COVID-19 Outbreak and Management Approach for Families with Children on Long-Term Kidney Replacement Therapy.

BACKGROUND AND OBJECTIVES: During the coronavirus disease 2019 outbreak, the treatment of families with children on long-term KRT is challenging. This study was conducted to identify the current difficulties, worries regarding the next 2 months, and mental distress experienced by families with children on long-term KRT during the coronavirus disease 2019 outbreak and to deliver possible management approaches to ensure uninterrupted treatment for children on long-term KRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter online survey was conducted between February 10 and 15, 2020, among the families with children on long-term KRT from five major pediatric dialysis centers in mainland China. The primary caregivers of children currently on long-term KRT were eligible and included. Demographic information, severe acute respiratory syndrome coronavirus 2 infection status, current difficulties, and worries regarding the next 2 months were surveyed using a self-developed questionnaire. The Patient Health Questionnaire-9 and the General Anxiety Disorder Scale-7 were used to screen for depressive symptoms and anxiety, respectively. RESULTS: Among the children in the 220 families included in data analysis, 113 (51%) children were on dialysis, and the other 107 (49%) had kidney transplants. No families reported confirmed or suspected cases of coronavirus disease 2019. Overall, 135 (61%) and 173 (79%) caregivers reported having difficulties now and having worries regarding the next 2 months, respectively. Dialysis supply shortage (dialysis group) and hard to have blood tests (kidney transplantation group) were most commonly reported. A total of 29 (13%) caregivers had depressive symptoms, and 24 (11%) had anxiety. After the survey, we offered online and offline interventions to address their problems. At the time of the submission of this paper, no treatment interruption had been reported. CONCLUSIONS: The coronavirus disease 2019 outbreak has had physical, mental, logistical, and financial effects on families with children on long-term KRT.

Risk factors and clinical characteristics of tacrolimus-induced acute nephrotoxicity in children with nephrotic syndrome: a retrospective case-control study.

PURPOSE: Acute nephrotoxicity is a common adverse reaction of tacrolimus therapy; however, its risk factors in pediatric nephrotic syndrome (NS) remain to be evaluated. The objective of this study was to investigate the risk factors and characteristics of tacrolimus-induced acute nephrotoxicity in children with NS. METHODS: Past records of children with NS admitted to our hospital from 2014 to 2018 were reviewed. The incidence and characteristics of nephrotoxicity were analyzed. Multivariate logistic regression analysis was used to identify the risk factors of nephrotoxicity. A clinically applicable risk score was developed and validated. RESULTS: Tacrolimus-induced nephrotoxicity occurred in 25 of 129 patients, 13 patients were grade 1, and the renal function was recovered in 22 patients. Multivariate regression analysis showed that the maximum trough concentrations (C12h) of tacrolimus (OR, 1.48; 95% CI, 1.16 to 1.88; P < 0.001), huaiqihuang granules (OR, 0.095; 95% CI, 0.014 to 0.66; P = 0.017), and diarrhea (OR, 22.00; 95% CI, 1.58 to 306.92; P = 0.022) were independently associated with tacrolimus-induced nephrotoxicity. The maximum C12h were significantly higher in patients with nephrotoxicity (median 9.0 ng/ml) and the cut-off value for acute nephrotoxicity was 6.5 ng/ml. The area under the receiver operating characteristic curve was 0.821 for the proposed model based on the observations used to create the model and 0.817 obtained from k-fold cross-validation. CONCLUSIONS: High trough concentration of tacrolimus and diarrhea can potentiate the risk of tacrolimus-induced acute nephrotoxicity in children with NS, while huaiqihuang granules can protect this condition.

Mitochondrial Transfer of Wharton's Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts.

Wharton's jelly mesenchymal stem cells (WJMSCs) transfer healthy mitochondria to cells harboring a mitochondrial DNA (mtDNA) defect. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major subgroups of mitochondrial diseases, caused by the mt.3243A>G point mutation in the mitochondrial tRNALeu(UUR) gene. The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria. We herein demonstrate that WJMSCs transfer healthy mitochondria into rotenone-stressed fibroblasts of a MELAS patient, thereby eliminating mutation burden and rescuing mitochondrial functions. In the coculture system in vitro study, WJMSCs transferred healthy mitochondria to rotenone-stressed MELAS fibroblasts. By inhibiting actin polymerization to block tunneling nanotubes (TNTs), the WJMSC-conducted mitochondrial transfer was abrogated. After mitochondrial transfer, the mt.3243A>G mutation burden of MELAS fibroblasts was reduced to an undetectable level, with long-term retention. Sequencing results confirmed that the transferred mitochondria were donated from WJMSCs. Furthermore, mitochondrial transfer of WJMSCs to MELAS fibroblasts improves mitochondrial functions and cellular performance, including protein translation of respiratory complexes, ROS overexpression, mitochondrial membrane potential, mitochondrial morphology and bioenergetics, cell proliferation, mitochondrion-dependent viability, and apoptotic resistance. This study demonstrates that WJMSCs exert bioenergetic therapeutic effects through mitochondrial transfer. This finding paves the way for the development of innovative treatments for MELAS and other mitochondrial diseases.

Anti-proliferative constituents from Selaginella moellendorffii.

Two new compounds, (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (1) and rhamnocitrin-3-O-ß-glucopyranosyl-4'-O-ß-galactosyl-(1 --> 3)-glucopyranoside (2), were isolated from the whole plants of Selaginella moellendorffii Hieron. Their structures were determined by spectroscopic methods Additionally, compound 1 could inhibit the proliferation of HT29 cells through inducing cell apoptosis.

Induction of C/EBP homologous protein-mediated apoptosis and autophagy by licochalcone A in non-small cell lung cancer cells.

Licochalcone A (LCA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, presents obvious anti-cancer effects. In this study, the anti-cancer effects and potential mechanisms of LCA in non-small cell lung cancer (NSCLC) cells were studied. LCA decreased cell viability, increased lactate dehydrogenase release, and induced apoptosis in a concentration-dependent manner in NSCLC cells while not in human embryonic lung fibroblast cells. The expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and formation of GFP-LC3 punta, two autophagic markers, were increased after treatment with LCA. LCA-induced LC3-II expression was increased when combined with chloroquine (CQ), while knock-down of autophagy related protein (ATG) 7 or ATG5 reversed LCA-induced LC3-II expression and GFP-LC3 punta formation, suggesting that LCA induced autophagy in NSCLC cells. Inhibition of autophagy could not reverse the LCA-induced cell viability decrease and apoptosis. In addition, LCA increased the expression of endoplasmic reticulum stress related proteins, such as binding immunoglobulin protein and C/EBP homologous protein (CHOP). Knock-down of CHOP reversed LCA-induced cell viability decrease, apoptosis, and autophagy. Taken together, LCA-induced autophagic effect is an accompanied phenomenon in NSCLC cells, and CHOP is critical for LCA-induced cell viability decrease, apoptosis, and autophagy.

Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-κB pathway.

Sepsis is one of the leading causes of mortality in severe systemic inflammatory syndrome. The endotoxin-induced inflammatory response has been linked to the development of sepsis. Rhein is a lipophilic anthraquinone isolated from Rheum rhabarbarum (rhubarb), which has a protective effect on intestinal damage in vivo. However, the underlying mechanism responsible for the protective effects of rhein remains to be elucidated. In the present study, mice were exposed to 20 mg/kg lipopolysaccharide (LPS), prior to being treated with either 100 mg/kg rhein or 0.3 mg/kg toll­like receptor 4 (TLR4) signaling inhibitor TAK­242. In the rhein­treated mice, the colon length (cm) was extended and colon injury was attenuated. In addition, treatment with rhein significantly decreased the expression levels of the LPS­induced inflammatory cytokines interleukin (IL)­1ß, IL­6, IL­8, and tumor necrosis factor­α, in both the plasma and colon tissue. However, mice treated with TAK­242 exhibited increased expression levels of IL­10, as determined by ELISA and western blot analysis. In addition, immunohistochemistry and western blot analyses demonstrated that treatment with rhein was able to reduce TLR4 expression and inhibit nuclear factor­κB (NF­κB) phosphorylation in colon tissue. Furthermore, LPS induction was blocked by TAK­242. These results demonstrate that the observed rhein­attenuated inflammatory response during sepsis may be achieved via the TLR4 NF­κB signaling pathway. In conclusion, the results of the present study provide a novel insight into the protective effects of rhein on LPS­induced intestinal inflammation, and demonstrate that rhein may act as a beneficial therapeutic agent in the treatment of sepsis-induced intestinal damage.

Pu-erh tea powder preventive effects on cisplatin-induced liver oxidative damage in Wistar rats.

BACKGROUND: Chemotherapy is one of the major means for control of malignancies, with cisplatin (CDDP) as one of the main agents, widely used for the treatment of various malignant solid tumors. However, prevention of hepatotoxicity from cisplatin is one of the urgent issues in cancer chemotherapy. In this study, we aimed to investigate the effects of pu-erh tea on hepatotoxicity through body weight and tissue antioxidant parameters like, liver coefficient, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde(MDA) and glutathione (GSH) levels, and light microscopic evaluation by histological findings. MATERIALS AND METHODS: The rats were randomly divided into five groups: Control (n=10), cisplatin (3 mg/kg p.i., n=10), cisplatin+pu-erh (0.32 g/kg/day i.g., n=10), cisplatin+pu-erh (0.8 g/kg/day i.g., n=10) and cisplatin+pu-erh (1.6 g/kg/day i.g., n=10). Pu-erh tea powder was administrated for 31 consecutive days. The rats were sacrificed at the end on the second day after a single dose of cisplatin treatment for measuring indices. RESULTS: Pu-erh tea powder exhibited a protective effect by decreasing MDA and GSH and increasing the SOD and GSH-PX levels and GSH-PX/MDA ratio in comparison with the control group. Besides, pu-erh tea was also able to alleviate the pathological damage to some extent. CONCLUSION: Pu-erh tea powder is protective against cisplatin-induced liver oxidative damages, especially at the medium dosage (0.8 g/kg/d).

[Pharmacokinetic effect of Sappan Lignum on hydroxysafflor yellow A in Carthami Flos].

OBJECTIVE: To investigate the pharmacokinetic effect of Sappan Lignum on hydroxysafflor yellow A (HSYA) in Carthami Flos. METHOD: Concentration of HSYA in rat plasma was detected by RP-HPLC after rats were orally administered with extracts of Carthami Flos or Carthami Flos combined with Sappan Lignum. Pharmacokinetic parameters were calculated by DAS 2.0 pharmacokinetic software. RESULT: In vivo pharmacokinetic models of HSYA were two-compartment open models in both of the Carthami Flos group and the Carthami Flos combined with Sappan Lignum group. After compatibility, HSYA showed a significant lower in apparent volumes of distribution of t(1/2Ka), t(1/2alpha) and V1/F, with slight advance in T(max). CONCLUSION: Sappan Lignum can accelerate absorption, distribution and metabolic process of HSYA in vivo and reduce its accumulation in vivo.

Anti-Inflammatory Effects and Mechanisms of Fatsia polycarpa Hayata and Its Constituents.

Fatsia polycarpa, a plant endemic to Taiwan, is an herbal medicine known for treating several inflammation-related diseases, but its biological function needs scientific support. Thus, the anti-inflammatory effects and mechanisms of the methanolic crude extract (MCE) of F. polycarpa and its feature constituents, that is, brassicasterol (a phytosterol), triterpenoids 3 α -hydroxyolean-11,13(18)-dien-28-oic acid (HODA), 3 α -hydroxyolean-11-en-28,13 ß -olide (HOEO), fatsicarpain D, and fatsicarpain F, were investigated. MCE and HOEO, but not brassicasterol, dose-dependently inhibited lipopolysaccharide- (LPS-)induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophage line, whereas HODA, fatsicarpain D and fatsicarpain F were toxic to RAW cells. Additionally, MCE and HOEO suppressed LPS-induced production of nitric oxide, prostaglandin E2, and interleukin-1 ß and interfered with LPS-promoted activation of the inhibitor kappa B kinase (IKK)/nuclear factor- κ B (NF- κ B) pathway, and that of the mitogen-activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In animal tests, MCE and HOEO effectively ameliorated 12-O-tetradecanoylphorobol-13 acetate- (TPA-)induced ear edema of mice. Thus, MCE of F. polycarpa exhibited an obvious anti-inflammatory activity in vivo and in vitro that likely involved the inhibition of the IKK/NF- κ B pathway and the MAPKs, which may be attributed by triterpenoids such as HOEO.

[Experimental study of mailuoning injection on therapy of hemifacial spasm].

OBJECTIVE: To investigate the protective effect of Mailuoning on the facial nerve demyelination of Hemifacial spasm and provide the data for therapy of Hemifacial spasm. METHOD: 24 New Zealand white rabbits were divided into control group, Saline group and Mailuoning group, on the latter two groups the models of Hemifacial spasm were made by the temporal superficial artery closely contacting the main trunk of facial nerve at stylomastoid foramen. From the 5th week, the Saline and Mailuoning were injected intravenously into ear margin for 2 weeks on Saline and Mailuoning group respectively. At the 7th week, the MDA and SOD in serum were measured, mean while the microstructure and ultrastructure of facial nerve were observed on 3 animal groups. RESULT: The MDA decreased obviously (P < 0.05) and SOD increased significantly (P < 0.01) in Mailuoning group comparing with that of Saline group, while the MDA and SOD showed insignificant changes of Mailuoning group and control group. The facial nerve severely demyelinated and axons retrogressively changed in Saline group but mild in Mailuoning group. CONCLUSION: Mailuoning injection has a significant protective effect on the facial nerve demyelination of Hemifacial spasm and the very important applied value for therapy of Hemifacial spasm.

[Effect of mailuoning injection on calcitonin gene-related peptide expression in facial nerve of rabbits with facial spasm].

OBJECTIVE: To investigate the mechanism of Mailuoning injection (MLN) in protecting facial nerve from injury. METHODS: The New Zealand white rabbit model with facial spasm was established by compressing superficial temporal artery to make artificial demyelinated lesion of the main peripheral facial nerve trunk. The successful establishment was confirmed by using electrophysiological technique to determine abnormal muscle response (AMR) which is a characteristic for facial spasm. MLN was injected continuously through ear marginal vein for 2 weeks. The change of CGRP expression in facial nerve was detected by immunohistochemical technique. RESULTS: As compared with the model group, CGRP expression in facial nerve was significantly increased in the MLN group (P <0.01), and CGRP immunoreactive positive fibers were not seen in the shamoperation group. In the model group, the facial nerve fibers degenerated obviously, myelin sheath loosened and dissociated, the turgent axons with vacuole or even completely disappeared. But the facial nerve lesion was lessened in the MLN group. CONCLUSION: MLN has a significant protective effect on facial nerve demyelination in rabbits with facial spasm, which is closely related with its effect in improving CGRP expression in the facial nerve.