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BackgroundAlthough previous studies have investigated trends in unmet health care and dental care needs, most have focused on specific groups, such as patients with chronic conditions and older adults, and have been limited by smaller data sets. ObjectiveThis study aims to investigate the trends and relative risk factors for unmet health care and dental care needs, as well as the impact of the COVID-19 pandemic on these needs. MethodsWe assessed unmet health care and dental care needs from 2009 to 2022 using data from the Korea Community Health Survey (KCHS). Our analysis included responses from 2,750,212 individuals. Unmet health care or dental care needs were defined as instances of not receiving medical or dental services deemed necessary by experts or desired by patients. ResultsFrom 2009 to 2022, the study included 2,700,705 individuals (1,229,671 men, 45.53%; 673,780, 24.95%, aged 19-39 years). Unmet health care needs decreased before the COVID-19 pandemic; however, during the pandemic, there was a noticeable increase (βdiff 0.10, 95% CI 0.09-0.11). Unmet dental care needs declined before the pandemic and continued to decrease during the pandemic (βdiff 0.23, 95% CI 0.22-0.24). Overall, the prevalence of unmet dental care needs was significantly higher than that for unmet health care needs. While the prevalence of unmet health care needs generally decreased over time, the β difference during the pandemic increased compared with prepandemic values. ConclusionsOur study is the first to analyze national unmet health care and dental care needs in South Korea using nationally representative, long-term, and large-scale data from the KCHS. We found that while unmet health care needs decreased during COVID-19, the decline was slower compared with previous periods. This suggests a need for more targeted interventions to prevent unmet health care and dental care needs.

Abstract Several functions of autophagy associated with proliferation, differentiation, and migration of endothelial cells have been reported. Due to lack of models recapitulating angiogenic sprouting, functional heterogeneity of autophagy in endothelial cells along angiogenic sprouts remains elusive. Here, we apply an angiogenesis-on-a-chip to reconstruct 3D sprouts with clear endpoints. We perform single-cell RNA sequencing of sprouting endothelial cells from our chip to reveal high activation of autophagy in two endothelial cell populations- proliferating endothelial cells in sprout basements and stalk-like endothelial cells near sprout endpoints- and further the reciprocal expression pattern of autophagy-related genes between stalk- and tip-like endothelial cells near sprout endpoints, implying an association of autophagy with tip-stalk cell specification. Our results suggest a model describing spatially differential roles of autophagy: quality control of proliferating endothelial cells in sprout basements for sprout elongation and tip-stalk cell specification near sprout endpoints, which may change strategies for developing autophagy-based anti-angiogenic therapeutics.

Abstract When producing clothing using virtual fitting technology or purchasing textile and clothing products online, it is challenging to make judgments or communicate information about sensory characteristics, such as drapability and tactile sensations, as there are no clear objective indicators for these factors. Therefore, the study aims to develop a classification system for the sensory properties of fabrics using drapability and tactile characteristics as quantitative indicators. The developed system was verified through subjective evaluations by an expert group, and it was found to be meaningful in reflecting classification levels in practice. The drapability and tactile sensation (softness; TS7) of the fabric were classified using fuzzy c-means cluster analysis, and the results were confirmed through a subjective evaluation by experts. The classification system was then used to predict the classification group, constituted by drapability and tactile characteristics, from mechanical properties using an artificial neural network. The network was trained on 534 fabric samples for drapability and tactile sensation (softness), and it correctly predicted 202 samples out of 243 validation data, with a forecasting accuracy of 83.5%. The developed classification system enables predictions and judgments about subjective characteristics like fabric drapability and tactile sensation based on the mechanical property values of various samples.

Caseous lymphadenitis (CLA) is a chronic and subclinical bacterial disease of ruminants caused by Corynebacterium pseudotuberculosis (C. pseudotuberculosis) infection. Until 2014, there were no reports of CLA outbreaks in South Korea; however, the prevalence of CLA cases has steadily increased. In this study, we used recently obtained field isolates to develop the first inactivated CLA vaccine in South Korea and evaluated it in various animal models. The inactivated vaccine was evaluated for virulence and effectiveness. Mice were tested for virulence and immunization challenges, and guinea pigs and Korean Native Black Goats (KNBGs) evaluated various vaccine concentrations to determine the optimal dose and effectiveness. In the case of KNBGs, clinical symptoms were not observed after vaccination. In addition, CLA-specific IgG was detected at a significantly (p < 0.05) high level and was maintained. In histopathological evaluations, inflammation was predominantly observed in the prefemoral lymph nodes in the non-vaccinated+CHAL group. The genetic diversity of C. pseudotuberculosis, which has become widespread in South Korea, is less than 0.5% our vaccine is expected to prevent infection by a wide range of strains effectively. In summary, our CLA vaccine can potentially prevent CLA and foster the growth of South Korea’s domestic KNBG industry.

Abstract Branchio-oto-renal (BOR)/branchio-otic (BO) syndrome is a rare disorder and exhibits clinically heterogenous phenotypes, marked by abnormalities in the ear, branchial arch, and renal system. Sporadic cases of atypical BOR/BO syndrome have been recently reported; however, evidence on genotype–phenotype correlations and molecular mechanisms of those cases is lacking. We herein identified five SIX1 heterozygous variants (c.307dupC:p.Leu103Profs*51, c.373G>A:p.Glu125Lys, c.386_391del:p.Tyr129_Cys130del, c.397_399del:p.Glu133del, and c.501G>C:p.Gln167His), including three novel variants, through whole-exome sequencing in five unrelated Korean families. All eight affected individuals with SIX1 variants displayed non-syndromic hearing loss (DFNA23) or atypical BO syndrome. The prevalence of major and minor criteria for BOR/BO syndrome was significantly reduced among individuals with SIX1 variants, compared to 15 BOR/BO syndrome families with EYA1 variants. All SIX1 variants interacted with the EYA1 wild-type; their complexes were localized in the nucleus except for the p.Leu103Profs*51 variant. All mutants also showed obvious but varying degrees of reduction in DNA binding affinity, leading to a significant decrease in transcriptional activity. This study presents the first report of SIX1 variants in South Korea, expanding the genotypic and phenotypic spectrum of SIX1 variants, characterized by DFNA23 or atypical BO syndrome, and refines the diverse molecular aspects of SIX1 variants according to the EYA1–SIX1–DNA complex theory.

With the increasing utilization of data in various industries and applications, constructing an efficient data pipeline has become crucial. In this study, we propose a machine learning operations-centric data pipeline specifically designed for an energy consumption management system. This pipeline seamlessly integrates the machine learning model with real-time data management and prediction capabilities. The overall architecture of our proposed pipeline comprises several key components, including Kafka, InfluxDB, Telegraf, Zookeeper, and Grafana. To enable accurate energy consumption predictions, we adopt two time-series prediction models, long short-term memory (LSTM), and seasonal autoregressive integrated moving average (SARIMA). Our analysis reveals a clear trade-off between speed and accuracy, where SARIMA exhibits faster model learning time while LSTM outperforms SARIMA in prediction accuracy. To validate the effectiveness of our pipeline, we measure the overall processing time by optimizing the configuration of Telegraf, which directly impacts the load in the pipeline. The results are promising, as our pipeline achieves an average end-to-end processing time of only 0.39 s for handling 10,000 data records and an impressive 1.26 s when scaling up to 100,000 records. This indicates 30.69–90.88 times faster processing compared to the existing Python-based approach. Additionally, when the number of records increases by ten times, the increased overhead is reduced by 3.07 times. This verifies that the proposed pipeline exhibits an efficient and scalable structure suitable for real-time environments.

In the present study, we prepared an ethanol extract from the flowers of Styphnolobium japonicum L. (SJFE) and found that it contains rutin as a major constituent as well as quercetin kaempferol and isorhamnetin as minor components. In lipopolysaccharide-stimulated RAW 264.7 macrophages, we observed that SJFE significantly inhibited the production of nitric oxide and the expression of major inflammatory biomarkers such as inducible NO synthase, cyclooxygenase-2, interleukin (IL)-6, and IL-1β significantly. Based on these in vitro results, we investigated the anti-inflammatory properties of SJFE on osteoarthritis (OA) of the left hind knee joints induced by monosodium iodoacetate in rats. SJFE was orally administered to the rats with arthritis for 4 weeks, and the following results were obtained. The rats treated with SJFE exhibited a 24% improvement in the weight-bearing index of their affected legs, as well as reductions of 31.5% and 23.2% in serum levels of cartilage oligomeric matrix protein and C-terminal telopeptide 2, respectively. Additionally, Mankin’s score, an indicator used to assess the severity of joint cartilage damage, decreased by 2.75 points compared to the control with no treatment. These findings suggest that SJFE possesses anti-inflammatory properties and can alleviate symptoms of OA, indicating its potential to offer relief to individuals suffering from arthritis.

Spatiotemporal spike-centered averaging (st-SCA) allows for the visualization of spike-local field potential relationships across both temporal and spatial domains from microelectrode array recordings.

Abstract Infraslow activity (ISA) is a biomarker that has recently become of interest in the characterization of seizure recordings. Recent data from a small number of studies have suggested that the epileptogenic zone may be identified by the presence of ISA. Investigation of low frequency activity in clinical seizure recordings, however, has been hampered by technical limitations. EEG systems necessarily include a high-pass filter early in the measurement chain to remove large artifactual drifts that can saturate recording elements such as the amplifier. This filter, unfortunately, attenuates legitimately seizure-related low frequencies, making ISA difficult to study in clinical EEG recordings. In this study, we present a deconvolution-based digital inverse filter that allows recovery of attenuated low frequency activity in intracranial recordings of temporal lobe epilepsy patients. First, we show that the unit impulse response (UIR) of an EEG system can be characterized by differentiation of the system’s step response. As proof of method, we present several examples that show that the low frequency component of a high-pass filtered signal can be restored by deconvolution with the UIR. We then demonstrate that this method can be applied to biologically relevant signals including clinical EEG recordings obtained from seizure patients. Finally, we discuss how this method can be applied to study ISA to identify and assess the seizure onset zone.

Abstract Microfluidic organ-on-a-chip technologies have enabled construction of biomimetic physiologically and pathologically relevant models. This paper describes an injection molded microfluidic platform that utilizes a novel sequential edge-guided patterning method based on spontaneous capillary flow to realize three-dimensional co-culture models and form an array of micro-vascularized tissues (28 per 1 × 2-inch slide format). The MicroVascular Injection-Molded Plastic Array 3D Culture (MV-IMPACT) platform is fabricated by injection molding, resulting in devices that are reliable and easy to use. By patterning hydrogels containing human umbilical endothelial cells and fibroblasts in close proximity and allowing them to form vasculogenic networks, an array of perfusable vascularized micro-tissues can be formed in a highly efficient manner. The high-throughput generation of angiogenic sprouts was quantified and their uniformity was characterized. Due to its compact design (half the size of a 96-well microtiter plate), it requires small amount of reagents and cells per device. In addition, the device design is compatible with a high content imaging machine such as Yokogawa CQ-1. Furthermore, we demonstrated the potential of our platform for high-throughput phenotypic screening by testing the effect of DAPT, a chemical known to affect angiogenesis. The MV-IMPACT represent a significant improvement over our previous PDMS-based devices in terms of molding 3D co-culture conditions at much higher throughput with added reliability and robustness in obtaining vascular micro-tissues and will provide a platform for developing applications in drug screening and development.

Abstract Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch–JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the most promising candidate. Combined with further validation with real-time PCR, downregulation of NOTCH1 was statistically significant. Accordingly, we reverse-translated the significant finding from a surrogate tissue for neurons, and studied the behavioral profile of Notch1 +/− mice. We found a specific impairment in social novelty recognition, whereas other behaviors, such as sociability, novel object recognition and olfaction of social odors, were normal. This social novelty recognition deficit was male-specific and was rescued by rapamycin treatment. Based on the results from the animal model, we next tested whether patients with psychosis might have male-specific alterations in social cognition in association with the expression of NOTCH1 or JAG1. In our first episode psychosis cohort, we observed a specific correlation between the expression of JAG1 and a face processing measure only in male patients. The expression of JAG1 was not correlated with any other cognitive and symptomatic scales in all subjects. Together, although we acknowledge the pioneering and exploratory nature, the present work that combines both human and animal studies in a reciprocal manner suggests a novel role for the Notch–JAG pathway in a behavioral dimension(s) related to social cognition in psychotic disorders in a male-specific manner.

Chimeric antigen receptor (CAR)-T cells have revolutionized the treatment of multiple types of hematological malignancies, but have shown limited efficacy in patients with glioblastoma (GBM) or other solid tumors. This may be largely due to the immunosuppressive tumor microenvironment (TME) that compromises CAR-T cells’ delivery and antitumor activity. We previously showed that blocking vascular endothelial growth factor (VEGF) signaling can normalize tumor vessels in murine and human tumors, including GBM, breast, liver, and rectal carcinomas. Moreover, we demonstrated that vascular normalization can improve the delivery of CD8+ T cells and the efficacy of immunotherapy in breast cancer models in mice. In fact, the US FDA (Food and drug administration) has approved seven different combinations of anti-VEGF drugs and immune checkpoint blockers for liver, kidney, lung and endometrial cancers in the past 3 years. Here, we tested the hypothesis that anti-VEGF therapy can improve the delivery and efficacy of CAR-T cells in immunocompetent mice bearing orthotopic GBM tumors. We engineered two syngeneic mouse GBM cell lines (CT2A and GSC005) to express EGFRvIII—one of the most common neoantigens in human GBM—and CAR T cells to recognize EGFRvIII. We found that treatment with the anti-mouse VEGF antibody (B20) improved CAR-T cell infiltration and distribution throughout the GBM TME, delayed tumor growth, and prolonged survival of GBM-bearing mice compared with EGFRvIII-CAR-T cell therapy alone. Our findings provide compelling data and a rationale for clinical evaluation of anti-VEGF agents with CAR T cells for GBM patients.

The present study describes five newly recorded modern benthic foraminiferal species from the subtidal zone near Jeju Island and East China Sea (Korea). The newly recorded species (Karrerulina conversa, Rotaliammina trumbulli, Vertebralina striata, Pegidia dubia and Amphistegina radiata) belong to five families (Prolixoplectidae, Trochamminidae, Fischerinidae, Pegidiidae and Amphisteginidae), three orders (Lituolida, Miliolida and Rotaliida) and two classes (Globothalamea and Tubothalamea). All these five genera (Karrerulina, Rotaliammina, Vertebralina, Pegidia and Amphistegina) were also reported for the first time from Korean waters. Most of the examined specimens were highly consistent morphologically with previous records from southern China and Japan. Additionally, Amphistegina is one of the symbiont-bearing larger benthic foraminifera, known to be mainly distributed in tropical to warm subtropical waters. This study contributes to the expansion of data on the recent foraminiferal species diversity in Korean waters.

With the expansion of the application range of big data and artificial intelligence technologies, graph data have been increasingly used to analyze the relationships among objects. With the advancement of network technology and the spread of social network services, there has been an increasing need for a continuous query processing algorithm that can manage large-volume graph streams generated in real time. In this paper, a sliding-window-based continuous subgraph matching algorithm that can efficiently control graph streams is proposed. The proposed scheme uses a query processing technique based on trie indexing. It establishes an index based on a materialized view of similar queries and conducts continuous query processing based on the materialized view to perform continuous query processing efficiently. It also provides wildcard operations on vertices and edges to consider various query types. Moreover, in this study, a two-level cache technique that can manage frequently used subgraphs and subgraphs that may be used in the future is developed, to handle intermediate query results in the form of a materialized view. Cache replacement techniques based on statistical data are also presented to improve the performance of the developed cache technique. The excellent performance of the proposed algorithm is verified by a conducting independent performance evaluation and comparative performance evaluation.

We guide the use of organ-on-chip technology in tissue engineering applications. Organ-on-chip technology is a form of microengineered cell culture platform that elaborates the in-vivo like organ or tissue microenvironments. The organ-on-chip platform consists of microfluidic channels, cell culture chambers, and stimulus sources that emulate the in-vivo microenvironment. These platforms are typically engraved into an oxygen-permeable transparent material. Fabrication of these materials requires the use of microfabrication strategies, including soft lithography, 3D printing, and injection molding. Here we provide an overview of what is an organ-on-chip platform, where it can be used, what it is composed of, how it can be fabricated, and how it can be operated. In connection with this topic, we also introduce an overview of the recent applications, where different organs are modeled on the microscale using this technology.

Abstract Background Hypertension is one of the most important risk factors for cardiovascular disease (CVD) and a worldwide problem. Despite increases in the development of synthetic drugs for hypertension treatment, the rate of untreated and uncontrolled hypertension remains high. These drugs are effective, but can also cause side effects. Approximately 80% of the world population uses herbal medicines because of their low toxicity and better acceptability by the human body. Therefore, we attempted to identify natural medications for treating hypertension. The 70% ethanol extract of Angelica decursiva root (ADE) shows strong vasorelaxant potential, but no studies have investigated the mechanisms underlying the vasorelaxation effect of A. decursiva. Methods Dried root of A. decursiva was identified by DNA sequencing and was extracted once with 1 L 70% ethanol (EtOH) for 3 h in a reflux apparatus at 70 °C. ADE was evaluated for its vasorelaxant effects in rat thoracic aortas. Various inhibitors of ADE-induced vasorelaxation were used. Results ADE showed vasorelaxant effects on the intact and denuded endothelium of aortic rings pre-contracted with phenylephrine and KCl in Krebs-Henseleit solution. Tetraethylammonium and 4-aminopyridine did not alter ADE-induced vasorelaxation. However, the vasorelaxant effect of ADE was partially inhibited by pre-treatment with glibenclamide an ATP-sensitive K+ channel blocker. Furthermore, ADE concentration-dependently inhibited Ca2+ supplementation-induced vasoconstriction of aortic rings that had been pretreated with phenylephrine or KCl in Ca2+-free Krebs-Henseleit solution. Conclusions These results suggest that ADE-induced vasorelaxation occurred in an endothelium-independent manner. The vasorelaxant effects of ADE were correlated with blockade of the KATP channel and inhibition of Ca2+ influx via receptor-operative Ca2+ channels or voltage-dependent Ca2+ channels.

We describe a new agglutinated monothalamous foraminiferal species, Capsammina crassa sp. nov., based on integrated observations of the test morphology and the chemical characteristics of materials composing the test. The new species was found at a depth of

Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific ginsenosides through fermentation. In the study, we also evaluated the ability of fermented cultured wild ginseng root extract (HLJG0701-β) to inhibit acetylcholinesterase (AChE), as well as its neuroprotective effects and antioxidant activity. In invitro tests, HLJG0701-β inhibited AChE activity and exerted neuroprotective and antioxidant effects (showing increased catalyst activity but decreased reactive oxygen species concentration). In invivo tests, after HLJG0701-β was orally administered at doses of 0, 125, 250, and 500 mg/kg in an animal model of memory impairment, behavioral evaluation (Morris water maze test and Y-maze task test) was performed. The levels of AChE, acetylcholine (ACh), blood catalase (CAT), and malondialdehyde (MDA) in brain tissues were measured. The results showed that HLJG0701-β produced the best results at a dose of 250 mg/kg or more. The neuroprotective mechanism of HLJG0701-β was determined to involve the inhibition of AChE activity and a decrease in oxidative stress. In summary, both invitro and invivo tests confirmed that HJG0701-β administration can lead to memory improvement.

Korean plum (Prunus mume (Siebold) Siebold & Zucc.) has long been used as a health food or herbal medicine in Asia. Previous studies have shown that several plants of the genus Prunus have vasodilatory and antihypertensive effects; we hypothesized that P. mume branches may have a vasorelaxant effect. In this study, we evaluated the effects and action mechanism of 70% ethanol extract of P. mume branch (PMB) on isolated rat aortic rings. Inhibitors such as NG-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, methylene blue, indomethacin, atropine, tetraethylammonium chloride, glibenclamide, 4-aminopyridine and BaCl2 were used to investigate the mechanism of vasodilation responsible for the vascular relaxation. PMB (2−30 μg/mL) induced vasorelaxation in the presence of vascular endothelium, and all inhibitors used in this study affected the degree of relaxation. These results suggest that the vasorelaxant effect of PMB is endothelium-dependent and affects the nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin pathway, muscarinic receptor pathway, and potassium channels. Our study explains that PMB may be another approach to hypertension treatment to reduce the burden of cardiovascular disease.

Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a high-phosphate diet (HPD) in a mouse model of adenocarcinoma. K-rasLA1 mice were fed a normal diet (0.3% Pi) or an HPD (1% Pi) for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis), changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention.

[This corrects the article DOI: 10.1371/journal.pone.0077121.].

The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras (LA1) mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy.

The aim of this study is to investigate the automatic recognition and analysis of Jeju marine-life images using artificial intelligence (AI) technology. The dataset of marine-life images was prepared using tools such as Python, TensorFlow, and Google Colab (Google Colaboratory). We also developed models by training deep learning AI in image recognition to automatically recognize the species found in these images and extract their associated information, such as taxonomy, characteristics, and distribution. This study is innovative in that it uses deep learning technology combined with imagerecognition technology for marine biodiversity research. In addition, these results will lead to the development of the marine-life industry in Jeju by supporting marine environment monitoring and marine resource conservation. Furthermore, this study is anticipated to contribute to academic advancement, specifically in the study of marine species diversity. [ABSTRACT FROM AUTHOR]

Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]