ABSTRACT
Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through in vitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.
ABSTRACT
Bioactive metal-based nanostructures, particularly zinc oxide (ZnO), are promising materials for bone tissue engineering. However, integrating them into 3D-printed polymers using traditional blending methods reduces the cell performance. Alternative surface deposition techniques often require extreme conditions that are unsuitable for polymers. To address these issues, we propose a metal-assisted hydrothermal synthesis method to modify 3D printed polycaprolactone (PCL) scaffolds with ZnO nanoparticles (NPs), facilitating the growth of ZnO nanoarrays (NAs) at a low-temperature (55 °C). Physicochemical characterizations revealed that the ZnO NPs form both physical and chemical bonds with the PCL surface; chemical bonding occurs between the carboxylate groups of PCL and Zn(OH)2 during seed deposition and hydrothermal synthesis. The ZnO NPs and NAs grown for a longer time (18 h) on the surface of PCL scaffolds exhibit significant proliferation and early differentiation of osteoblast-like cells. The proposed method is suitable for the surface modification of thermally degradable polymers, opening up new possibilities for the deposition of diverse metals.
ABSTRACT
Wound dressings made from natural-derived polymers are highly valued for their biocompatibility, biodegradability, and biofunctionality. However, natural polymer-based hydrogels can come with their own set of limitations, such as low mechanical strength, limited cell affinity, and the potential cytotoxicity of cross-linkers, which delineate the boundaries of their usage and hamper their practical application. To overcome the limitation of natural-derived polymers, this study utilized a mixture of oxidized alginate and gelatin with 5 mg/mL polycaprolactone (PCL):gelatin nanofiber fragments at a ratio of 7:3 (OGN-7) to develop a hydrogel composite wound dressing that can be injected and has the ability to be remended. The in situ formation of the remendable hydrogel is facilitated by dual cross-linking of oxidized alginate chains with gelatin and PCL/gelatin nanofibers through Schiff-base mechanisms, supported by the physical integration of nanofibers, thereby obviating the need for additional cross-linking agents. Furthermore, OGN-7 exhibits increased stiffness (γ = 79.4-316.3%), reduced gelation time (543 ± 5 to 475 ± 5 s), improved remendability of the hydrogel, and excellent biocompatibility. Notably, OGN-7 achieves full fusion within 1 h of incubation and maintains structural integrity under external stress, effectively overcoming the inherent mechanical weaknesses of natural polymer-based dressings and enhancing biofunctionality. The therapeutic efficacy of OGN-7 was validated through a full-thickness in vivo wound healing analysis, which demonstrated that OGN-7 significantly accelerates wound closure compared to alginate-based dressings and control groups. Histological analysis further revealed that re-epithelialization and collagen deposition were markedly enhanced in the regenerating skin of the OGN-7 group, confirming the superior therapeutic performance of OGN-7. In summary, OGN-7 optimized the synergistic effects of natural polymers, which enhances their collective functionality as a wound dressing and expands their utility across diverse biomedical applications.
Subject(s)
Alginates , Gelatin , Hydrogels , Nanofibers , Wound Healing , Alginates/chemistry , Gelatin/chemistry , Nanofibers/chemistry , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Mice , Bandages , Cross-Linking Reagents/chemistry , Polyesters/chemistry , Regeneration/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , MaleABSTRACT
Rheumatoid arthritis (RA) is known to be caused by autoimmune disorders and can be partially alleviated through Disease-Modifying Antirheumatic Drugs (DMARDs) therapy. However, due to significant variations in the physical environment and condition of each RA patient, the types and doses of DMARDs prescribed can differ greatly. Consequently, there is a need for a platform based on patient-derived cells to determine the effectiveness of specific DMARDs for individual patient. In this study, we established an RA three-dimensional (3D) spheroid that mimics the human body's 3D environment, enabling high-throughput assays by culturing patient-derived synovial cells on a macroscale-patterned polycaprolactone (PCL) scaffold. Fibroblast-like synoviocytes (FLSs) from patient and human umbilical vein endothelial cells (HUVECs) were co-cultured to simulate vascular delivery. Additionally, RA characteristics were identified at both the genetic and cytokine levels using real-time polymerase chain reaction (RT-qPCR) and dot blot assay. The similarities in junctions and adhesion were demonstrated in both actual RA patient tissues and 3D spheroids. The 3D RA spheroid was treated with representative DMARDs, observing changes in reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) levels, and inflammatory cytokine responses to confirm the varying cell reactions depending on the DMARDs used. This study underscores the significance of the 3D drug screening platform, which can be applied to diverse inflammatory disease treatments as a personalized drug screening system. We anticipate that this platform will become an indispensable tool for advancing and developing personalized DMARD treatment strategies.
ABSTRACT
This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.
Subject(s)
Lung Neoplasms , Metal Nanoparticles , Humans , X-Rays , Gold/pharmacology , Computer Simulation , Monte Carlo MethodABSTRACT
Gelatin methacrylate (GelMA) bioink has been widely used in bioprinting because it is a printable and biocompatible biomaterial. However, it is difficult to print GelMA bioink without any temperature control because it has a thermally-sensitive rheological property. Therefore, in this study, we developed a temperature-controlled printing system in real time without affecting the viability of the cells encapsulated in the bioink. In addition, a skin-derived decellularized extracellular matrix (SdECM) was printed with GelMA to better mimic the native tissue environment compared with solely using GelMA bioink with the enhancement of structural stability. The temperature setting accuracy was calculated to be 98.58 ± 1.8 % for the module and 99.48 ± 1.33 % for the plate from 5 °C to 37 °C. The group of the temperature of the module at 10 °C and the plate at 20 °C have 93.84 % cell viability with the printable range in the printability window. In particular, the cell viability and proliferation were increased in the encapsulated fibroblasts in the GelMA/SdECM bioink, relative to the GelMA bioink, with a morphology that significantly spread for seven days. The gene expression and growth factors related to skin tissue regeneration were relatively upregulated with SdECM components. In the bioprinting process, the rheological properties of the GelMA/SdECM bioink were successfully adjusted in real time to increase printability, and the native skin tissue mimicked components providing tissue-specific biofunctions to the encapsulated cells. The developed bioprinting strategies and bioinks could support future studies related to the skin tissue reconstruction, regeneration, and other medical applications using the bioprinting process.
Subject(s)
Gelatin , Tissue Scaffolds , Tissue Scaffolds/chemistry , Gelatin/chemistry , Methacrylates/chemistry , Printing, Three-Dimensional , Biocompatible Materials , Tissue EngineeringABSTRACT
Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.
Subject(s)
Skin, Artificial , Humans , Bionics , Touch/physiology , Skin , Wound Healing , Sense OrgansABSTRACT
Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.
Subject(s)
Ferroptosis , Nanoparticles , Ferroptosis/drug effects , Humans , Nanoparticles/chemistry , Animals , X-Rays , Cell Line, Tumor , Mice , Apoptosis/drug effects , Hyaluronic Acid/chemistry , Combined Modality TherapyABSTRACT
Retinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration. The injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitors, was loaded into the hydrogel to attenuate inflammatory factors. On-demand anti-inflammatory effects of microglia cells via the drug-loaded IRH were verified in vitro and in vivo retinal degeneration 10 (rd10) mice model. Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest the IRH reported here can be used to considerably delay vision loss caused by RP.
ABSTRACT
Extrusion-based bioprinting technology is widely used for tissue regeneration and reconstruction. However, the method that uses only hydrogel as the bioink base material exhibits limited biofunctional properties and needs improvement to achieve the desired tissue regeneration. In this study, we present a three-dimensionally printed bioactive microparticle-loaded scaffold for use in bone regeneration applications. The unique structure of the microparticles provided sustained release of growth factor for > 4 weeks without the use of toxic or harmful substances. Before and after printing, the optimal particle ratio in the bioink for cell viability demonstrated a survival rate of ≥ 85% over 7 days. Notably, osteogenic differentiation and mineralization-mediated by human periosteum-derived cells in scaffolds with bioactive microparticles-increased over a 2-week interval. Here, we present an alternative bioprinting strategy that uses the sustained release of bioactive microparticles to improve biofunctional properties in a manner that is acceptable for clinical bone regeneration applications.
ABSTRACT
BACKGROUND: Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results. METHOD: To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels. RESULTS: It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model. CONCLUSION: We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.
ABSTRACT
Wound dressings have been designed to provide the optimal environment to fibroblasts, keratinocytes, and macrophages to promote wound healing while inhibiting potential microbial infection. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel with a gelatin backbone that contains natural cell binding motifs such as arginine-glycine-aspartic acid (RGD) and MMP-sensitive degradation sites, making it an ideal material for wound dressing. However, GelMA alone is unable to stably protect the wound and regulate cellular activities due to its weak mechanical properties and nonmicropatterned surface, limiting its application as a wound dressing. Herein, we report the development of a hydrogel-nanofiber composite wound dressing utilizing GelMA and poly(caprolactone) (PCL)/gelatin nanofiber, which can systematically manage the skin regeneration process with an enhanced mechanical property and micropatterned surface. GelMA sandwiched between electrospun aligned and interlaced nanofibers that mimic epidermis and dermis layers, respectively, increased the stiffness of the resulting hydrogel composite with a comparable swelling rate as GelMA. Fabricated hydrogel composite was determined to be biocompatible and nontoxic. In addition to the beneficial effect of GelMA in accelerating wound healing, subsequent histological analysis revealed upregulated re-epithelialization of granulation tissue and deposition of mature collagen. Hydrogel composite interacted with fibroblasts to regulate their morphology, proliferation, and collagen synthesis, as well as the expression of α-SMA, TGF-ß, and collagen I and III during the wound healing process both in vitro and in vivo. Taken together, we propose hydrogel/nanofiber composite as a wound dressing of the next generation that can induce skin tissue layer regeneration beyond the basic wound closure promotion of present dressings.
Subject(s)
Hydrogels , Nanofibers , Hydrogels/chemistry , Gelatin/pharmacology , Gelatin/chemistry , Nanofibers/therapeutic use , Nanofibers/chemistry , Mechanotransduction, Cellular , Wound Healing , Collagen/pharmacology , BandagesABSTRACT
Bioresorbable implantable medical devices can be employed in versatile clinical scenarios that burden patients with complications and surgical removal of conventional devices. However, a shortage of suitable electricalinterconnection materials limits the development of bioresorbable electronic systems. Therefore, this study highlights a highly conductive, naturally resorbable paste exhibiting enhanced electrical conductivity and mechanical stability that can solve the existing problems of bioresorbable interconnections. Multifaceted experiments on electrical and physical properties were used to optimize the composition of pastes containing beeswax, submicron tungstenparticles, and glycofurol. These pastes embody isotropic conductive paths for three-dimensional interconnects and function as antennas, sensors, and contact pads for bioresorbable electronic devices. The degradation behavior in aqueous solutions was used to assess its stability and ability to retain electrical conductance (â¼7 âkS/m) and structural form over the requisite dissolution period. In vitro and in vivo biocompatibility tests clarified the safety of the paste as an implantable material.
ABSTRACT
Ferroptosis, a cell death pathway that is induced in response to iron, has recently attracted remarkable attention given its emerging therapeutic potential in cancer cells. The need for a promising modality to improve chemotherapy's efficacy through this pathway has been urgent in recent years, and this non-apoptotic cell death pathway accumulates reactive oxygen species (ROS) and is subsequently involved in lipid peroxidation. Here, we report cancer-targeting nanoparticles that possess highly efficient cancer-targeting ability and minimal systemic toxicity, thereby leading to ferroptosis. To overcome the limit of actual clinical application, which is the ultimate goal due to safety issues, we designed safe nanoparticles that can be applied clinically. Nanoparticles containing ferroptosis-dependent iron and FDA-approved hyaluronic acid (FHA NPs) are fabricated by controlling physicochemical properties, and the FHA NPs specifically induce ROS production and lipid peroxidation in cancer cells without affecting normal cells. The excellent in vivo anti-tumor therapeutic effect of FHA NPs was confirmed in the A549 tumor-bearing mice model, indicating that the induction of FHA NP-mediated cell death via the ferroptosis pathway could serve as a powerful platform in anticancer therapy. We believe that this newly proposed FHA NP-induced ferroptosis strategy is a promising system that offers the potential for efficient cancer treatment and provides insight into the safe design of nanomedicines for clinical applications.
ABSTRACT
Accumulating evidence has shown that sirtuin 7 (SIRT7), a mediator of various cellular activities, plays an important role in the pathogenesis of various immune-mediated inflammatory disorders. However, information remains limited regarding the role of SIRT7 in intestinal inflammation. We used a murine colitis model to investigate the role of SIRT7 in intestinal immunity and whether SIRT7 inhibitors could attenuate the intestinal inflammatory response. Mice were divided into three groups: control, colitis-induced, and SIRT7-inhibitor-treated. A colitis mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin, as in our previous study. Quantitative analyses of inflammatory cytokines and SIRT7 levels in the colonic mucosa were performed to compare the changes in inflammatory responses between the three groups. The colitis group showed increased levels of inflammatory cytokines and SIRT7 in the colonic mucosa. The inflammatory reaction was suppressed in colitis-induced mice administered the SIRT7 inhibitor. The qRT-PCR results showed normalization of inflammatory cytokines in the SIRT7 inhibitor-treated group. Histologic study revealed a decrease in the extent of inflammation after SIRT7 treatment. We also observed that the degree of clinical inflammation was improved in SIRT7-treated mice. Our study demonstrated that SIRT7 inhibition attenuated the inflammatory response in the colon of mice, suggesting a possible role for SIRT7 in the pathogenesis of immune-mediated intestinal inflammation.
ABSTRACT
Many studies have recently produced artificial enzymes with metal nanoparticles (NPs) to overcome the limitations of natural enzymes, such as low stability, high cost, and storage problems. In particular, gold NPs exhibit peroxidase-like activity and are strongly influenced by external parameters, such as pH, temperature, size, shape, and functional layer, which change the enzyme activity. Here, chitosan-capped multibranched Au-Ag-Pt NPs (CCNPs) that mimic peroxidase were synthesized using various peroxidase-mimicking strategies. The results demonstrated that enzyme activity sequentially increased because of the multibranched Au-Ag NPs coated with Pt and chitosan. The enzyme activity of the particle was evaluated through the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), which causes a color change into blue. This change was observable with the naked eye and could be used practically. The color change depended on the concentration of hydrogen peroxide (H2O2), and it was shown that the CCNPs could be applied to measure H2O2 with a limit of detection (LOD) of 0.054 mM. Furthermore, with glucose oxidase, the CCNPs can be used for glucose detection with an LOD of 0.289 mM. Also, the potential of the CCNP application in human serum was shown through the serum test. Thus, this study suggested the utilization of the multibranched Au-Ag-Pt NPs that mimic the peroxidase activity of natural enzymes and the possibility of application in various biological analyses.
ABSTRACT
Tumour-associated macrophages (TAMs) are involved in cancer progression and drug resistance in the tumour microenvironment (TME). Consequently, macrophages as therapeutic targets have garnered increased attention; however, there are hurdles to screening interactions between cancer and macrophages owing to technical difficulties in recapitulatingin vitrophysiological systems. In this study, we propose a simple strategy to construct tumour spheroids with induced M2 macrophage polarization for anticancer drug screening. We observed that cytokine expression related to the TME in three-dimensional (3D) cancer spheroids was enhanced compared with that in two-dimensional conventional cancer cell cultures. We also demonstrated that the 3D breast tumour spheroids promote M2-like TAM polarization via granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor. Furthermore, adipose tissue-derived stem cells, an abundant stromal cell population in the breast cancer TME, further enhanced the M2 phenotype in thein vitrotumour spheroids. Therefore, we propose the tumour spheroids as a drug screening platform to evaluate drug efficacy in cancers. Overall, the simple strategy to form tumour spheroids developed in this study will broaden the understanding of communication between cancer cells and macrophages and contribute to the evaluation of cancers and the development of better strategies for their therapy and management.
Subject(s)
Antineoplastic Agents , Granulocyte-Macrophage Colony-Stimulating Factor , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cytokines/metabolism , Drug Evaluation, Preclinical , Granulocyte Colony-Stimulating Factor/metabolism , Macrophages/metabolismABSTRACT
PURPOSE: In women, menopause manifests with a variety of symptoms related to sex-hormone deficiency. Supplementing steroid hormones with pharmacological drugs has been widely practiced. However, considering the possible complications associated with artificial hormone therapy, studies have been conducted to find an alternative to pharmacological hormone replacement therapy. Accordingly, this study aimed to evaluate the efficacy of tissue-based hormone replacement therapy (tHRT) for treating post-menopausal signs and symptoms. MATERIALS AND METHODS: CD-1 mice were ovariectomized, and the ovaries were cryopreserved. Following artificial induction of post-menopausal osteoporosis, cryopreserved ovaries were subcutaneously autografted, and indexes related to bone health were monitored for 12 weeks. Bone mineral density (BMD), bone mineral contents (BMC), total bone volume (BV), and body fat mass were measured by dual energy X-ray absorptiometry. Uterine atrophy was assessed histologically, and bone microstructures were imaged by micro-computed tomography analysis. RESULTS: Regardless of the number of grafted ovaries, the BMC, BMD, and BV values of mice that underwent ovary transplantation were better than those that did not undergo transplantation. The uteruses in these mice were thicker and heavier after auto-transplantation. Furthermore, the bone microstructure recovered after tHRT. CONCLUSION: Recovery of menopause-related bone loss and uterine atrophy was achieved through tHRT. Ovarian tissue cryopreservation and transplantation may be applicable not only in patients wanting to preserve fertility but also in sex hormone-deficient post-menopausal women.
Subject(s)
Hormone Replacement Therapy , Menopause , Absorptiometry, Photon , Animals , Atrophy , Bone Density , Estrogen Replacement Therapy , Female , Hormones , Humans , Mice , X-Ray MicrotomographyABSTRACT
There is an increasing need for fast and accurate assessment of various health conditions, where polydiacetylenes (PDA), having unique stress-sensitive optical properties, have great potential. When the conjugated backbone of PDA is disturbed by steric repulsion between the receptor-target complexes formed at the PDA surface via specific recognition events, the bandgap of PDA increases and produces color change and fluorescent emission as a dual sensory signal. However, this detection mechanism suggests an intrinsic sensitivity limit of PDA platform because unless adjacent receptors are occupied by target molecules no signal is anticipated. A novel approach to improve the sensitivity and limit of detection of PDA sensors has been developed by preoccupying the surface of PDA liposomes with an optimized amount of artificial target molecules named as dummy molecules. The sensitivity and limit of detection (LOD) showed large improvement by the surface-bound dummy molecules. In addition, the dummy strategy was synergically integrated with another sensitivity enhancing method with a different working mechanism in a PDA sensor for Neomycin detection. When optimized, the LOD of the PDA sensor was improved to 7 nM from 80 nM of the control and the signal intensity increased consistently throughout the entire tested concentration range of the target Neomycin. Finally, the general applicability of the dummy strategy to other target molecules was successfully confirmed by implementing the dummy strategy in a PDA sensor for Surfactin detection.
ABSTRACT
Evaluation of position sense post-stroke is essential for rehabilitation. Position sense may be an output of a process needing position information, external torque, and the sense of effort. Even for healthy individuals, it is unclear whether external torque affects position sense. Thus, evaluation of position sense under different external torques in clinical settings is strongly needed. However, simple devices for measuring position sense under different external torques in clinical settings are lacking. Technologically advanced devices that may evaluate the elbow position sense under different torques were reported to be infeasible clinically because of device complexity and the need for technical experts when analyzing data. To address the unmet need, in this study, a simple and light elbow position sense measurement device was developed that allows clinicians to measure elbow position sense under different external torques in the form of position matching error objectively without any technical difficulties. The feasibility of the device, including intra-session intra-rater reliability and test-retest reliability over two consecutive days, was verified to be clinically applicable using tests with 25 healthy subjects. Thanks to its ease of use, high reliability, and ease of data analysis, it is expected that the device can help to evaluate the position sense post-stroke comprehensively.