Water Extract of Portulaca Oleracea Inhibits PEDV Infection-Induced Pyrolysis by Caspase-1/GSDMD.

Porcine epidemic diarrhea virus (PEDV) belongs to the coronavirus family and the coronavirus genus, causing contact enteric infection in pigs. It is one of the most serious diseases that threatens the pig industry. However, there is currently no specific drug to prevent and treat the disease, indicating that we need to be vigilant about the spread of the disease and the development of anti-PEDV drugs. The dried aerial parts of the plant Portulaca oleracea in the family Portulacaceous, whose decoction can be used to treat acute enteritis, dysentery, diarrhea, and other diseases. This study explored the potential mechanism of water extract of Portulaca oleracea (WEPO) in PEDV-induced pyroptosis in Vero cells. PEDV decreased the viability of Vero cells in a dose- and time-dependent manner, causing cell damage, upregulating the level of intracellular Nlrp3, and inhibiting the level of Gasdermin D (GSDMD) and the activation of Caspase-1. WEPO can inhibit PEDV-induced pyroptosis, reduce the elevation of inflammatory factors caused by infection, and exhibit a dose-dependent effect. Knockdown of Caspase-1 and GSDMD separately can induce the production of the inflammatory factor IL-1ß to significantly decrease and increase, respectively. These results suggest that WEPO can inhibit cell pyroptosis caused by PEDV and that the Caspase-1 and GSDMD pathways play an important role in this process.

Assessment of an exhaled breath test using ultraviolet photoionization time-of-flight mass spectrometry for the monitoring of kidney transplant recipients.

Continuous monitoring for immunosuppressive status, infection and complications are a must for kidney transplantation (KTx) recipients. Traditional monitoring including blood sampling and kidney biopsy, which caused tremendous medical cost and trauma. Therefore, a cheaper and less invasive approach was urgently needed. We thought that a breath test has the potential to become a feasible tool for KTx monitoring. A prospective-specimen collection, retrospective-blinded assessment strategy was used in this study. Exhaled breath samples from 175 KTx recipients were collected in West China Hospital and tested by online ultraviolet photoionization time-of-flight mass spectrometry (UVP-TOF-MS). The classification models based on breath test performed well in classifying normal and abnormal values of creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and tacrolimus, with AUC values of 0.889, 0.850, 0.849 and 0.889, respectively. Regression analysis also demonstrated the predictive ability of breath test for clinical creatinine, eGFR, BUN, tacrolimus level, as the predicted values obtained from the regression model correlated well with the clinical true values (p < 0.05). The findings of this investigation implied that a breath test by using UVP-TOF-MS for KTx recipient monitoring is possible and accurate, which might be useful for future clinical screenings.

Novel pyridinium cationic pleuromutilin analogues overcoming bacterial multidrug resistance.

A series of pyridinium cation-substituted pleuromutilin analogues were designed, synthesized and evaluated for their antibacterial activities in vitro and in vivo. Most derivatives showed potent antibacterial activities, especially e4 that displayed the highest antibacterial activity against multi-drug resistant bacteria and was subjected to time-kill kinetics, resistance studies, cytotoxicity and molecular docking assays. Molecular docking results, scanning electron microscopy and o-nitrophenyl-ß-galactopyranoside tests showed that e4 not only inhibited bacterial protein synthesis but also disrupted bacterial cell walls. Compound e4 showed an ED50 of 5.68 mg/kg against multi-drug resistant Staphylococcus aureus in infected mice model. In in vivo and in vitro toxicity tests, e4 showed low toxic effects with an LD50 of 879 mg/kg to mice. These results suggest that compound e4 may be considered as a new therapeutic candidate for bacterial infections.

Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent pleuromutilin derivatives with a substituted piperazine moiety.

Antibiotic-resistant bacteria pose a major global public health concern, owing to the lack of effective antibacterial drugs. Consequently, the discovery and development of innovative antibacterial drug classes with unique mechanisms of action are urgently needed. In this study, we designed, synthesised, and tested a series of novel pleuromutilin derivatives with piperazine linker substituted by amino acids moieties to determine their antibacterial properties. Most synthesized compounds exhibited potent activities against Staphylococcus aureus (S. aureus), methicillin-resistant S. aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis. Compound 6l, the most potent antibacterial agent created in this study, displayed a rapid bactericidal activity against MRSA, Klebsiella pneumoniae and S. aureus cfr N12. Moreover, pharmacokinetics study of compound 6l exhibited good PK performance with a low in vivo clearance (CL = 1965 mL/h/kg) and a suitable half-life (T1/2 = 11.614 ± 5.123 h). Molecular docking experiments revealed the binding model of compound 6l to the unmethylated A2503 of peptidyl transferase centre of 23S rRNA. Interaction pattern of 6l with cfr-mediated ribosomes revealed by molecular dynamics. Moreover in vivo mouse systemic infection experiments with compound 6l revealed its effectiveness against MRSA and S. aureus cfr N12 with the ED50 of 11.08 mg/kg and 14.63 mg/kg body weight, respectively.

Health risk assessment of mercury in Nile tilapia (Oreochromis niloticus) fed housefly maggots.

The bioaccumulation of total mercury (THg) and methylmercury (MeHg) by housefly maggots (HM) during the conversion of food waste (vegetables and meat (VM) and rice waste) under various waste feed ratios were investigated. Subsequently, Nile tilapia (Oreochromis niloticus) were fed with the commercial feed, commercial dried HM, dried HM, and fresh HM, followed by a human health risk assessment of Hg via fish consumption. The THg concentrations of HM fed with food waste ranged from 39.5 to 100 µg kg-1 ww. Concentrations of MeHg in the maggots fed with 100 % vegetables and meat (VM) waste (13.7 ± 1.12 µg kg-1 ww) was significantly higher than that fed with other mixed ratios of rice waste and VM waste (p<0.05). Concentrations of MeHg were positively correlated with the weight and lipid content of houseflies (p<0.05). THg and MeHg concentrations in tilapia fed with the converted HM (dried and fresh HM) were 22.5 ± 6.50 µg kg-1 ww and 2.43 ± 0.36 µg kg-1 ww, respectively. There was no significant difference in MeHg between tilapia fed the four experiment diets (p>0.05). Health risk assessment results indicated that mercury in tilapia fed the food waste-grown HM did not pose potential health risks to humans (target hazard quotient < 1). In conclusion, HM could convert food waste into high-quality and safe fish feeds for cultivating tilapia.

Transplant outcomes of 100 cases of living-donor ABO-incompatible kidney transplantation.

BACKGROUND: Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS: From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS: After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P  = 0.787, P  = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P  = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P  = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P  = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P  = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P  = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS: An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.

Novel gold-platinum nanoparticles serve as broad-spectrum antioxidants for attenuating ischemia reperfusion injury of the kidney.

Kidney ischemia reperfusion injury (IRI) is a common and inevitable pathological condition in routine urological practices, especially during transplantation. Severe kidney IRI may even induce systemic damage to peripheral organs, and lead to multisystem organ failure. However, no standard clinical treatment option is currently available. It has been reported that kidney IRI is predominantly associated with abnormally increased endogenous reactive oxygen species (ROS). Scavenging excessive ROS may reduce the damage caused by oxidative stress and subsequently alleviate kidney IRI. Here, we reported a simple and efficient one-step synthesis of gold-platinum nanoparticles (AuPt NPs) with a gold core having a loose and branched outer platinum shell with superior ROS scavenging capacity to possibly treat kidney IRI. These AuPt NPs exhibited multiple enzyme-like anti-oxidative properties simultaneously possessing catalase- and peroxidase-like activity. These particles showed excellent cell protective capability, and alleviated kidney IRI both in vitro and in vivo without obvious toxicity, by suppressing cell apoptosis, inflammatory cytokine release, and inflammasome formation. Meanwhile, AuPt NPs also had an effect on inhibiting the transition to chronic kidney disease by reducing kidney fibrosis in the long term. Thus, AuPt NPs might be a good therapeutic agent for kidney IRI management and may be helpful for the development of clinical treatments for kidney IRI.

ILDR1 promotes influenza A virus replication through binding to PLSCR1.

As a natural antiviral regulator, phospholipid scramblase 1 (PLSCR1) has been shown to inhibit influenza virus replication in infected cells through interacting with NP of influenza A virus (IAV). But its antiviral function as well as the underlying regulatory mechanism has not been examined in vivo. In the present work, we show that PLSCR1 expression is decreased in H1N1 SIV-infected mice, and Plscr1-/- mice are more susceptible to H1N1 SIV infection. By performing yeast two-hybrid screening, we identified immunoglobulin-like domain-containing receptor 1 (ILDR1) as a novel PLSCR1-binding partner. ILDR1 is highly expressed in the lungs, and its expression level is increased after virus infection. Interestingly, ILDR1 could not directly interact with virus NP protein, but could combine with PLSCR1 competitively. Our data indicates that there is a previously unidentified PLSCR1-ILDR1-NP regulatory pathway playing a vital role in limiting IAV infection, which provides novel insights into IAV-host interactions.

Minimally Invasive Kidney Transplantation Had Better Cosmetic Effect and Comparable Safety: A Randomized Controlled Trial.

PURPOSE: To prospectively evaluate short-term outcomes between a novel minimally invasive kidney transplantation (MIKT) technique and conventional kidney transplantation (CKT). MATERIALS AND METHODS: From March 2018 to February 29, 2019, 148 patients were randomized into MIKT and CKT groups. All patients were followed up for 12 months. RESULTS: The MIKT group had a significantly shorter incision length (5.6 ± 0.4 vs 11.4 ± 0.4 cm, P < .001). There was no difference in operation time, blood loss, acute rejection, infection, and wound dehiscence between MIKT and CKT groups. Both groups had comparable pain scores and analgesic requirements in the first 3 days after transplantation and comparable renal function at 12 months. The MIKT group had higher satisfaction than the CKT group during follow-up (9.3 ± 0.3 vs 8.1 ± 0.5, P < .001; 9.5 ± 0.2 vs 8.5 ± 0.3, P < .001; 9.4 ± 0.3 vs 8.5 ± 0.3, P < .001; 9.2 ± 0.3 vs 8.5 ± 0.4, P = .003 for posttransplant months 1, 3, 6, and 12, respectively). The MIKT group had a significantly lower Vancouver Scar Scale score (4.1 ± 0.4 vs 5.2 ± 0.5, P < .001; 4.3 ± 0.4 vs 6.1 ± 0.4, P < .001; 5.2 ± 0.6 vs 6.7 ± 0.5, P < .001; 7.7 ± 0.7 vs 8.9 ± 0.5, P = .009 for posttransplant months 1, 3, 6, and 12, respectively). CONCLUSIONS: MIKT has demonstrated equivalent safety and improved patient satisfaction compared to CKT. This technique may be an appropriate choice for selected patients.

Prevalence of vitamin D deficiency and impact on clinical outcomes after kidney transplantation: a systematic review and meta-analysis.

CONTEXT: The prevalence of vitamin D deficiency (VDD) and its impact on clinical outcomes after kidney transplant (KT) remain poorly defined. OBJECTIVES: We conducted a meta-analysis to evaluate the impact of early VDD on clinical outcomes after KT. DATA SOURCES: Electronic databases (PubMed, Embase, Web of Science, and The Cochrane Library) were systematically searched for eligible publications up to April 30, 2020. DATA EXTRACTION: Relative risk was presented as hazard ratios (HRs) or odds ratios (ORs) and 95%CIs for dichotomous outcomes. Mean difference (MD) and 95%CIs were presented for continuous outcomes. RESULTS: A total of 28 studies (13 prospective and 15 retrospective) were included. VDD was common early after KT, with a prevalence of 52% (95%CI: 41%-64%) at transplant, 34% (95%CI: 17%-51%) at 3 months, and 23% (95%CI: 10%-35%) at 6 months. Early VDD was associated with higher mortality rate after KT (HR, 1.56; 95%CI: 1.32-1.84; P < 0.001). In addition, early VDD led to higher risk of bacterial infection (OR, 1.82; 95%CI: 1.40-2.36; P < 0.001), BK polyomavirus infection (OR, 2.11, 95%CI: 1.23-3.61; P = 0.006), and cytomegalovirus infection (OR, 1.69; 95%CI: 1.24-2.31; P = 0.001). Early VDD increased the risk of acute rejection as well (HR, 2.28; 95%CI: 1.57-3.30; P < 0.001). Recipients with early VDD had lower estimated glomerular filtration rates (mean difference: -5.06; 95%CI: -7.28 to 2.83 mL/min; P < 0.001). Sensitivity analyses showed good stability of the pooled results. CONCLUSION: VDD was common early after KT and associated with higher risk of death and adverse outcomes.

Tacrolimus variability score outperforms coefficient of variation in predicting clinical outcomes of living kidney transplantation.

AIMS: Intrapatient variability (IPV) was previously defined as coefficient of variation (CV) or standard deviation of tacrolimus (Tac) exposure while none of them was easily being interpreted and translated into clinical practice after kidney transplantation. METHODS: We developed a novel Tac variability score (TVS) to evaluate IPV by calculating the frequency of clinically significant changes of Tac trough levels after kidney transplantation. Multivariate Cox proportional analyses were conducted to compare the impact of TVS and CV on transplant outcomes. RESULTS: A total of 1343 patients were divided into high TVS (>0.30) and low TVS (<0.30) groups, and low CV (<0.30) and high CV (>0.30) groups. Univariate analyses showed that high TVS (hazard ratio [HR]: 2.323, 95% confidence interval [CI]: 1.455-3.709) and high CV (HR: 1.606, 95%CI: 1.044-2.471) were associated with inferior graft survival. However, only TVS was an independent predictor for graft failure in multivariate analyses (HR: 1.972, 95%CI: 1.2-3.24), and the correlation maintained in high CV (P = .020) and low CV (P = .037) subgroups, while CV failed to predict graft loss in neither low (P = .387) nor high TVS (P = .600) subgroups. In addition, TVS had a higher correlation with graft survival in patients with Tac exposure within the therapeutic range and the correlation was less influenced by mean Tac trough levels. CONCLUSION: TVS is a novel measure of Tac IPV with higher correlation with graft survival and more convenience in clinical use than CV after kidney transplantation.

Nonlinear relationship between body mass index and clinical outcomes after kidney transplantation: A dose-response meta-analysis of 50 observational studies.

BACKGROUND: Exact dose-response relationship between body mass index at transplantation and clinical outcomes after kidney transplantation remained unclear, and no specific body mass index threshold and pretransplant weight loss aim were recommended for kidney transplantation candidates among transplant centers. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for literature published up to December 31, 2019. The two-stage, random effect meta-analysis was performed to estimate the dose-response relationship between body mass index and clinical outcomes after kidney transplantation. RESULTS: Ninety-four studies were included for qualitative assessment and 50 for dose-response meta-analyses. There was a U-shaped relationship between graft loss, patient death, and body mass index. Body mass index with the lowest risk of graft loss was 25.2 kg/m2, and preferred body mass index range was 22-28 kg/m2. Referring to a body mass index of 22 kg/m2, the risk of graft loss was 1.088, 0.981, 1.003, and 1.685 for a body mass index of 18, 24, 28, and 40 kg/m2, respectively. Body mass index with the lowest risk of patient death was 24.7 kg/m2, and preferred body mass index range was 22-27 kg/m2. Referring to a body mass index of 22 kg/m2, the patient death risk was 1.115, 0.981, 1.032, and 2.634 for a body mass index of 18, 24, 28, and 40 kg/m2, respectively. J-shaped relationships were observed between body mass index and acute rejection, delayed graft function, primary graft nonfunction, and de novo diabetes. Pair-wise comparisons showed that higher body mass index was also a risk factor for cardiovascular diseases, hypertension, infection, longer length of hospital stay, and lower estimated glomerular filtration rate level. CONCLUSION: Underweight and severe obesity at transplantation are associated with a significantly increased risk of graft loss and patient death. A target body mass index at kidney transplantation is 22-27 kg/m2.

miR-17-5p attenuates kidney ischemia-reperfusion injury by inhibiting the PTEN and BIM pathways.

BACKGROUND: Kidney ischemia-reperfusion (I/R) injury is an independent risk factor for delayed graft function after kidney transplantation with long-term graft survival deterioration. Previously, we found that the upregulated expression of miR-17-5p exerts a protective effect in kidney I/R injury, but the mechanism has not been clearly studied. METHODS: A kidney I/R injury model was induced in adult C57BL/6 male mice (20-22 g) by clamping both kidney pedicles for 30 min. The miR-17-5p agomir complex was injected into mice 24 h before surgery via the tail vein at a total injection volume of 10 µL/g body weight. The mice were euthanized on post-I/R injury day 2, and kidney function, apoptosis, autophagy, and related molecules were then detected. Human kidney-2 (HK-2) cells, which underwent hypoxia/reoxygenation, were treated with the miR-17-5p agomir, miR-17-5p antagomir, and small interfering ribonucleic acids (siRNAs). Cell viability, apoptosis, autophagy, and molecules were also examined. RESULTS: Autophagy, miR-17-5p expression, and kidney function damage were significantly more increased in the I/R group than in the sham group. In the cultured HK-2 cells underwent hypoxia/reoxygenation, the miR-17-5p agomir directly inhibited the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Bcl-2 like protein 11 (BIM), and attenuated apoptosis and autophagy. Further, miR-17-5p inhibited autophagy by activating the protein kinase B (Akt)/Beclin1 pathway, which was suppressed by siRNAs. Additionally, the administration of miR-17-5p agomir greatly improved kidney function in the I/R mice group by inhibiting autophagy and apoptosis. CONCLUSIONS: These findings suggest a new possible therapeutic strategy for the prevention and treatment of kidney I/R injury. The upregulation of miR-17-5p expression appears to inhibit apoptosis and autophagy by suppressing PTEN and BIM expression, which in turn upregulates downstream Akt/Beclin1 expression.

Early Monitoring and Subsequent Gain of Tacrolimus Time-In-Therapeutic Range May Improve Clinical Outcomes After Living Kidney Transplantation.

BACKGROUND: The early identification of recipients at high risk of graft loss is clinically relevant after kidney transplantation. The authors explored whether the earlier monitoring of tacrolimus (Tac) time-in-therapeutic range (TTR) is predictive of and a subsequent gain in TTR improves transplant outcomes. METHODS: The TTR within 3, 6, 9, and 12 months was evaluated. Multivariate Cox analyses were performed to explore when TTR was predictive of transplant outcomes. Patients were divided into 3 groups based on incremental TTR change [TTR gain (increase >10%), TTR stable (maintained within 10%), and TTR loss (decrease >10%)] and 4 groups based on predefined cutoff values [low-low (LL), low-high (LH), high-low (HL), and high-high (HH)] using 6- and 12-month TTRs. Death-censored graft loss and patient death were primary outcomes. RESULTS: Nonlinear associations were observed between 6-, 9-, and 12-month TTR and death-censored graft and patient survival rates. In multivariate analysis, every 10% increase in 6-, 9-, and 12-month TTRs was associated with reduced patient death [hazard ratio (HR): 0.83; HR: 0.68; HR: 0.61, respectively] and graft loss (HR: 0.88; HR: 0.73; HR: 0.66, respectively). A nonlinear relationship was observed between transplant outcomes and incremental changes in TTR. TTR gain and stable TTR contributed to higher graft survival (HR: 0.20; HR: 0.21) and patient survival (HR: 0.14; HR: 0.15) rates than TTR loss, whereas the former 2 had comparable outcomes. Furthermore, compared with those in the HH group, the LL and HL groups had inferior graft survival (HR: 3.33; HR: 5.17) and patient survival (HR: 5.15; HR: 8.94) rates, whereas the LH group had similar outcomes (P = 0.63, P = 0.97). Nonadherence was the main controllable risk factor for low TTR. CONCLUSIONS: The 6-month TTR identified patients at higher risk of worse outcomes. The subsequent gain of TTR may contribute to better transplant outcomes.

Highly individual- and tissue-specific expression of glycoprotein group A and B blood antigens in the human kidney and liver.

BACKGROUND: Currently, research on the quantitative distribution of ABO antigens in different organs and tissues remains limited. We aimed to examine the individual characteristics of blood group glycoprotein A and B antigen expression in human kidneys and livers. METHODS: We obtained human samples, including the renal artery, renal vein, renal tissue, hepatic artery, hepatic vein, portal vein, and hepatic tissue, from 24 deceased organ transplant donors. The expression of the blood group antigens glycoprotein A and B was analysed and compared by Western blotting. RESULTS: There was no significant difference in the expression between blood group glycoprotein A and B antigens at any of the seven sites (p > 0.05). The expression of both A and B antigens was highest in renal tissue and the portal vein and was lowest in the renal artery. A large difference in glycoprotein antigen expression was observed among various donors or different regions of the same individual. Univariate analysis revealed that glycoprotein A/B antigens were affected by the age and sex of donors and were significantly higher in males and in young people. CONCLUSIONS: Our study found that blood group glycoprotein antigen expression showed certain trends and distinct distribution in the kidney, liver, and vessels among individuals and in different regions of the same individual, which may explain the different clinical outcomes of patients who received ABO-incompatible transplantation.

Conversion From Calcineurin Inhibitors to Mammalian Target of Rapamycin Inhibitors in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: A systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs). Methods: MEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy. Results: Twenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10-0.31; P<0.01) and malignancy (RR 0.74; 95%CI 0.55-0.99; P=0.04) demonstrated a significant advantage of mTORi conversion over CNI continuation. However, the risk of acute rejection (RR 1.58; 95%CI 1.22-2.04; P<0.01), infection (RR 1.55; 95%CI 1.01-1.31; P=0.04), proteinuria (RR 1.87; 95%CI 1.34-2.59; P<0.01), leukopenia (RR 1.56; 95%CI 1.27-1.91; P<0.01), acne (RR 6.43; 95%CI 3.43-12.04; P<0.01), and mouth ulcer (RR 11.70; 95%CI 6.18-22.17; P<0.01) were higher in the mTORi group. More patients in the conversion group had to discontinue study medication (RR 2.52; 95%CI 1.75-3.63; P<0.01). There was no significant difference between the two groups with regard to death, graft loss, diabetes, chronic allograft nephropathy, and interstitial fibrosis/tubular atrophy. Conclusions: Posttransplant patients have a better graft function and lower incidence of malignancy after conversion from CNI to mTORi therapy. However, this conversion strategy may be prevented by the higher drug discontinuation rate due to mTORi-associated adverse events, such as more acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, indicating that conversion therapy may only be a treatment option in selected patients.

Tea Polyphenols Enhanced the Antioxidant Capacity and Induced Hsps to Relieve Heat Stress Injury.

Keap1-Nrf2-ARE and heat shock proteins (Hsps) are important endogenous protection mechanisms initiated by heat stress to play a double protective role for cell adaptation and survival. H9C2 cells and 80 300-day-old specific pathogen-free chickens were randomly divided into the control and tea polyphenol groups and used to establish a heat stress model in vitro and in vivo. This task was conducted to explore the protection and mechanism of tea polyphenols in relieving thermal injury. A supplement with 10 µg/mL tea polyphenols could effectively relieve the heat damage of H9C2 cells at 42°C. Accordingly, weaker granular degeneration, vacuolar degeneration, and nucleus deep staining were shown. A strong antioxidant capacity was manifested in the upregulation of the total antioxidant capacity (T-AOC) (at 5 h, P < 0.05), Hemeoxygenase-1 mRNA (at 2 h, P < 0.01), superoxide dismutase (SOD) (at 2, 3, and 5 h, P < 0.05), and Nrf2 (at 0 and 5 h, P < 0.01). A high expression of Hsps was reflected in CRYAB at 3 h; Hsp27 at 0, 2, and 3 h (P < 0.01); and Hsp70 at 3 and 5 h (P < 0.01). The supplement with 0.2 g/L tea polyphenols in the drinking water also had a good effect in alleviating the heat stress damage of the myocardial cells of hens at 38°C. Accordingly, light pathological lesions and downregulation of the myocardial injury-related indicators (LDH, CK, CK-MB, and TNF-α) were shown. The mechanism was related to the upregulation of T-AOC (at 0 h, P < 0.05), GSH-PX (at 0.5 d, P < 0.01), SOD (at 0.5 d), and Nrf2 (at 0 d with P < 0.01 and 2 d with P < 0.05) and the induced expression of CRYAB (at 0.5 and 2 d), Hsp27 (at 0, 0.5, and 5 d), and Hsp70 (at 0 and 0.5 d). In conclusion, the tea polyphenols enhanced the antioxidant capacity and induced Hsps to relieve heat stress injury.

Comparison of mesenchymal stromal cells from peritoneal dialysis effluent with those from umbilical cords: characteristics and therapeutic effects on chronic peritoneal dialysis in uremic rats.

BACKGROUND: A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient's peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD. METHODS: 5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/day) and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2 × 106/rat/week, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses. RESULTS: We showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21, and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSC treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells. CONCLUSIONS: As compared to UC-MSCs, pMSCs may more potently prevent PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients.

Effect of Donor and Recipient ABH-Secretor Status on ABO-Incompatible Living Donor Kidney Transplantation.

Introduction: ABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation. Methods: Data of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection. Results: Of the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004). Conclusions: A weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.

The association between hepatitis C virus infection and renal cell cancer, prostate cancer, and bladder cancer: a systematic review and meta-analysis.

To update the current evidence on whether hepatitis C virus (HCV) infection represents a possible risk factor for renal cell cancer (RCC), prostate cancer (PCa), and bladder cancer (BC). We searched the literature on Pubmed, Web of Science, and Embases before April 2021. A systematic review and meta-analysis were performed. Finally, we extracted 12 studies based on the eligible criteria. Across 11 studies for HCV and RCC, the incorporated RR was 1.28 (95% CI 1.05-1.55), which meant that participants with HCV infection were associated with higher RCC risk. The pooled RR in hazard ratio (HR) subgroup (HR 1.59, 95% CI 1.22-2.08), cohort studies subgroup (RR 1.47, 95% CI 1.18-1.82), and North America subgroup (RR 1.71, 95% CI 1.40-2.09) detected a stronger association between HCV and RCC risk. Although an inverse association was seen for PCa (RR 0.75, 95% CI 0.54-1.03) across seven studies, it was not statistically significant (P = 0.075). There was no significant association between HCV and BC with an incorporated RR of 0.92 (95% CI, 0.82-1.03) across five studies. Our study demonstrated that HCV infection was significantly associated with increased RCC risk. There appeared to be an inverse association for HCV in PCa risk but not statistically significant. No significant association was found between HCV and BC risk. Prospective, large-scale, and well-designed cohort studies are required to validate the association between HCV and RCC, and to investigate the role of HCV on PCa.