A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling.

In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal and pericentral axis. How the mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combine intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We find that periportal and pericentral mitochondria are morphologically and functionally distinct; beta-oxidation is elevated in periportal regions, while lipid synthesis is predominant in the pericentral mitochondria. In addition, comparative phosphoproteomics reveals spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifts mitochondrial phenotypes in the periportal and pericentral regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.

Short-term exposure to ambient air pollution and injuries due to external causes according to intentions and mechanisms.

Although injuries are a leading cause of death and affect the life expectancy of individuals who live with disabilities globally, the potential role of air pollution exposure on injuries due to external causes has received little scientific attention, especially compared with that given to the association of air pollution and non-external causes of morbidity and mortality. We investigated the association between emergency department visits for externally caused injuries and short-term exposure to major ambient air pollutants, with focus on the intentions and mechanisms of injuries. We identified 2,049,855 injured patients in Seoul, South Korea between 2008 and 2016 using the National Emergency Database. Daily short-term exposure to air pollution including particles <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) was estimated based on hourly concentrations. We employed a time-stratified case-crossover study design using a conditional Poisson regression model adjusted for meteorological variables, influenza epidemics, and holidays. Immediate exposure (lag 0) to most pollutants significantly increased the risk of total injuries (PM2.5, 0.42 %; NO2, 0.68 %; SO2, 1.05 %; CO, 0.57 %; O3, 1.86 % per interquartile range increment), and the associations differed according to the intention and mechanism of injury. Unintentional and assault injuries were significantly associated with air pollution exposure, whereas self-harm injuries showed no association. In mechanism-specific analyses, injuries caused by falls, blunt objects, penetration, traffic accidents, machinery, and slips were associated with specific air pollutants, even in the co-pollutant models. The associations were stronger in injured patients aged <15 years, and in males than in their counterparts. Our results suggest that short-term air pollution exposure might play a role in the risk of externally caused injuries and the association may differ depending on the intention and mechanism of injury, which provide important evidence for injury prevention and air quality strategies.

GPCR Screening Reveals that the Metabolite Receptor HCAR3 Regulates Epithelial Proliferation, Migration, and Cellular Respiration.

Epithelial cells in the skin and other tissues rely on signals from their environment to maintain homeostasis and respond to injury, and GPCRs play a critical role in this communication. A better understanding of the GPCRs expressed in epithelial cells will contribute to understanding the relationship between cells and their niche and could lead to developing new therapies to modulate cell fate. This study used human primary keratinocytes as a model to investigate the specific GPCRs regulating epithelial cell proliferation and differentiation. We identified 3 key receptors-HCAR3, LTB4R, and GPR137-and found that knockdown of these receptors led to changes in numerous gene networks that are important for maintaining cell identity and promoting proliferation while inhibiting differentiation. Our study also revealed that the metabolite receptor HCAR3 regulates keratinocyte migration and cellular metabolism. Knockdown of HCAR3 led to reduced keratinocyte migration and respiration, which could be attributed to altered metabolite use and aberrant mitochondrial morphology caused by the absence of the receptor. This study contributes to understanding the complex interplay between GPCR signaling and epithelial cell fate decisions.

The Effect of Biomimetic Remineralization of Calcium Phosphate Ion Clusters-Treated Enamel Surfaces on Bracket Shear Bond Strength.

Purpose: To evaluate the remineralization effect of calcium phosphate ion clusters (CPICs) on demineralized enamel surfaces and their effects on bracket shear bond strength. Patients and Methods: Extracted premolars were prepared in resin blocks. The samples in the form of resin blocks were divided into five experimental groups: control group, demineralized group, and groups of CPIC solution treatment for 30, 60, and 90s. The specimens were examined using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), microhardness testing, micro-computed tomography (micro-CT) assessment, shear bond strength (SBS) test, and adhesive remnant index (ARI) score. Results: The SEM images revealed epitaxial growth of enamel and a decrease in the thickness of the demineralized enamel layer when treated with CPIC solution. The EDX analysis revealed an increase in the Ca/P ratio in the CPIC-treated groups. The microhardness value significantly increased when treated with CPICs; however, it showed a lower value than that of the sound enamel groups. As a result of the micro-CT test, radiolucency decreased gradually as the CPIC treatment time increased. The SBS test and ARI score results showed an improvement in bonding stability after treatment with CPICs. Conclusion: We demonstrated an enamel biomodification approach using CPIC solution treatment, which is a promising strategy for enamel remineralization. Specifically, remineralization of demineralized enamel improves the orthodontic bracket SBS.

Effects of dietary trace mineral levels on physiological responses, reproductive performance, litter performance, blood profiles, and milk composition in gestating sows.

OBJECTIVE: This study was conducted to evaluate the effects of optimal trace mineral levels on the physiological responses, reproductive performance, litter performance, blood profiles and milk composition in gestating sows. METHODS: A total of 59 multiparous sows (Yorkshire×Landrace) with similar body weight (BW), backfat thickness (BF), and parity were assigned to one of four treatments with 14 or 15 sows per treatment using a completely randomized design. The treatments were 100% (M1), 300% (M3), 600% (M6), and 900% (M9) of the National Research Council (NRC) Nutrient Requirements of Swine. During lactation period, all the sows were fed the same commercial lactation diet. RESULTS: No significant differences were observed in the BW, BF, reproductive performance, milk composition, or growth performance of the piglets. On day 70 of gestation, the serum zinc concentration showed a quadratic response to M6 treatment (quadratic, p<0.05). Moreover, as the dietary mineral levels increased, the zinc concentration increased linearly at 110 days of gestation (linear, p<0.05). Furthermore, copper and iron concentrations in the serum of sows at 24 h postpartum decreased linearly when high levels of dietary minerals were provided (linear, p<0.05). In the serum of piglets, serum zinc concentrations decreased linearly (linear, p<0.05), and iron concentration showed a quadratic response (quadratic, p<0.05) with an increase in trace mineral premix levels in gestation diets. CONCLUSION: The current trace mineral requirements of NRC (2012) are suitable for gestating sows, and the addition of dietary mineral levels in the gestating diet did not show any improvements during the gestation and lactation periods.

A GPCR screening in human keratinocytes identifies that the metabolite receptor HCAR3 controls epithelial proliferation, migration, and cellular respiration.

Epithelial cells in the skin and other tissues rely on signals from their environment to maintain homeostasis and respond to injury, and G protein-coupled receptors (GPCRs) play a critical role in this communication. A better understanding of the GPCRs expressed in epithelial cells will contribute to understanding the relationship between cells and their niche and could lead to developing new therapies to modulate cell fate. This study used human primary keratinocytes as a model to investigate the specific GPCRs regulating epithelial cell proliferation and differentiation. We identified three key receptors, hydroxycarboxylic acid-receptor 3 (HCAR3), leukotriene B4-receptor 1 (LTB4R), and G Protein-Coupled Receptor 137 (GPR137) and found that knockdown of these receptors led to changes in numerous gene networks that are important for maintaining cell identity and promoting proliferation while inhibiting differentiation. Our study also revealed that the metabolite receptor HCAR3 regulates keratinocyte migration and cellular metabolism. Knockdown of HCAR3 led to reduced keratinocyte migration and respiration, which could be attributed to altered metabolite use and aberrant mitochondrial morphology caused by the absence of the receptor. This study contributes to understanding the complex interplay between GPCR signaling and epithelial cell fate decisions.

A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling.

In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal (PP) and pericentral (PC) axis. How these mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combined intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We found that PP and PC mitochondria are morphologically and functionally distinct; beta-oxidation was elevated in PP regions, while lipid synthesis was predominant in the PC mitochondria. In addition, comparative phosphoproteomics revealed spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifted mitochondrial phenotypes in the PP and PC regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.

Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.

Metabolic programs contribute to hematopoietic stem and progenitor cell (HSPC) fate, but it is not known whether the metabolic regulation of protein synthesis controls HSPC differentiation. Here, we show that SLC7A1/cationic amino acid transporter 1-dependent arginine uptake and its catabolism to the polyamine spermidine control human erythroid specification of HSPCs via the activation of the eukaryotic translation initiation factor 5A (eIF5A). eIF5A activity is dependent on its hypusination, a posttranslational modification resulting from the conjugation of the aminobutyl moiety of spermidine to lysine. Notably, attenuation of hypusine synthesis in erythroid progenitors, by the inhibition of deoxyhypusine synthase, abrogates erythropoiesis but not myeloid cell differentiation. Proteomic profiling reveals mitochondrial translation to be a critical target of hypusinated eIF5A, and accordingly, progenitors with decreased hypusine activity exhibit diminished oxidative phosphorylation. This affected pathway is critical for eIF5A-regulated erythropoiesis, as interventions augmenting mitochondrial function partially rescue human erythropoiesis under conditions of attenuated hypusination. Levels of mitochondrial ribosomal proteins (RPs) were especially sensitive to the loss of hypusine, and we find that the ineffective erythropoiesis linked to haploinsufficiency of RPS14 in chromosome 5q deletions in myelodysplastic syndrome is associated with a diminished pool of hypusinated eIF5A. Moreover, patients with RPL11-haploinsufficient Diamond-Blackfan anemia as well as CD34+ progenitors with downregulated RPL11 exhibit a markedly decreased hypusination in erythroid progenitors, concomitant with a loss of mitochondrial metabolism. Thus, eIF5A-dependent protein synthesis regulates human erythropoiesis, and our data reveal a novel role for RPs in controlling eIF5A hypusination in HSPCs, synchronizing mitochondrial metabolism with erythroid differentiation.

Location matters: cellular heterogeneity in the hepatic lobule and hepatocellular carcinoma.

Tumor heterogeneity is a hallmark of cancer but a challenging problem to dissect mechanistically. Less recognized is that cells within normal tissues are also remarkably diverse. Hepatocytes are a great example because their spatial positioning and the local microenvironment govern their genetic heterogeneity. Recent studies show that primary liver tumors display heterogeneity similar to that observed in the normal tissue providing clues to the cellular precursor of the tumor and how variations in the lobule microenvironment support tumor formation and aggressiveness. Identifying the principles that control cellular diversity in a healthy liver may highlight potential mechanisms driving hepatic tumor heterogeneity.

Effects of ß-glucan with vitamin E supplementation on the physiological response, litter performance, blood profiles, immune response, and milk composition of lactating sows.

OBJECTIVE: This study was conducted to evaluate the effects of ß-glucan with vitamin E supplementation on the physiological response, litter performance, blood profiles, immune response, and milk composition of lactating sows. METHODS: A total of 50 multiparous F1 sows (Yorkshire×Landrace) with an average body weight (BW) of 233.6±4.30 kg and an average parity of 4.00±0.307 and their litters were used in this experiment. All sows were allotted to one of five treatments, taking into consideration BW, backfat thickness, and parity in a completely randomized design with 10 replicates. The experimental diets included a corn-soybean meal-based basal diet with or without 0.1% or 0.2% ß-glucan and 110 IU vitamin E/kg diet. RESULTS: All treatments added with ß-glucan or vitamin E were statistically higher in the average daily feed intake (ADFI) of lactating sows compared to those of the control (Diet, p<0.01). Additionally, the ADFI of lactating sows was significantly higher in the groups supplemented with 0.1% ß-glucan compared to 0.2% ß-glucan (BG, p<0.01). There was an increasing trend in piglet weight at weaning (BG, p = 0.07), litter weight at the 21st day of lactation (BG, p = 0.07) and litter weight gain (BG, p = 0.08) in groups supplemented with 0.1% ß-glucan. The addition of 110 IU vitamin E/kg diet increased vitamin E concentration significantly in lactating sows (VE, p<0.01) and exhibited a trend for higher concentrations of vitamin E (VE, p = 0.09) in piglets. Adding 0.1% ß-glucan compared to 0.2% ß-glucan induced a decrease in the concentration of tumor necrosis factor-α in lactating sows (BG, p = 0.06) and in piglets (BG, p = 0.09) on the 21st day of lactation. There were no significant differences in the milk composition of sows. CONCLUSION: Adding 0.1% ß-glucan and 110 IU vitamin E/kg to a lactating sow's diet was beneficial to the growth performance of piglets by leading to an increase in the feed intake of sows and efficiently supplying vitamin E to both the sows and piglets.

Association between depression and quality of life in stroke patients: The Korea National Health and Nutrition Examination Survey (KNHANES) IV-VII (2008-2018).

BACKGROUND: Stroke and depression are common diseases that affect quality of life (QoL). Although some recent studies have investigated the association between the two diseases, studies that examined the association between stroke, depression, and QoL are rare, with large-scale national-level studies lacking. We aimed to investigate the association between depression and QoL in stroke patients. METHODS: Data from the Korea National Health and Nutrition Examination Survey (KNHANES) IV-VII conducted in 2008-2018 were used, and 45,741 adults who were aged >40 years and had no missing data for stroke and depression were included in the analysis. The participants were first grouped by prevalence of stroke, and further divided by prevalence of depression. RESULTS: The overall prevalence of stroke was 3.2%, and the incidence was 9% higher in men than in women. Multiple logistic regression was performed after adjusting for demographic factors, health-related factors, and disease-related factors. The results confirmed that the stroke group with depression had a lower overall health-related quality of life, measured using EQ-5D, score compared to the stroke group without depression (-0.15). Moreover, the concurrent stroke and depression treatment group had the highest OR of 7.28 (95% CI 3.28-16.2) for the anxiety/depression domain. CONCLUSION: Depression was strongly associated with QoL in stroke patients. This association was more evident in stroke patients undergoing treatment for depression. Thus, clinical approaches that take QoL into consideration are needed for stroke patients with depression.

LKB1 acts as a critical brake for the glucagon-mediated fasting response.

As important as the fasting response is for survival, an inability to shut it down once nutrients become available can lead to exacerbated disease and severe wasting. The liver is central to transitions between feeding and fasting states, with glucagon being a key initiator of the hepatic fasting response. However, the precise mechanisms controlling fasting are not well defined. One potential mediator of these transitions is liver kinase B1 (LKB1), given its role in nutrient sensing. Here, we show LKB1 knockout mice have a severe wasting and prolonged fasting phenotype despite increased food intake. By applying RNA sequencing and intravital microscopy, we show that loss of LKB1 leads to a dramatic reprogramming of the hepatic lobule through robust up-regulation of periportal genes and functions. This is likely mediated through the opposing effect that LKB1 has on glucagon pathways and gene expression. Conclusion: Our findings show that LKB1 acts as a brake to the glucagon-mediated fasting response, resulting in "periportalization" of the hepatic lobule and whole-body metabolic inefficiency. These findings reveal a mechanism by which hepatic metabolic compartmentalization is regulated by nutrient-sensing.

Intravital Microscopy for the Study of Hepatic Glucose Uptake.

The liver is central in maintaining glucose homeostasis. Indeed, impaired hepatic glucose uptake has been implicated in the development of hyperglycemia in type II diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). However, current approaches to evaluate glucose mobilization rely on indirect measurements that do not provide spatial and temporal information. Here, we describe confocal-based intravital microscopy (IVM) of the liver that allows the identification of hepatocyte spatial organization and glucose transport. Specifically, we describe a method to fluorescently label hepatic landmarks to identify different compartments within the liver. In addition, we outline an in vivo fluorescent glucose uptake assay to quantitatively measure glucose mobilization in space and time. These protocols allow direct investigation of hepatic glycemic control and can be further applied to murine models of liver disease. © Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Mouse surgical procedure and positioning for liver intravital imaging Basic Protocol 2: Fluorescent labeling and intravital imaging of mouse hepatic compartments Basic Protocol 3: Mouse hepatic glucose uptake assay and intravital imaging analysis.

Changes in renal function and predictors affecting renal outcome of living kidney donors: a nationwide prospective cohort study.

AIM: The safety of donors is an important issue in living donor kidney transplantation. We investigated serial changes in renal function and predictors affecting the renal outcome of living kidney donors. METHODS: We obtained the data of 456 kidney donors registered to the Korean Organ Transplantation Registry from 2014 to 2016. The estimated glomerular filtration rate (eGFR) changes according to the development of incident chronic kidney disease (CKD) and factors related to CKD were analysed. CKD was defined as an eGFR <60 ml/min/1.73 m2 or the presence of proteinuria or albuminuria. The change in eGFR over time was analysed using a linear mixed model. RESULTS: At 2 years after kidney donation, 21.7% of the donors (99/456) developed CKD. Annual eGFR changes after nephrectomy were 2.2 ml/min/1.73 m2 /year in donors without CKD, and - 0.4 ml/min/1.73 m2 /year in donors with CKD. Higher systolic blood pressure was associated with higher risk of CKD (odds ratio [OR] 1.322 per 10 mmHg increment, 95% confidence interval [CI] 1.036-1.686, p = .025). Higher pre-donation eGFR (OR 0.906 per 1 ml/min/1.73 m2 increment, 95% CI 0.876-0.936, p < .001) and higher ratio of eGFR at discharge to pre-donation (OR 0.603 per 0.1 increment, 95% CI 0.426-0.849, p = .004) were related to lower risk of CKD. CONCLUSION: Kidney donors without incident CKD at 2 years after donation showed gradual increases in eGFR, whereas donors with CKD had relatively constant eGFR. A low ratio of eGFR at discharge after nephrectomy to baseline was a risk factor of CKD.

15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury.

The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin.

Effect of ambulatory blood pressure monitoring guided antihypertensive treatment on renal progression in patients with chronic kidney disease: a randomized comparative study.

OBJECTIVES: Adequate blood pressure (BP) control is pivotal for managing chronic kidney disease (CKD). The optimal approach for monitoring BP to delay CKD progression is not yet clear. METHODS: Patients with hypertension and CKD stage 3-4 were randomized into ambulatory blood pressure monitoring (ABPM) or office BP groups. All patients had ABPM at baseline and 18 months, and the ABPM group additionally underwent ABPM at 3 and 6 months. Each ABPM result was notified only for the ABPM group. The BP target was daytime ABP less than 135/85 mmHg for the ABPM group and office BP less than 140/90 mmHg for the office BP group. The primary outcome was decrease in estimated glomerular filtration rate (eGFR) during 18 months. RESULTS: A total of 146 patients were randomized into the ABPM (n = 69) and office BP groups (n = 77). Although office BP was comparable in the two groups at baseline, daytime ABP was higher in the ABPM group (median 140 vs. 132 mmHg). Initial eGFR was 35.7 ±â€Š12.5 ml/min per 1.73 m2 in the ABPM group and 34.6 ±â€Š12.0 ml/min per 1.73 m2 in the office BP group. eGFR change was -5.5 [95% confidence interval (95% CI) -7.7 to  -3.4] ml/min per 1.73 m2 in the ABPM group and -5.0 (95% CI -6.9 to -3.0) ml/min per 1.73 m2 in the office BP group (P = 0.704). Renal events occurred in 10 patients (15.6%) from the ABPM group and five (7.1%) from the office BP group (P = 0.120). CONCLUSION: The present study did not show a beneficial effect of ABPM for controlling hypertension in CKD compared with conventional office BP monitoring in terms of renal outcomes.

Association between Dialysis Adequacy and Cognition in Patients with Peritoneal Dialysis.

OBJECTIVE: Cognition of peritoneal dialysis patients is influenced by various factors including dialysis adequacy such as fractional urea clearance (Kt/V) and relative overhydration (RelOH). This study aimed to discover the potential contribution of dialysis adequacy to cognitive function in patients undergoing peritoneal dialysis. METHODS: Fifty-nine patients undergoing peritoneal dialysis were recruited. Demographic information, comorbidities, and clinical lab findings were retrospectively collected, and dialysis adequacy was determined by the Kt/V and RelOH calculation. Cognition and depression were measured with Digit Symbol Substitution Test, Hopkins Verbal Learning Test, Wechsler memory scale (spatial span), Wisconsin Card Sorting Test, and Beck's depression inventory. Partial correlation test was used to explore the correlation of dialysis adequacy with cognitive function. RESULTS: RelOH showed significant correlation with some of the Wisconsin Card Sorting test results. The categories achieved showed negative correlation (r=-0.32, p=0.02) and trials to complete first category showed positive correlation (r=0.31, p=0.02) with RelOH. Other tasks showed no significant correlation with RelOH. Kt/V. CONCLUSION: Our study demonstrates that peritoneal dialysis adequacy, measured by RelOH, seems to be significantly correlated with the occurrence of cognitive impairment. The outcome suggests that RelOH may have the potential to clarify the role of cognitive impairment in peritoneal dialysis patients.

Role of Prior Split Renal Function for Living Kidney Transplantation in Recipients and Donors.

PURPOSE: The purpose of this study was to determine the relationship between pre-operative donor split renal function (SRF) and the renal function outcome of donors and recipients after kidney transplantation (KT). METHODS: A total of 217 living KT cases were investigated. The estimated glomerular filtration rate (eGFR) change of recipients and donors, as well as graft survival, were analyzed based on the donor SRF. The difference in SRF (dSRF) in a donor was defined as follows: the SRF of the donated kidney minus the SRF of the remaining kidney determined by pre-operative 99mTc-diethylenetriaminepentaacetic acid in the donors. The dSRF was categorized into tertiles. RESULTS: The dSRF was not associated with the eGFR in recipients in any tertile at 6 or 12 months post-KT. The overall graft and patient survival did not differ significantly among tertiles. Donors in the high tertile, who donated kidneys with a higher SRF, showed a greater reduction in eGFR than did donors in the low and middle tertile after adjustment for function of the not-donated kidney (-34 ± 1.9 vs -28 ± 2.2, and -27 ± 1.3 mL/min/1.73 m2, P < .05). CONCLUSIONS: The dSRF did not affect the post-KT renal function or graft survival in recipients. However, the donors who donated the better functioning kidney had a poorer renal function after donation.

Effects of mealworm (Tenebrio molitor) larvae hydrolysate on nutrient ileal digestibility in growing pigs compared to those of defatted mealworm larvae meal, fermented poultry by-product, and hydrolyzed fish soluble.

OBJECTIVE: To investigate effect of mealworm (Tenebrio molitor) larvae hydrolysate on nutrient ileal digestibility compared to those of dried mealworm larvae meal, fermented poultry by-product, and hydrolyzed fish soluble in growing pigs. METHODS: A total of 12 crossbred ([Landrace×Yorkshire]×Duroc) growing pigs with average body weight of 28.70±0.32 kg were surgically equipped with simple T-cannulas. A total of 12 pigs were assigned to individual metabolic crates and allotted to one of four treatments with 3 replicates in a fully randomized design. RESULTS: Apparent ileal digestibility (AID) of dry matter (DM) was the highest in pigs fed HML diet. AIDs of crude protein (CP) were higher in pigs fed HML and DMLM diets than those in pigs fed the other two diets. AID of total amino acid was higher (p = 0.06) in pigs fed HML diet. AIDs of lysine (Lys), methionine (Met), and threonine (Thr) were similar in pigs fed DMLM and HML diets, but were higher (p = 0.05, p<0.05, and p = 0.05, respectively) than those in pigs fed FPBM or HFS diet. Pigs fed HML diet had higher standardized ileal digestibilities (SIDs) of DM and CP (p<0.05 and p<0.05, respectively) compared to pigs fed the other FPBM and HFS diets. SIDs of total amino acid were not different (p = 0.06) between treatments. For SIDs of Lys, Met, and Thr, pigs fed HML and DMLM diets showed higher SIDs (p = 0.05, p<0.05, and p<0.05, respectively) than pigs fed FPBM and HFS diets. SIDs of non-essential amino acids (aspartic acid, glycine, and alanine) were higher (p<0.05, p< 0.05, and p<0.05, respectively) in pigs fed HML, FPBM, and DMLM diets than those in pigs fed the HFS diet. AID and SID of glutamic acid were higher in pigs fed HML and FPBM diets. CONCLUSION: In conclusion, dietary supplementation of mealworm larvae hydrolysate had higher digestibility in DM, CP, Lys, Met, and Thr compared to dietary supplementation with fermented poultry by-product and hydrolyzed fish soluble.

Rapid Intestinal Uptake and Targeted Delivery to the Liver Endothelium Using Orally Administered Silver Sulfide Quantum Dots.

Quantum dots (QDs) are used for imaging and transport of therapeutics. Here we demonstrate rapid absorption across the small intestine and targeted delivery of QDs with bound materials to the liver sinusoidal endothelial cells (LSECs) or hepatocytes in vitro and in vivo following oral administration. QDs were radiolabeled with 3H-oleic acid, with a fluorescent tag or 14C-metformin placed within a drug binding site. Three different biopolymer shell coatings were compared (formaldehyde-treated serum albumin (FSA), gelatin, heparin). Passage across the small intestine into mesenteric veins is mediated by clathrin endocytosis and micropinocytosis. 60% of an oral dose of QDs was rapidly distributed to the liver within 30 min, and this increased to 85% with FSA biopolymer coating. Uptake into LSECs also increased 3-fold with FSA coating, while uptake into hepatocytes was increased from 40% to 85% with gelatin biopolymer coating. Localization of QDs to LSECs was confirmed with immunofluorescence and transmission electron microscopy. 85% of QDs were cleared within 24 h of administration. The bioavailability of 14C-metformin 2 h post-ingestion was increased 5-fold by conjugation with QD-FSA, while uptake of metformin into LSECs was improved 50-fold by using these QDs. Endocytosis of QDs by SK-Hep1 cells (an LSEC immortal cell line) was via clathrin- and caveolae-mediated pathways with QDs taken up into lysosomes. In conclusion, we have shown high specificity targeting of the LSEC or hepatocytes after oral administration of QDs coated with a biopolymer layer of FSA or gelatin, which improved the bioavailability and delivery of metformin to LSECs.