Development of an in vitro coculture device for the investigation of host-microbe interactions via integrative multiomics approaches.

The commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host-Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco-2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell-cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells.

Anti-proliferation effects of Cistanches salsa on the progression of benign prostatic hyperplasia.

Cistanche salsa has been used in traditional medicine for the treatment of kidney deficiency, neurasthenia, sexual dysfunction diseases, and benign prostatic hyperplasia (BPH). The aim of this study was to investigate the mechanism by which C. salsa extract (CSE) elicits an anti-proliferative effect on the prostate tissue of BPH-induced rats. The effects of CSE on BPH were evaluated in terms of prostate weight, production of serum dihydrotestosterone (DHT), and the mRNA expression of 5α-reductase type 1 and type 2 in the prostate tissue of BPH-induced rats. In addition, hematoxylin and eosin (H&E) staining was performed for histological examination of prostate gland morphology, and protein expression levels in prostate tissue were investigated by western blot analysis. CSE treatment decreased prostate weight, serum DHT concentration, and the mRNA expression of 5α-reductase type 1 and type 2 in prostate tissue of BPH-induced rats. In addition, CSE treatment suppressed cell proliferation by regulating the expression levels of inflammatory-related proteins (inducible nitric oxide synthase and cyclooxygenase 2) and apoptosis-associated proteins (caspase-3 and Bcl-2 family proteins). CSE may be a potential therapeutic candidate for BPH owing to its ability to regulate the expression of inflammatory and apoptosis-related proteins.

Seebeck coefficient characterization of highly doped n- and p-type silicon nanowires for thermoelectric device applications fabricated with top-down approach.

A silicon nanowire one-dimensional thermoelectric device is presented as a solution to enhance thermoelectric performance. A top-down process is adopted for the definition of 50 nm silicon nanowires (SiNWs) and the fabrication of the nano-structured thermoelectric devices on silicon on insulator (SOl) wafer. To measure the Seebeck coefficients of 50 nm width n- and p-type SiNWs, a thermoelectric test structure, containing SiNWs, micro-heaters and temperature sensors is fabricated. Doping concentration is 1.0 x 10(20) cm(-3) for both for n- and p-type SiNWs. To determine the temperature gradient, a temperature coefficient of resistance (TCR) analysis is done and the extracted TCR value is 1750-1800 PPM x K(-1). The measured Seebeck coefficients are -127.583 microV x K(-1) and 141.758 microV x K(-1) for n- and p-type SiNWs, respectively, at room temperature. Consequently, power factor values are 1.46 mW x m(-1) x K(-2) and 1.66 mW x m(-1) x K(-2) for n- and p-type SiNWs, respectively. Our results indicate that SiNWs based thermoelectric devices have a great potential for applications in future energy conversion systems.

Effect of silicide/silicon hetero-junction structure on thermal conductivity and Seebeck coefficient.

We fabricated a thermoelectric device with a silicide/silicon laminated hetero-structure by using RF sputtering and rapid thermal annealing. The device was observed to have Ohmic characteristics by I-V measurement. The temperature differences and Seebeck coefficients of the proposed silicide/silicon laminated and bulk structure were measured. The laminated thermoelectric device shows suppression of heat flow from the hot to cold side. This is supported by the theory that the atomic mass difference between silicide and silicon creates a scattering center for phonons. The major impact of our work is that phonon transmission is suppressed at the interface between silicide and silicon without degrading electrical conductivity. The estimated thermal conductivity of the 3-layer laminated device is 126.2 +/- 3.7 W/m. K. Thus, by using the 3-layer laminated structure, thermal conductivity is reduced by around 16% compared to bulk silicon. However, the Seebeck coefficient of the thermoelectric device is degraded compared to that of bulk silicon. It is understood that electrical conductivity is improved by using silicide as a scattering center.

Characteristics of novel root-end filling material using epoxy resin and Portland cement.

OBJECTIVES: The aim of this study was to evaluate the physical properties and cytotoxicity of a novel root-end filling material (EPC) which is made from epoxy resin and Portland cement as a mineral trioxide aggregate (MTA) substitute. MATERIALS AND METHODS: EPC, developed as a root-end filling material, was compared with MTA and a mixture of AH Plus sealer and MTA (AMTA) with regard to the setting time, radio-opacity, and microleakage. Setting times were evaluated using Vicat apparatus. Digital radiographs were taken to evaluate the aluminium equivalent radio-opacity using an aluminium step wedge. Extracted single-rooted teeth were used for leakage test using methylene blue dye. After canal shaping and obturation, the apical 3-mm root was resected, and a root-end cavity with a depth of 3 mm was prepared. The root-end cavities were filled with MTA, AMTA, and EPC for 15 specimens in each of three groups. After setting in humid conditions for 24 h, the specimens were tested for apical leakage. For evaluation of the biocompatibility of EPC, cell (human gingival fibroblast) viability was compared for MTA and Portland cement by MTT assay, and cell morphological changes were compared for MTA and AH Plus by fluorescence microscopy using DAPI and F-actin staining. The setting time, radio-opacity, and microleakage were compared using one-way ANOVA and Scheffe's post hoc comparison, and the cytotoxicity was compared using the nonparametric Kruskal-Wallis rank sum test. Statistical significance was set at 95%. RESULTS: EPC had a shorter setting time and less microleakage compared with MTA (p < 0.05). EPC showed 5-mm aluminium thickness radio-opacity and similar biocompatibility to MTA. CONCLUSIONS: Under the conditions of this study, EPC, a novel composite made from a mixture of epoxy resin and Portland cement, was found to be a useful material for root-end filling, with favourable radio-opacity, short setting time, low microleakage, and clinically acceptable low cytotoxicity. CLINICAL RELEVANCE: The novel root-end filling material would be a potentially useful material for a surgical endodontic procedure with favourable properties.

PET: Parameter-efficient Knowledge Distillation on Transformer.

Given a large Transformer model, how can we obtain a small and computationally efficient model which maintains the performance of the original model? Transformer has shown significant performance improvements for many NLP tasks in recent years. However, their large size, expensive computational cost, and long inference time make it challenging to deploy them to resource-constrained devices. Existing Transformer compression methods mainly focus on reducing the size of the encoder ignoring the fact that the decoder takes the major portion of the long inference time. In this paper, we propose PET (Parameter-Efficient knowledge distillation on Transformer), an efficient Transformer compression method that reduces the size of both the encoder and decoder. In PET, we identify and exploit pairs of parameter groups for efficient weight sharing, and employ a warm-up process using a simplified task to increase the gain through Knowledge Distillation. Extensive experiments on five real-world datasets show that PET outperforms existing methods in machine translation tasks. Specifically, on the IWSLT'14 EN→DE task, PET reduces the memory usage by 81.20% and accelerates the inference speed by 45.15% compared to the uncompressed model, with a minor decrease in BLEU score of 0.27.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia.

Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose-stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations, while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1 min/1 min 5-21% cycling for 1 h), translating to improved insulin secretion. Moreover, blocking mitochondrial K(ATP) channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues.

Systematic prevention of bubble formation and accumulation for long-term culture of pancreatic islet cells in microfluidic device.

Reliable long-term cell culture in microfluidic system is limited by air bubble formation and accumulation. In this study, we developed a bubble removal system capable of both trapping and discharging air bubbles in a consistent and reliable manner. Combined with PDMS (Polydimethylsiloxane) hydrophilic surface treatment and vacuum filling, a microfluidic perifusion system equipped with the bubble trap was successfully applied for long-term culture of mouse pancreatic islets with no bubble formation and no flow interruption. In addition to demonstrating normal cell viability and islet morphology, post-cultured islets exhibited normal insulin secretion kinetics, intracellular calcium signaling, and changes in mitochondrial potentials in response to glucose challenge. This design could be easily adapted by other microfluidic systems due to its simple design, ease of fabrication, and portability.

An integrative multiomics approach to characterize anti-adipogenic and anti-lipogenic effects of Akkermansia muciniphila in adipocytes.

The cellular components of Akkermansia muciniphila are considered potential biotherapeutics for the improvement of obesity, diabetes, and metabolic diseases. However, the molecular-based mechanism of A. muciniphila for treatment of obesity, which can provide important evidence for human research, has rarely been explored. Here, we applied integrative multiomics approaches to investigate the underlying molecular mechanism involved in obesity treatment by A. muciniphila. First, the treatment with a cell lysate of A. muciniphila reduced lipid accumulation in 3T3-L1 cells and downregulated the mRNA expression of proteins involved in adipogenesis and lipogenesis. Our proteomic results revealed that A. muciniphila decreased the expression of proteins involved in fat cell differentiation, fatty acid metabolism, and energy metabolism in adipocytes. Moreover, A. muciniphila significantly reduced the level of metabolites related to glycolysis, the TCA cycle, and ATP in adipocytes. Interestingly, serine protease inhibitor A3 (SERPINA3) homologs were overexpressed in the 3T3-L1 cells treated with A. muciniphila. Small interfering RNA (siRNA) transfection demonstrated that A. muciniphila upregulates SERPINA3G expression and inhibits lipogenesis in adipocytes. Taken together, our multiomics-based approaches enabled to uncover the molecular mechanism of A. muciniphila for treatment of obesity and provide potent anti-lipogenic agents.

An Integrative Multiomics Approach to Characterize Prebiotic Inulin Effects on Faecalibacterium prausnitzii.

Faecalibacterium prausnitzii, a major commensal bacterium in the human gut, is well known for its anti-inflammatory effects, which improve host intestinal health. Although several studies have reported that inulin, a well-known prebiotic, increases the abundance of F. prausnitzii in the intestine, the mechanism underlying this effect remains unclear. In this study, we applied liquid chromatography tandem mass spectrometry (LC-MS/MS)-based multiomics approaches to identify biological and enzymatic mechanisms of F. prausnitzii involved in the selective digestion of inulin. First, to determine the preference for dietary carbohydrates, we compared the growth of F. prausnitzii in several carbon sources and observed selective growth in inulin. In addition, an LC-MS/MS-based intracellular proteomic and metabolic profiling was performed to determine the quantitative changes in specific proteins and metabolites of F. prausnitzii when grown on inulin. Interestingly, proteomic analysis revealed that the putative proteins involved in inulin-type fructan utilization by F. prausnitzii, particularly ß-fructosidase and amylosucrase were upregulated in the presence of inulin. To investigate the function of these proteins, we overexpressed bfrA and ams, genes encoding ß-fructosidase and amylosucrase, respectively, in Escherichia coli, and observed their ability to degrade fructan. In addition, the enzyme activity assay demonstrated that intracellular fructan hydrolases degrade the inulin-type fructans taken up by fructan ATP-binding cassette transporters. Furthermore, we showed that the fructose uptake activity of F. prausnitzii was enhanced by the fructose phosphotransferase system transporter when inulin was used as a carbon source. Intracellular metabolomic analysis indicated that F. prausnitzii could use fructose, the product of inulin-type fructan degradation, as an energy source for inulin utilization. Taken together, this study provided molecular insights regarding the metabolism of F. prauznitzii for inulin, which stimulates the growth and activity of the beneficial bacterium in the intestine.

Investigation of metabolic crosstalk between host and pathogenic Clostridioides difficile via multiomics approaches.

Clostridioides difficile is a gram-positive anaerobic bacterium that causes antibiotic-associated infections in the gut. C. difficile infection develops in the intestine of a host with an imbalance of the intestinal microbiota and, in severe cases, can lead to toxic megacolon, intestinal perforation, and even death. Despite its severity and importance, however, the lack of a model to understand host-pathogen interactions and the lack of research results on host cell effects and response mechanisms under C. difficile infection remain limited. Here, we developed an in vitro anaerobic-aerobic C. difficile infection model that enables direct interaction between human gut epithelial cells and C. difficile through the Mimetic Intestinal Host-Microbe Interaction Coculture System. Additionally, an integrative multiomics approach was applied to investigate the biological changes and response mechanisms of host cells caused by C. difficile in the early stage of infection. The C. difficile infection model was validated through the induction of disaggregation of the actin filaments and disruption of the intestinal epithelial barrier as the toxin-mediated phenotypes following infection progression. In addition, an upregulation of stress-induced chaperones and an increase in the ubiquitin proteasomal pathway were identified in response to protein stress that occurred in the early stage of infection, and downregulation of proteins contained in the electron transfer chain and ATP synthase was observed. It has been demonstrated that host cell energy metabolism is inhibited through the glycolysis of Caco-2 cells and the reduction of metabolites belonging to the TCA cycle. Taken together, our C. difficile infection model suggests a new biological response pathway in the host cell induced by C. difficile during the early stage of infection at the molecular level under anaerobic-aerobic conditions. Therefore, this study has the potential to be applied to the development of future therapeutics through basic metabolic studies of C. difficile infection.

Multi-omics based characterization of antibiotic response in clinical isogenic isolates of methicillin-susceptible/-resistant Staphylococcus aureus.

As demands for new antibiotics and strategies to control methicillin-resistant Staphylococcus aureus (MRSA) increase, there have been efforts to obtain more accurate and abundant information about the mechanism of the bacterial responses to antibiotics. However, most of the previous studies have investigated responses to antibiotics without considering the genetic differences between MRSA and methicillin-susceptible S. aureus (MSSA). Here, we initially applied a multi-omics approach into the clinical isolates (i.e., S. aureus WKZ-1 (MSSA) and S. aureus WKZ-2 (MRSA)) that are isogenic except for the mobile genetic element called staphylococcal cassette chromosome mec (SCCmec) type IV to explore the response to ß-lactam antibiotics (oxacillin). First, the isogenic pair showed a similar metabolism without oxacillin treatment. The quantitative proteomics demonstrated that proteins involved in peptidoglycan biosynthesis (MurZ, PBP2, SgtB, PrsA), two-component systems (VrsSR, WalR, SaeSR, AgrA), oxidative stress (MsrA1, MsrB), and stringent response (RelQ) were differentially regulated after the oxacillin treatment of the isogenic isolates. In addition, targeted metabolic profiling showed that metabolites belonging to the building blocks (lysine, glutamine, acetyl-CoA, UTP) of peptidoglycan biosynthesis machinery were specifically decreased in the oxacillin-treated MRSA. These results indicate that the difference in metabolism of this isogenic pair with oxacillin treatment could be caused only by SCCmec type IV. Understanding and investigating the antibiotic response at the molecular level can, therefore, provide insight into drug resistance mechanisms and new opportunities for antibiotics development.

Multi-omics characterization of the osmotic stress resistance and protease activities of the halophilic bacterium Pseudoalteromonas phenolica in response to salt stress.

The halophilic bacterium Pseudoalteromonas phenolica is well known as a promising candidate that enables the recycling of organic wastes at high salinity. However, for industrial applications of P. phenolica further research is required to explore the biological mechanism for maximizing the activities and productivities of this bacterium. In this study, we investigated the osmotic stress resistance and specific protease activities of P. phenolica in a normal-salt medium (0.3 M NaCl) and high-salt medium (1 M NaCl) based on intra- and extracellular multi-omics approaches. Proteins related to betaine and proline biosynthesis were increased under high salt stress. The targeted metabolite analysis found that proline was overproduced and accumulated outside the cell at high salinity, and betaine was accumulated in the cell by activation of biosynthesis as well as uptake. In addition, extracellular serine proteases were shown to be upregulated in response to salt stress by the extracellular proteomic analysis. The specific proteolytic activity assay indicated that the activities of serine proteases, useful enzymes for the recycling of organic wastes, were increased remarkably under high salt stress. Our results suggest that betaine and proline are key osmoprotectant metabolites of P. phenolica, and they can be used for the improvement of protease production and P. phenolica activities for the recycling of high-salt organic wastes in the future.

Therapeutic Effects of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Combined with Cartilage Acellular Matrix Mediated Via Bone Morphogenic Protein 6 in a Rabbit Model of Articular Cruciate Ligament Transection.

Osteoarthritis (OA) is a general joint disease. Cartilage damage is associated with a decrease in the density of chondrocytes. Mesenchymal stem cells (MSCs) differentiate into adipocytes, osteocytes and chondrocytes, and are an excellent source of cell therapy. Cartilage-derived extracellular matrix (ECM) promotes chondrogenesis of MSCs. However, the role of MSCs stimulated by ECM is not well known in OA. The purpose of this study is to determine the role of specific factors generated by the application of ECM and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in managing OA symptoms. Cartilage acellular matrix (CAM), which is a cartilage-derived ECM, was used to promote the chondrogenesis of UCB-MSCs. Induced MSCs were analyzed using chondrogenic markers (aggrecan, collagen type 2, and SOX9) and bone morphogenic protein 6 (BMP6). BMP6 is known to be involved in early chondrogenesis of MSCs. As a result, treatment with CAM significantly increased the expression of chondrogenic markers and BMP6 in UCB-MSCs. Treatment with recombinant human BMP6 also dramatically increased the levels of chondrogenic markers in UCB-MSCs. In addition, UCB-MSCs and CAM were used to evaluate OA symptom improvement in a rabbit articular cruciate ligament transection (ACLT) model. Application of UCB-MSCs and CAM enhanced not only the structure and synthesis of proteoglycan and collagen type 2 but also anti-inflammatory effects in both rabbit joint and synovial fluid. Moreover, the detection of human cells and involvement of BMP6 were confirmed in rabbit cartilage tissues. This study indicates that therapeutic potential of UCB-MSCs with CAM is mediated via BMP6 in OA.

Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage.

About 50% of humans with aneurysmal subarachnoid hemorrhage (SAH) die and many survivors have neurological and neurobehavioral dysfunction. Animal studies usually focused on cerebral vasospasm and sometimes neuronal injury. The difference in endpoints may contribute to lack of translation of treatments effective in animals to humans. We reviewed prior animal studies of SAH to determine what neurological and neurobehavioral endpoints had been used, whether they differentiated between appropriate controls and animals with SAH, whether treatment effects were reported and whether they correlated with vasospasm. Only a few studies in rats examined learning and memory. It is concluded that more studies are needed to fully characterize neurobehavioral performance in animals with SAH and assess effects of treatment.

Effect of fibroblast co-culture on the proliferation, viability and drug response of colon cancer cells.

Interactions between cancer cells and the surrounding fibroblasts serve an important role in cancer proliferation. Colon cancer co-culture model with colon fibroblasts and two metastatic models with lung and skin fibroblasts were established, and the co-culture effects on colon cancer cell proliferation, apoptosis and drug response were evaluated. Co-culture with CCD-18Co and BJ reduces SW480 cell proliferation by 4.2 and 5.3%, respectively, while WI-38 acts as a positive regulator and increases SW480 cell proliferation by 36%. CCD-18Co and BJ co-culture can also enhance XAV939 potency against SW480 cells by 16.8 and 27.3%; however, WI-38 co-culture reduces the effect of XAV939 by 38.2%. The present results suggest that, depending on fibroblast type, co-culture can have a positive/negative influence on colon cancer growth; therefore, care should be taken when considering fibroblasts as a target for future cancer therapies.

Therapeutic effect of long-interval repeated intravenous administration of human umbilical cord blood-derived mesenchymal stem cells in DBA/1 mice with collagen-induced arthritis.

Rheumatoid arthritis (RA) is a common inflammatory chronic disease. It has been reported that mesenchymal stem cells (MSCs) have the effect of immune suppression in collagen-induced arthritis (CIA) mice model. However, the in vivo therapeutic effect from the long-interval repeated intravenous administration of human umbilical cord blood-derived (hUCB)-MSCs had not been investigated in CIA mice model. This study was undertaken to investigate the effects of long-interval repeated intravenous administration of hUCB-MSCs at different doses in CIA mice model. Mice were intravenously injected with three different doses of hUCB-MSCs once every 2 weeks for three times. RA severity was assessed by clinical joint score and histologic analysis including hematoxylin and eosin staining, safranin-O staining, and toluidine blue staining. We used real-time polymerase chain reaction and flow cytometry to quantify differences in inflammatory cytokines and Tregs. Mice treated with hUCB-MSCs showed significant improvement in clinical joint score. Histologic analysis revealed that hUCB-MSCs definitely reduced joint inflammation, cartilage damage, and formation of pannus in multimedium and multihigh groups. These hUCB-MSCs also significantly decreased IL-1 beta protein levels in multimedium and multihigh groups and IL-6 protein levels in all hUCB-MSCs-treated groups. Furthermore, mRNA levels of IL-1 beta and IL-6 were decreased significantly in all hUCB-MSCs-treated groups, whereas the expression of anti-inflammatory cytokine IL-10 was increased in the multihigh group. Tregs known as suppressor T cells were also significantly increased in the multihigh group. Our findings suggest that long-interval repeated intravenous administration of hUCB-MSCs has therapeutic effects by improving symptoms of RA in CIA mice model in a dose-dependent manner.

Non-clinical pharmacokinetic behavior of ginsenosides.

Ginsenosides, the major active ingredients of ginseng and other plants of the genus Panax, have been used as natural medicines in the East for a long time; in addition, their popularity in the West has increased owing to their various beneficial pharmacological effects. There is therefore a wealth of literature regarding the pharmacological effects of ginsenosides. In contrast, there are few comprehensive studies that investigate their pharmacokinetic behaviors. This is because ginseng contains the complicated mixture of herbal materials as well as thousands of constituents with complex chemical properties, and ginsenosides undergo multiple biotransformation processes after administration. This is a significant issue as pharmacokinetic studies provide crucial data regarding the efficacy and safety of compounds. Moreover, there have been many difficulties in the development of the optimal dosage regimens of ginsenosides and the evaluation of their interactions with other drugs. Therefore, this review details the pharmacokinetic properties and profiles of ginsenosides determined in various animal models administered through different routes of administration. Such information is valuable for designing specialized delivery systems and determining optimal dosing strategies for ginsenosides.

Location of the umbilicus in Korean women and its changes after breast reconstruction with an ipsilateral pedicled rectus abdominis musculocutaneous flap.

BACKGROUND: The umbilicus makes an important contribution to the natural appearance of the abdomen. To date, studies on its position in Korean women are lacking, and no standards have been established. The purpose of this study was to investigate the position of umbilicus in Korean women and to review changes in its position after ipsilateral pedicled rectus abdominis musculocutaneous (IP-RAM) flap. METHODS: This research consisted of two studies. In first study, 100 females who visited the emergency department with gastroenteritis between 2007 and 2011 were included. In second study, 40 women who underwent IP-RAM flap in the same period were included. Using abdominal computed tomography, we measured the distance between xiphoid process and umbilicus, represented by value a, and the distance between umbilicus and symphysis pubis, represented by value b. Thus, the location of the umbilicus was represented by the ratio a/b. The data were analyzed using Pearson correlation test and paired t-test. RESULTS: In study 1, the mean value of a/b was 1.07. Pearson correlation test revealed a significant correlation between age and a/b. In study 2, the mean value of a/b was 1.16 in preoperative measurements and 1.01 in postoperative measurements. The paired t-test showed a significant difference between preoperative and postoperative measurements, indicating cephalic migration of the umbilicus after surgery. CONCLUSIONS: The natural position of the umbilicus showed caudal migration with aging. Additionally, in a comparison of preoperative and postoperative measurements in patients who underwent IP-RAM flap, cephalic migration of the umbilicus was observed after surgery.