, improving space tissue regeneration, and developing innovative therapeutic strategies. Future research into the 3D culture in microgravity conditions could lead to valuable therapeutic applications in health and pharmaceuticals.
ABSTRACT
BACKGROUND: Acute pancreatitis in pregnancy (APIP) with a high risk of death is extremely harmful to mother and fetus. There are few models specifically designed to assess the severity of APIP. Our study aimed to establish a clinical model for early prediction of severity of APIP. METHODS: A retrospective study in a total of 188 patients with APIP was enrolled. The hematological indicators, IAP (intra-abdominal pressure) and clinical data were obtained for statistical analysis and prediction model construction. RESULTS: According to univariate and multivariate logistic regression analysis, we found that red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR) and Intra-abdominal pressure (IAP) are prediction indexes of the severity in APIP (p-value < 0.05). Our novel clinical prediction model was created by based on the above three risk factors and showed superior predictive power in primary cohort (AUC = 0.895) and validation cohort (AUC = 0.863). A nomogram for severe acute pancreatitis in pregnancy (SAPIP) was created based on the three indicators. The nomogram was well-calibrated. CONCLUSION: RDW, NLR and IAP were the independent risk factors of APIP. Our clinical prediction model of severity in APIP based on RDW, NLR and IAP with predictive evaluation is accurate and effective.
Subject(s)
Pancreatitis , Pregnancy , Female , Humans , Pancreatitis/diagnosis , Pancreatitis/etiology , Neutrophils , Erythrocyte Indices , Retrospective Studies , Acute Disease , Models, Statistical , Prognosis , LymphocytesABSTRACT
Utilizing the periodicity of the rotating machinery, dynamic clearance measurement can be achieved with a single swept light source without any additional auxiliary devices, which has the advantages of simplicity and reliability. However, there is a shortcoming that previous algorithm is not fast enough to achieve real-time measurement when the machinery rotates at high speed. Aiming at this shortcoming, utilizing the correlation between mimic signal and measurement signal, combined with information for multiple periods, the fast algorithms and dynamic clearance corrected model were proposed. And the relationship between demodulation speed and cycle numbers was also discussed. Simulation was carried out to discuss the influence of different algorithm on the demodulation speed and accuracy. A test system was set up in the simulated environment for clearance measurement, and the results show that, the demodulation time of the proposed algorithm costs decreased dramatically, the speed has increased by about ten times, and the dynamic clearance measurement error is less than 2 µm.
ABSTRACT
Transient receptor potential melastatin 8 (TRPM8) play crucial roles in solid tumors such as prostate and breast cancers. But the role of TRPM8 in hepatocellular carcinoma (HCC) and its underlying molecular mechanisms remain largely unknown. In this study, the functional roles of TRPM8 in HCC were systematically investigated for the first time. It was found that the expression level of TRPM8 was significantly upregulated in HCC, which was positively correlated with the worse clinicopathological characteristics. Functional studies revealed that pharmacological inhibition or genetic downregulation of TRPM8 ameliorated hepatocarcinogenesis in vitro and in vivo. Mechanistically, the oncogenic role of TRPM8 in HCC was at least partially achieved by affecting mitochondrial function. TRPM8 could modulate the expression of nucleolar relative molecule-small nucleolar RNA, H/ACA box 55 (SNORA55) by inducing transformation of chromatin structure and histone modification type. These data suggest that as a bridge molecule in TRPM8-triggered HCC, SNORA55 can migrate from nucleus to mitochondria and exert oncogenic role by affecting mitochondria function through targeting ATP5A1 and ATP5B. Herein, we uncovered the potent oncogenic role of TRPM8 in HCC by inducing nuclear and mitochondrial dysfunction in a SNORA55 dependent manner, and provided a potential therapeutic target for HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , TRPM Cation Channels , Male , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , RNA, Small Nucleolar/metabolism , Prostate/pathology , Mitochondria/genetics , Mitochondria/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism , Membrane Proteins/geneticsABSTRACT
Ovarian follicles are the fundamental structures that support oocyte development, and communications between oocytes and follicle somatic cells are crucial for oogenesis. However, it is unknown that whether exposure to microgravity influences cellular communications and ovarian follicle development, which might be harmful for female fertility. By 3D culturing of ovarian follicles under simulated microgravity (SMG) conditions in a rotating cell culture system, we found that SMG treatment did not affect the survival or general growth of follicles but decreased the quality of cultured follicles released oocytes. Ultrastructure detections by high-resolution imaging showed that the development of cellular communicating structures, including granulosa cell transzonal projections and oocyte microvilli, were markedly disrupted. These abnormalities caused chaotic polarity of granulosa cells (GCs) and a decrease in oocyte-secreted factors, such as Growth Differentiation Factor 9 (GDF9), which led to decreased quality of oocytes in these follicles. Therefore, the quality of oocytes was dramatically improved by the supplementations of GDF9 and NADPH-oxidase inhibitor apocynin. Together, our results suggest that exposure to simulated microgravity impairs the ultrastructure of ovarian follicles. Such impairment may affect female fertility in space environment.
ABSTRACT
PURPOSE: To assess the position of implantable collamer lens (ICL) haptic after ICL V4C implantation using standardized panoramic ultrasound bimicroscopy (UBM), to analyze its characteristics, associated factors, and the relationship with the clinical vault quantitatively. SETTING: Hankou Aier Eye Hospital, Wuhan, Hubei, China. DESIGN: Cross-sectional study. METHODS: 167 subjects (323 eyes) implanted with ICL V4C who had a 3-month follow-up with UBM examination were included in this study. The relative position of ICL to the adjacent structure and ICL haptic-related parameters (the final tip point of ICL haptic [ftICL haptic], measured from the scleral spur to the final tip of the ICL haptic, the posterior of the ICL to ICL haptic [ICL arc], measured from the posterior surface of the ICL to the ICL haptic plane, and the height of the crystalline lens from the ICL haptic (lens arc), measured from the anterior surface of the crystalline lens to the ICL haptic plane and other parameters), were estimated on the UBM image. Eyes were divided into 3 subgroups according to the ftICL haptic (Group 1: ≤0.5 mm; Group 2: 0.5 to 1.0 mm; and Group 3:≥1.0 mm, respectively), and the factors associated with the ICL haptic-related parameters and their impact on the clinical vault were evaluated. RESULTS: The haptics could be imaged in the ciliary sulcus, on the ciliary body, and under the ciliary body in 629 (48.7%), 525 (40.6%), and 138 (10.7%) eyes, respectively. The ftICL haptic and the summation of ICL arc and lens arc showed a correlation with the clinical vault ( r = -0.34, P = .00; r = 0.87, P = .00). When the ftICL haptic results were divided into 3 groups, the percentage of eyes that exhibited clinical vault >750 µm were lowest in Group 3. Multivariate regression analysis showed spherical equivalent, white-to-white (WTW), anterior chamber volume (ACV) and iris-ciliary angle (ICA); the difference between the implanted ICL size and horizontal sulcus-to-sulcus (ICL size-STS) were associated with the ftICL haptic. The IOP, WTW, ACV, and the ICL size-STS were significantly associated with ICL arc, while the ICA and lens rise were associated with lens arc. CONCLUSIONS: The position of ICL haptic was associated with the clinical vault. Its quantitative evaluation may provide valuable information to help clinicians to select the best ICL size before surgery and understand the formation of clinical vault after surgery.
Subject(s)
Myopia , Phakic Intraocular Lenses , Humans , Visual Acuity , Lens Implantation, Intraocular/methods , Cross-Sectional Studies , Haptic Technology , Myopia/surgery , Ciliary Body , Retrospective StudiesABSTRACT
G protein-coupled receptor 158 (GPR158) is a member of class C G protein-coupled receptors (GPCRs) and is highly expressed in the central nervous system (CNS) while lowly expressed in peripheral tissues. Previous studies have mainly focused on its functions in the CNS, such as regulating emotions, memory, and cognitive functions, whereas studies on its role in the non-nervous system are limited. It has been recently reported that GPR158 is directly involved in adrenal regulation, suggesting its role in peripheral tissues. Moreover, GPR158 is a stable dimer coupled to the regulator of G protein signaling protein 7 (RGS7) that forms the GPR158-RGS7-Gß5 complex. Given that the RGS7-Gß5 complex is implicated in endocrine functions, we speculate that GPR158 might be an active component of the endocrine system. Herein, we reviewed the relevant literature on GPR158, including its molecular structure, regulatory molecules, expression, and functions, and highlighted its roles in endocrine regulation. These findings not only enhance our understanding of GPR158 from an endocrine perspective but also provide valuable insights into drug exploration targeting GPR158 and their applicability in endocrine disorders.
ABSTRACT
Cranial radiation therapy is one of the most effective treatments for childhood brain cancers. Despite the ameliorated survival rate of juvenile patients, radiation exposure-induced brain neurogenic region injury could markedly impair patients' cognitive functions and even their quality of life. Determining the mechanism underlying neural stem cells (NSCs) response to irradiation stress is a crucial therapeutic strategy for cognitive impairment. The present study demonstrated that X-ray irradiation arrested NSCs' cell cycle and impacted cell differentiation. To further characterize irradiation-induced molecular alterations in NSCs, two-dimensional high-resolution mass spectrometry-based quantitative proteomics analyses were conducted to explore the mechanism underlying ionizing radiation's influence on stem cell differentiation. We observed that ionizing radiation suppressed intracellular protein transport, neuron projection development, etc., particularly in differentiated cells. Redox proteomics was performed for the quantification of cysteine thiol modifications in order to profile the oxidation-reduction status of proteins in stem cells that underwent ionizing radiation treatment. Via conjoint screening of protein expression abundance and redox status datasets, several significantly expressed and oxidized proteins were identified in differentiating NSCs subjected to X-ray irradiation. Among these proteins, succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (sdha) and the acyl carrier protein, mitochondrial (Ndufab1) were highly related to neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Huntington's disease, illustrating the dual-character of NSCs in cell differentiation: following exposure to ionizing radiation, the normal differentiation of NSCs was compromised, and the upregulated oxidized proteins implied a degenerative differentiation trajectory. These findings could be integrated into research on neurodegenerative diseases and future preventive strategies.
Subject(s)
Brain Injuries , Neural Stem Cells , Humans , Child , Proteomics , Quality of Life , Neural Stem Cells/metabolism , Cell Differentiation , Radiation, Ionizing , Brain Injuries/metabolismABSTRACT
Impairment of liver regeneration leads to severe morbidity in acute and chronic severe liver disease. Transient receptor potential melastain 8 (TRPM8) is involved in a variety of processes, including temperature sensing, ion homeostasis, and cell proliferation. However, whether TRPM8 contributes to liver regeneration is still unclear. We assessed the effect and mechanism of TRPM8 in liver regeneration and hepatocyte proliferation in vivo and in vitro. In this study, we found that TRPM8 deficiency impairs liver regeneration in mice. Mechanistically, the results revealed that mitochondrial energy metabolism was attenuated in livers from TRPM8 knockout (KO) mice. Furthermore, we found that TRPM8 contributes to the proliferation of hepatocytes via PGC1α. Taken together, this study shows that TRPM8 contributes to liver regeneration in mice after hepatectomy. Genetic approaches and pharmacological approaches to regulate TRPM8 activity may be beneficial to the promotion of liver regeneration.
Subject(s)
Liver Regeneration , TRPM Cation Channels , Mice , Animals , Liver Regeneration/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Hepatocytes/metabolism , Hepatectomy , Liver/metabolism , Cell Proliferation , Mice, Knockout , Energy Metabolism , Mice, Inbred C57BL , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolismABSTRACT
Synthetic hydrogels from polyisocyanides (PIC) are a type of novel thermoreversible biomaterials, which can covalently bind biomolecules such as adhesion peptides to provide a suitable extracellular matrix (ECM)-like microenvironment for different cells. Although we have demonstrated that PIC is suitable for three-dimensional (3D) culture of several cell types, it is unknown whether this hydrogel sustains the proliferation and passaging of cells originating from different germ layers. In the present study, we propose a 3D culture system for three representative cell sources: Schwann cells (ectoderm), hepatocytes (endoderm), and endothelial cells (mesoderm). Both Schwann cells and hepatocytes proliferated into multicellular spheroids and maintained their properties, regardless of the amount of cell-adhesive RGD motifs in long-term culture. Notably, Schwann cells grew into larger spheroids in RGD-free PIC than in PIC-RGD, while HL-7702 showed the opposite behavior. Endothelial cells (human umbilical vein endothelial cells, HUVECs) spread and formed an endothelial cell (EC) network only in PIC-RGD. Moreover, in a hepatocyte/HUVEC co-culture system, the characteristics of both cells were well kept for a long period in PIC-RGD. In all, our work highlights a simple ECM mimic that supports the growth and phenotype maintenance of cells from all germ layers in the long term. Our findings might contribute to research on biological development, organoid engineering, and in vitro drug screening.