The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

Cs-RHO Goes from Worst to Best as Water Enhances Equilibrium CO2 Adsorption via Phase Change.

The strong affinity of water to zeolite adsorbents has made adsorption of CO2 from humid gas mixtures such as flue gas nearly impossible under equilibrated conditions. Here, in this manuscript, we describe a unique cooperative adsorption mechanism between H2O and Cs+ cations on Cs-RHO zeolite, which actually facilitates the equilibrium adsorption of CO2 under humid conditions. Our data demonstrate that, at a relative humidity of 5%, Cs-RHO adsorbs 3-fold higher amounts of CO2 relative to dry conditions, at a temperature of 30 °C and CO2 pressure of 1 bar. A comparative investigation of univalent cation-exchanged RHO zeolites with H+, Li+, Na+, K+, Rb+, and Cs+ shows an increase of equilibrium CO2 adsorption under humid versus dry conditions to be unique to Cs-RHO. In situ powder X-ray diffraction indicates the appearance of a new phase with Im3̅m symmetry after H2O saturation of Cs-RHO. A mixed-cation exchanged NaCs-RHO exhibits similar phase transitions after humid CO2 adsorption; however, we found no evidence of cooperativity between Cs+ and Na+ cations in adsorption, in single-component H2O and CO2 adsorption. We hypothesize based on previous Rietveld refinements of CO2 adsorption in Cs-RHO zeolite that the observed phase change is related to solvation of extra-framework Cs+ cations by H2O. In the case of Cs-RHO, molecular modeling results suggest that hydration of these cations favors their migration from an original D8R position to S8R sites. We posit that this movement enables a trapdoor mechanism by which CO2 can interact with Cs+ at S8R sites to access the α-cage.

Ovule Development and in Planta Transformation of Paphiopedilum Maudiae by Agrobacterium-Mediated Ovary-Injection.

In this paper, the development of the Paphiopedilum Maudiae embryo sac at different developmental stages after pollination was assessed by confocal laser scanning microscopy. The mature seeds of P. Maudiae consisted of an exopleura and a spherical embryo, but without an endosperm, while the inner integument cells were absorbed by the developing embryo. The P. Maudiae embryo sac exhibited an Allium type of development. The time taken for the embryo to develop to a mature sac was 45-50 days after pollination (DAP) and most mature embryo sacs had completed fertilization and formed zygotes by about 50-54 DAP. In planta transformation was achieved by injection of the ovaries by Agrobacterium, resulting in 38 protocorms or seedlings after several rounds of hygromycin selection, corresponding to 2, 7, 5, 1, 3, 4, 9, and 7 plantlets from Agrobacterium-mediated ovary-injection at 30, 35, 42, 43, 45, 48, 50, and 53 DAP, respectively. Transformation efficiency was highest at 50 DAP (2.54%), followed by 2.48% at 53 DAP and 2.45% at 48 DAP. Four randomly selected hygromycin-resistant plants were GUS-positive after PCR analysis. Semi-quantitative PCR and quantitative real-time PCR analysis revealed the expression of the hpt gene in the leaves of eight hygromycin-resistant seedlings following Agrobacterium-mediated ovary-injection at 30, 35, 42, 43, 45, 48, 50, and 53 DAP, while hpt expression was not detected in the control. The best time to inject P. Maudiae ovaries in planta with Agrobacterium is 48-53 DAP, which corresponds to the period of fertilization. This protocol represents the first genetic transformation protocol for any Paphiopedilum species and will allow for expanded molecular breeding programs to introduce useful and interesting genes that can expand its ornamental and horticulturally important characteristics.

Impact of the use of anti-diabetic drugs on survival of diabetic dialysis patients: a 5-year retrospective cohort study in Taiwan.

BACKGROUND: Type 2 diabetes mellitus (DM) and associated complications are common in patients with chronic kidney disease (CKD) and can increase morbidity and mortality. A longitudinal 5-year observational study was conducted to investigate whether the use of anti-diabetic medications or not affected survival rates of diabetic dialysis patients. METHODS: Using a data sample of a million patients from Taiwan's National Health Insurance Database, a retrospective cohort study surveyed patients with type 2 DM who began dialysis between 2002 and 2007. The study population was classified into groups using or not using anti-diabetic drugs. The group using anti-diabetic drugs was then categorized into 3 subgroups, including use of only oral hypoglycemic agents (OHAs), only insulin, and OHAs-combined insulin groups. Subjects of these four groups were followed 5 years or to date of death. Three major areas were analyzed: (1) demographic data and medical history; (2) survival prognosis and causes of death; and (3) effects on survival prognosis of different classes of OHAs. RESULTS: A total of 912 patients fitting inclusion criteria were enrolled and followed-up for 5 years or to date of death. A total 465 patients died, and those not using anti-diabetic drugs (67.34 %) had a higher mortality rate than those using anti-diabetic drugs (46.42 %). After the multivariate analysis, group of OHAs-combined insulin had the lowest risk of death (HR 0.36, 95 % CI 0.27-0.47), followed by OHAs alone (HR 0.49, 95 % CI 0.38-0.63) and then insulin alone (HR 0.67, 95 % CI 0.51-0.88). To clarify four classes of OHAs (sulfonylurea, α-glucosidase inhibitors, meglitinide, and thiazolidinedione) are used in Taiwan for uremia patient with type 2 DM, and in our study, there were no significant differences in survival prognosis for the four drugs. Finally, the most common cause of death was infectious disease and there were no significant differences among the four groups. CONCLUSION: This 5-year observational study results suggested that diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs. Despite insulin therapy, appropriate OHAs should play an important role in treating these patients.

Comparison of short-term efficacy of iron sucrose with those of ferric chloride in hemodialysis patients: An open-label study.

BACKGROUND: It is intriguing and imperative that the comparison of the iron preparations in hemodialysis (HD) patients. This study aimed to observe the short-term efficacy of parenteral iron sucrose and ferric chloride in HD patients. MATERIALS AND METHODS: This was a consecutive 10-week single-blind study in Taiwan. An intravenous iron supplement of 100 mg/week was administered as an infusion in 100 ml of normal saline, until a total dose of 1000 mg was achieved. The primary outcome was evaluated by the changes in serum hematocrit (Hct) levels. The changes in serum Hct and iron indices were evaluated every 2 weeks for 10 weeks. The results were collected from 21 April to 4 July 2013. RESULTS: A total of 56 HD patients completed the study. Subjects were randomized into an iron sucrose group (26 patients) and a ferric chloride group (30 patients). Between the two treatment groups, there were no statistically significant differences in the change in serum Hct, ferritin, iron, or total iron binding capacity (P > 0.05). In the iron sucrose group, the increase in Hct levels was statistically significant at weeks 4, 8, and 10. In the ferric chloride group, the increase in Hct levels was statistically significant at week 8. No obvious major side effects were observed in both groups. CONCLUSION: In the study subjects, parenteral iron sucrose was as effective and safe as ferric chloride for treating anemia in HD patients.

Developing a Motion Sensor-Based Game to Support Frozen Shoulder Rehabilitation in Older Adults through a Participatory Design Approach.

Objective: Although some serious games have been developed for physical therapy, little work has been conducted through a participatory design approach. Therefore, a game prototype was developed, which involved related stakeholders in the design process. Materials and Methods: The iterative participatory design process was adopted with the input of 18 patients with frozen shoulder symptoms, 4 health professionals, 2 game designers, and 5 researchers in an iterative process to design, test, and evaluate the game prototype. In total, 17 patients participated in the interviews to explore their needs and desires for a serious game. The health professionals participated in the interviews to understand the medical requirement and experience pertaining to frozen shoulder and were included in the workshop to give feedback on the game prototype. At the conclusion of the iterative design process, a Kinect-based prototype game with three levels was used for a case study with one patient who was diagnosed with frozen shoulder and has been receiving medical treatment in the hospital. Results: Based on the outcomes derived from data collected among diverse stakeholders, the prototype game underwent iterative development by the team and was assessed by a participant with frozen shoulder symptoms. Findings revealed that the participant demonstrated enhanced shoulder mobility and a reduction in pain intensity, despite the lack of significant improvement for health-related quality of life. Nevertheless, the participant reported a positive experience with the prototype game. Conclusion: This study underscores the importance of involving diverse stakeholders in the development process to create more effective and user-centric serious games for rehabilitation. The participatory approach, exemplified by the prototype game, demonstrates potential improvements in both user experience and overall effectiveness during the rehabilitation process.

Biomedical Evaluation of Early Chronic Kidney Disease in the Air Force: Building a Predictive Model from the Taiwan Military Health Service.

OBJECTIVE: Chronic kidney disease (CKD) is one of the most common diseases worldwide. The increasing prevalence and incidence of CKD have contributed to the critical problem of high medical costs. Due to stressful environments, aircrew members may have a high risk of renal dysfunction. A better strategy to prevent CKD progression in Air Force personnel would be to diagnosis CKD at an early stage. Since few studies have been conducted in Taiwan to examine the long-term trends in early CKD in Air Force aircrew members, this study is highly important. We investigated the prevalence of CKD and established a predictive model of disease variation among aircrew members. MATERIALS AND METHODS: In this retrospective study, we included all subjects who had received physical examinations at a military hospital from 2004 to 2010 and who could be tracked for four years. The Abbreviated Modification of Diet in Renal Disease Formula (aMDRD) was used to estimate the glomerular filtration rate (GFR) and was combined with the National Kidney Foundation/ Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) to identify CKD patients. RESULTS: A total of 212 aircrew members were assessed. The results showed that the prevalence of CKD was 3.8%, 9.4%, 9.0%, and 9.4% in each of the four years. According to the logistic regression analysis, abnormal urobilinogen levels, ketones, and white blood cell (WBC) counts in urine and a positive urine occult blood test increased the risk of CKD. A positive urine occult blood test can be used to predict the future risk of CKD. Moreover, the generalized estimating equation (GEE) model showed that a greater risk of CKD with increased examination time, age and seniority had a negative effect. In conclusion, abnormal urobilinogen levels, ketones, and urine WBC counts in urine as well as a positive urine occult blood test might serve as independent predictors for CKD. CONCLUSION: In the future, we can focus not only on annual physical examinations but also on simple and accurate examinations, such as urine occult blood testing, to determine the risk of CKD and prevent its progression in our aircrew members.

Dispersion mapping at the micrometer scale using tri-band optical frequency domain imaging.

Techniques to differentiate between materials are a powerful addition to the structural information traditionally available from optical coherence tomography images. We present label-free detection of water and lipid at a micrometer scale by evaluating their unique dispersion properties. Using a tri-band swept source configuration, we measure both ß(2) and ß(3) and show how to identify the two materials at sample thicknesses of 40 and 90 µm, respectively.

Pharmacological regulation of protein-polymer hydrogel stiffness.

The extracellular matrix (ECM) undergoes constant physiochemical change. User-programmable biomaterials afford exciting opportunities to study such dynamic processes in vitro. Herein, we introduce a protein-polymer hydrogel whose stiffness can be pharmacologically and reversibly regulated with conventional antibiotics. Specifically, a coumermycin-mediated homodimerization of gel-tethered DNA gyrase subunit B (GyrB) creates physical crosslinking and a rheological increase in hydrogel mechanics, while competitive displacement of coumermycin with novobiocin returns the material to its softened state. These unique platforms could potentially be modulated in vivo and are expected to prove useful in elucidating the effects of ECM-presented mechanical signals on cell function.

FTO-mediated epigenetic upregulation of LINC01559 confers cell resistance to docetaxel in breast carcinoma by suppressing miR-1343-3p.

This study was to explore the regulatory effect of long non-coding RNA LINC01559 on Docetaxel resistance in breast carcinoma (BCa) and its underlying mechanism. In the present study, we found that LINC01559 expression was elevated and LINC01559 overexpression facilitated docetaxel resistance in BCa cells. Moreover, it was revealed that the upregulation of LINC01559 in BCa cells was induced by FTO-mediated demethylation in an m6A-YTHDF2-dependent manner. Additionally, Dual-luciferase reporter assay confirmed the binding ability between LINC01559 and miR-1343-3p, and Pearson correlation analysis showed a negative correlation between them. Particularly, miR-1343-3p inhibition partly abolished the suppression on docetaxel resistance in BCa cells caused by LINC01559 knockdown. To sum up, FTO-mediated epigenetic upregulation of LINC01559 promoted cell resistance to Docetaxel in BCa by negatively regulating miR-1343-3p.

MicroRNA regulators of vascular pathophysiology in chronic kidney disease.

Coronary artery disease (CAD) is a severe comorbidity in chronic kidney disease (CKD) due to heavy calcification in the medial layer and inflamed plaques. Chronic inflammation, endothelial dysfunction and vascular calcification are major contributors that lead to artherosclerosis in CKD. The lack of specific symptoms and signs of CAD and decreased accuracy of noninvasive diagnostic tools result in delayed diagnosis leading to increased mortality. MicroRNAs (miRNAs) are post-transcriptional regulators present in various biofluids throughout the body. In the circulation, miRNAs have been reported to be encapsulated in extracellular vesicles and serve as stable messengers for crosstalk among cells. miRNAs are involved in pathophysiologic mechanisms including CAD and can potentially be extended from basic research to clinical translational practice.

Association of Dietary Fish and n-3 Unsaturated Fatty Acid Consumption with Diabetic Nephropathy from a District Hospital in Northern Taiwan.

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin-creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781-0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688-0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823-0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.

The complete chloroplast genome of Stichorkis gibbosa (Orchidaceae: Malaxideae).

Stichorkis gibbosa is a rare orchid species of the tribe Malaxideae mainly distributed in tropical Asia. This is the only species of the genus Stichorkis Thouars which has been reported to occur in China. Despite the importance of this genus, previous molecular studies based on few markers have resulted in limited phylogenetic resolution. With the decline of habitats, the wild population of S. gibbosa has decreased in recent years. In this study, we first reported the complete chloroplast (cp) genome of S. gibbosa. The entire cp genome was determined to be 158,056 bp in length with overall GC content of 36.9%, containing a pair of inverted repeat regions (IRs) of 27,006 bp, separated by a large single-copy (LSC, 86,280 bp) and a small single-copy (SSC, 17,764 bp). A total of 133 unique genes were annotated, including 87 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The phylogenetic tree indicated that S. gibbosa was a sister group of the genus Oberonia and the epiphytic Liparis alliance with strong support.

Investigation of the Relationship between Lean Muscle Mass and Erythropoietin Resistance in Maintenance Haemodialysis Patients: A Cross-Sectional Study.

Each patient undergoing maintenance haemodialysis (MHD) has a different response to erythropoiesis-stimulating agents (ESAs). Haemodilution due to fluid overload has been shown to contribute to anaemia. Body mass index (BMI) has been shown to influence ESA response in dialysis patients; however, BMI calculation does not distinguish between fat and lean tissue. The association between lean muscle mass and erythropoietin hyporesponsiveness is still not well-known among MHD patients. We designed a cross-sectional study and used bioimpedance spectroscopy (BIS) to analyse the relationship between body composition, haemoglobin level, and erythropoietin resistance index (ERI) in MHD patients. Seventy-seven patients were enrolled in the study group. Compared with patients with haemoglobin ≥ 10 g/dL, those with haemoglobin < 10 g/dL had higher serum ferritin levels, malnutrition−inflammation scores (MIS), relative overhydration, ESA doses, and ERIs. In multivariate logistic regression, higher ferritin levels and MIS were the only predictors of lower haemoglobin levels. The ERI was significantly positively correlated with age, Kt/V, ferritin levels, and MIS and negatively correlated with albumin levels, BMI, and lean tissue index (LTI). Multivariate linear regression analysis revealed that ferritin levels, BMI, and LTI were the most important predictors of ERI. In MHD patients, using BIS to measure body composition can facilitate the development of early interventions that aim to prevent sarcopenia, support ESA responsiveness, and, consequently, improve anaemia management.

The role of anti-platelet factor 4 antibodies and platelet activation tests in patients with vaccine-induced immune thrombotic thrombocytopenia: Brief report on a comparison of the laboratory diagnosis and literature review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human pathogen causing coronavirus disease 2019 (COVID-19). Rare cases of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) after the ChAdOx1 nCoV-19 (AstraZeneca) vaccination have been reported. We performed a test for anti-heparin/ platelet factor 4 (PF4) antibodies and functional assay using flow cytometry. METHOD: A healthy woman presented to the emergency department with chest pain, headache, and abdominal pain after the first vaccination with AstraZeneca. Polymerase chain reaction (PCR) test for SARS-CoV-2 was negative. Chest computed tomography (CT) showed pulmonary artery embolism and brain magnetic resonance imaging (MRI) revealed cerebral sinus-venous thrombosis. Abdominal CT demonstrated the thrombosis with occlusion in her right hepatic vein. Laboratory studies revealed decreased platelet counts, and high D-dimer level. Finally, laboratory results indicated high PF4 antibodies level high and a positive platelet activation test, confirming the diagnosis of VITT. RESULTS: Treatments including intravenous immunoglobulin, methylprednisolone and direct oral anticoagulant were administered. The results of a follow-up platelet count and D-dimer were normal. In addition, the titer of PF4 antibodies (optical density: 0.425; normal ≤ 0.4, enzyme-linked immunosorbent assay) fell. After a 3-month follow-up, her general condition improved gradually. CONCLUSIONS: The use of COVID-19 vaccines to prevent SARS-CoV-2 infections and complications is considered the most practicable policy for controlling the COVID-19 pandemic and is being forcefully pursued in the global area. Appropriate laboratory diagnosis facilitates the accurate and rapid diagnosis. Early recognizing and appropriate strategies for VITT are required and can provide these patients with more favorable patient outcomes. This report also elected to make comparisons of clinical manifestation, laboratory diagnosis, and management in patients with VITT.

From Bench to Bedside: Clinical and Biomedical Investigations on Hepatitis C Virus (HCV) Genotypes and Risk Factors for Albuminuria.

An extrahepatic manifestation of nephropathies can be a feature of the chronic hepatitis C virus (HCV) infection. Albuminuria is a major risk factor for nephropathies and chronic kidney disease (CKD). The correlation between HCV genotypes and albuminuria is still unclear. In this study, investigations have been done for the biomedical tools and methodologies used in the National Health and Nutrition Examination Survey (NHANES) public database. We searched the 2007−2016 NHANES public database to retrieve data regarding the different HCV genotypes and clinical scenarios. This study attempted to investigate the impacts of HCV genetic diversity, associated comorbidities, and racial differences on albuminuria. The urine albumin/creatinine ratio (ACR) was the primary endpoint. Among 40,856 participants, 336 participants with positive and 237 with negative HCV RNA tests were analyzed, excluding 14,454 participants with negative HCV antibodies and 25,828 which were missed. After controlling for sex, race, education level, smoking, diabetes mellitus, hepatitis B, alcohol use, and body mass index (BMI) with a generalized linear equation, HCV genotype 2 was more likely than any other genotype to cause albuminuria based on the urine ACR (p < 0.001). The generalized linear equation also demonstrated a significantly higher urine ACR, including hepatitis B (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.026). In summary, the patients with HCV genotype 2 presented with increased albuminuria in comparison with other HCV genotypes in this 10-year retrospective analysis. HCV infection could be a risk factor of CKD; early diagnosis and appropriate treatment may improve clinical outcomes.

Peritoneal effluent MicroRNA profile for detection of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS. METHODS: We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning. RESULTS: Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-ß signaling pathway. CONCLUSION: The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS.

Hypokalemic paralysis in hyperthyroidism: Not all that glitter are gold.

Abnormal acid-base status (metabolic acidosis or alkalosis), inappropriate urine electrolytes excretion (high or low Na+ and Cl-), and higher required dose of potassium supplement (4-5 mmol/kg) are suggestive of non-TPP causes of hypokalemia.

Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease.

The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines' effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD's complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.

miRNA as a Modulator of Immunotherapy and Immune Response in Melanoma.

Immune checkpoint inhibitors are a promising therapy for the treatment of cancers, including melanoma, that improved benefit clinical outcomes. However, a subset of melanoma patients do not respond or acquire resistance to immunotherapy, which limits their clinical applicability. Recent studies have explored the reasons related to the resistance of melanoma to immune checkpoint inhibitors. Of note, miRNAs are the regulators of not only cancer progression but also of the response between cancer cells and immune cells. Investigation of miRNA functions within the tumor microenvironment have suggested that miRNAs could be considered as key partners in immunotherapy. Here, we reviewed the known mechanism by which melanoma induces resistance to immunotherapy and the role of miRNAs in immune responses and the microenvironment.