Critical roles of tubular mitochondrial ATP synthase dysfunction in maleic acid-induced acute kidney injury.

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.

Exercise Normalized the Hippocampal Renin-Angiotensin System and Restored Spatial Memory Function, Neurogenesis, and Blood-Brain Barrier Permeability in the 2K1C-Hypertensive Mouse.

Hypertension is associated with blood-brain barrier alteration and brain function decline. Previously, we established the 2-kidney,1-clip (2K1C) hypertensive mice model by renin-angiotensin system (RAS) stimulating. We found that 2K1C-induced hypertension would impair hippocampus-related memory function and decrease adult hippocampal neurogenesis. Even though large studies have investigated the mechanism of hypertension affecting brain function, there remains a lack of efficient ways to halt this vicious effect. The previous study indicated that running exercise ameliorates neurogenesis and spatial memory function in aging mice. Moreover, studies showed that exercise could normalize RAS activity, which might be associated with neurogenesis impairment. Thus, we hypothesize that running exercise could ameliorate neurogenesis and spatial memory function impairment in the 2K1C-hypertension mice. In this study, we performed 2K1C surgery on eight-weeks-old C57BL/6 mice and put them on treadmill exercise one month after the surgery. The results indicate that running exercise improves the spatial memory and neurogenesis impairment of the 2K1C-mice. Moreover, running exercise normalized the activated RAS and blood-brain barrier leakage of the hippocampus, although the blood pressure was not decreased. In conclusion, running exercise could halt hypertension-induced brain impairment through RAS normalization.

Size Preferences Uptake of Glycosilica Nanoparticles to MDA-MB-231 Cell.

Recently, studies on the development and investigation of carbohydrate-functionalized silica nanoparticles (NPs) and their biomedicine applications such as cell-specific targeting and bioimaging has been carried out extensively. Since the number of breast cancer patients has been growing in recent years, potential NPs were being studied in this project for targeting breast cancer cells. Mannose receptors can be found on the surface of MDA-MB-231, which is a kind of human breast cancer cell line. Therefore, we decorated a cyanine 3 fluorescent dye (Cy3) and mannosides on the surface of silica NPs for the purpose of imaging and targeting. Galactoside was also introduced onto the surface of silica NPs acting as a control sample. Various sizes of silica NPs were synthesized by using different amounts of ammonium to investigate the effect of the size of NPs on the cellular uptake rate. The physical properties of these NPs were characterized by scanning electron microscope, dynamic light scattering, and their zeta potential. Cellular experiments demonstrated that mannoside-modified NPs can be uptaken by MDA-MB-231. From the experiment, we found out that the best cellular uptake rate of nanoparticle size is about 250 nm. The MTT assay showed that Man@Cy3SiO2NPs are not cytotoxic, indicating they may have the potential for biomedical applications.

Mannoside-Modified Branched Gold Nanoparticles for Photothermal Therapy to MDA-MB-231 Cells.

Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl4 in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV-vis absorption peak was detected in the range of 700-1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur-Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231.

Eicosapentaenoic acid reduces indoleamine 2,3-dioxygenase 1 expression in tumor cells.

Marine plants and animals have omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is required for biological processes, but humans are unable to synthesize them and must be obtained from dietary sources. EPA has been used as an antitumor agent but the molecular mechanisms for the regulation of tumor microenvironment immunity by EPA are still unknown. The indoleamine 2,3-dioxygenase 1 (IDO) catalyzes conversion of tryptophan to kynurenine to induce immune evasion in tumor microenvironment. In this study, EPA inhibited the expression of IDO via downregulation of protein kinase B (Akt)/mammalian targets of rapamycin (mTOR) signaling pathway in tumor cells. Meanwhile, a significant decrease in kynurenine levels and increase in T cell survival were observed after tumor cells treated with EPA. The results demonstrated that EPA can activate host antitumor immunity by inhibiting tumor IDO expression. Therefore, our finding suggests that EPA can be enormous potential for cancer immunotherapy.

The Extracts of Astragalus membranaceus Inhibit Melanogenesis through the ERK Signaling Pathway.

Melanin is a normal production protecting skin from environment-causing damage. Plants produce some agents in response to their environment. These agents could be applied in cosmetic production. Some Chinese herbals have immunomodulatory activities and modulate the symptoms of several diseases. Melanogenesis represents a complex group of conditions that are thought to be mediated through a complex network of regulatory processes. Previously, some studies found that the extracts of Astragalus membranaceus (PG2) regulated immunity and supported hematopoiesis. Herein, we want to determine the molecular mechanisms by which PG2 inhibits melanogenesis in B16F10 melanoma cells. The cellular melanin contents and expression of melanogenesis-related protein, including microphthalmia associated transcription factor (MITF) and tyrosinase were significantly reduced after PG2 treatment. Moreover, PG2 increased phosphorylation of ERK, without affecting phosphorylation of p38. These results suggested that PG2 as a new target in reducing hyperpigmentation through the ERK signal pathway. PG2 has potential for cosmetic usage in the future.

The inhibition of indoleamine 2, 3-dioxygenase 1 by connexin 43.

Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. The expression of indoleamine 2, 3-dioxygenase (IDO) is one of the crucial factors contributing to tumor immune tolerance by depletion of tryptophan and IDO-mediated tryptophan metabolites. Here, we aim to investigate the role of Cx43 in IDO production in murine tumor by using Cx43 inducers. Resveratrol (trans-3, 5, 4 '-trihydroxystilbene) is a natural plant-derived polyphenol possessing positive effect against cancer. Salmonella enterica serovar choleraesuis (S.C.) was proved to target and inhibit tumor growth. Both of them regulated Cx43 expression in tumor cells and led to either chemosensitizing or immune-activating. In this study, the correlation between Cx43 and IDO were determined by the treatment of resveratrol and S.C. Our data showed an increase in Cx43 while IDO protein and IDO-mediated inhibited effects on T cell decreased after tumor cells are given with resveratrol and S.C. TREATMENTS: All of which could be inhibited once the expression of Cx43 was blocked. Cx43 involved in IDO regulation might be useful in developing IDO-targeted cancer immune therapy.

Postconditioning mitigates cell death following oxygen and glucose deprivation in PC12 cells and forebrain reperfusion injury in rats.

Postconditioning mitigates ischemia-induced cellular damage via a modified reperfusion procedure. Mitochondrial permeability transition (MPT) is an important pathophysiological change in reperfusion injury. This study explores the role of MPT modulation underlying hypoxic postconditioning (HPoC) in PC12 cells and studies the neuroprotective effects of ischemic postconditioning (IPoC) on rats. Oxygen-glucose deprivation (OGD) was performed for 10 hr on PC12 cells. HPoC was induced by three cycles of 10-min reoxygenation/10-min rehypoxia after OGD. The MPT inhibitor N-methyl-4-isoleucine cyclosporine (NIM811) and the MPT inducer carboxyatractyloside (CATR) were administered to selective groups before OGD. Cellular death was evaluated by flow cytometry and Western blot analysis. JC-1 fluorescence signal was used to estimate the mitochondrial membrane potential (△Ψm ). Transient global cerebral ischemia (tGCI) was induced via the two-vessel occlusion and hypotension method in male Sprague Dawley rats. IPoC was induced by three cycles of 10-sec reperfusion/10-sec reocclusion after index ischemia. HPoC and NIM811 administration attenuated cell death, cytochrome c release, and caspase-3 activity and maintained △Ψm of PC12 cells after OGD. The addition of CATR negated the protection conferred by HPoC. IPoC reduced neuronal degeneration and cytochrome c release and cleaved caspase-9 expression of hippocampal CA1 neurons in rats after tGCI. HPoC protected PC12 cells against OGD by modulating the MPT. IPoC attenuated degeneration of hippocampal neurons after cerebral ischemia.

Dialysate Lavage: An Alternative Solution for Reducing the Peritoneal Implantation of Poorly Differentiated Gastric Cancer Cells.

BACKGROUND: Peritoneal lavage after cancer surgery is performed to reduce microscopic residual tumors in the peritoneum. This study evaluated the effects and mechanism of dialysate lavage in reducing the peritoneal implantation of gastric cancer cells. METHODS: Gastric cancer cells (MKN45 or AGS) were cultured with 1.5% peritoneal dialysate (PD) or normal saline (NS) for 30 min. The in vitro cell susceptibility to dialysate, including cell proliferation, cell death, cleaved PARP expression, and mitochondrial membrane potential, was evaluated. A murine model for gastric cancer cell peritoneal seeding was established to test the effects of PD and NS lavage on animal survival and tumor growth. RESULTS: A significant decrease in cell proliferation in PD and NS (75.2 ± 0.1 vs. 12.4 ± 0.2% in MKN45, p = 0.009; 58.2 ± 0.01 vs. 28.0 ± 0.01% in AGS, p = 0.008), an increase in mitochondrial permeability transition (93.0 ± 2.6 vs. 18.0 ± 2.9% in MKN45, p = 0.021; 86.8 ± 4.6 vs. 47.7 ± 10.2% in AGS, p < 0.001), and an increase in the expression of cleaved PARP and increased death (25.6 ± 9.4 vs. 16.9 ± 5.3% in MKN45, p = 0.031; 39.5 ± 5.1 vs. 20.9 ± 3.9% in AGS, p = 0.008) were recorded for gastric cancer cells separately exposed to PD and NS. Twenty-four days after inoculating MKN45 cells (5 × 10(6)/0.1 ml) in the peritoneal cavity, the average number of seeded tumors was 67.3 ± 10.8, 92.3 ± 6.0, and 29.2 ± 16.7 (p = 0.032), and the total weight of tumors was 0.98 ± 0.21, 0.58 ± 0.12, and 0.31 ± 0.17 g (p = 0.008), respectively, for mice receiving sham operation, NS lavage, and PD lavage. The 45-day survival rate for the PD lavage group was 22% compared to 0% for the sham injection and NS lavage groups (p = 0.034). CONCLUSION: PD induced significant cytotoxicity in gastric cancer cells that was related to mitochondrial perturbation. The use of PD lavage was effective in reducing the peritoneal implantation of gastric cancers in a murine model.

High deposition and precise stimulus-response release performance of lignin-coated dendritic mesoporous organosilica nanoparticles for efficient pesticide utilization.

The inefficient and improper use of conventional pesticides has prompted the development of targeted and cost-effective pesticide delivery systems, which aim to optimize the efficient utilization of pesticides while minimizing environmental pollution in surrounding areas. In this paper, a dual-stimuli-responsive pesticide slow-release nanopesticide system (NES@DMONs@LGN) was designed in this study, utilizing mesoporous silica (DMONs) as a nanocarrier and lignin (LGN) as a capping agent to encapsulate the pesticide molecules within DMONs. This system enables intelligent release of pesticide molecules while preventing environmental pollution caused by leakage. Additionally, NES@DMONs@LGN exhibit excellent specific loading efficiency. The abundant hydrophilic functional groups in the lignin layer on the surface of NES@DMONs@LGN can establish hydrogen bonds with advanced fatty acids and fatty alcohols present in the waxy epidermis of plants, thereby significantly enhancing carrier wettability and adhesion. Typically, phytophagous lepidopteran pests have an alkaline midgut and possess lignin-degrading enzymes. The NES@DMONs@LGN developed in this study are capable of rapid release under high temperature and alkaline conditions. Therefore, the precise release of pesticide molecules in the target pests can be achieved, thus increasing the actual utilization rate of pesticides. The experimental results demonstrated that NES@DMONs@LGN effectively prevented photodegradation of the active ingredient after 48 h of UV irradiation, resulting in a 3.7-fold improvement in photostability and providing robust UV protection. By encapsulating pesticide molecules with nanocarriers, the release of pesticides in non-targeted environments can be prevented, thereby significantly reducing toxicity to zebrafish. Thus, this study provides a promising solution for sustainable greening of agriculture.

Advances in the Design of Functional Cellulose Based Nanopesticide Delivery Systems.

The advancement of science and technology, coupled with the growing environmental consciousness among individuals, has led to a shift in pesticide development from traditional methods characterized by inefficiency and misuse toward a more sustainable and eco-friendly approach. Cellulose, as the most abundant natural renewable resource, has opened up a new avenue in the field of biobased drug carriers by developing cellulose-based drug delivery systems. These systems offer unique advantages in terms of deposition rate enhancement, modification facilitation, and environmental impact reduction when designing nanopesticides. Consequently, their application in the field of nanoscale pesticides has gained widespread recognition. The present study provides a comprehensive review of cellulose modification methods, carrier types for cellulose-based nanopesticides delivery systems (CPDS), and various stimulus-response factors influencing pesticide release. Additionally, the main challenges in the design and application of CPDS are summarized, highlighting the immense potential of cellulose-based materials in the field of nanopesticides.

A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress.

Glioblastoma is a Grade 4 primary brain tumor defined by therapy resistance, diffuse infiltration, and near-uniform lethality. The underlying mechanisms are unknown, and no treatment has been curative. Using a recently developed creatine kinase inhibitor (CKi), we explored the role of this inhibitor on GBM biology in vitro. While CKi minimally impacted GBM cell proliferation and viability, it significantly affected migration. In established GBM cell lines and patient-derived xenografts, CKi ablated both the migration and invasion of GBM cells. CKi also hindered radiation-induced migration. RNA-seq revealed a decrease in invasion-related genes, with an unexpected increase in glutathione metabolism and ferroptosis protection genes post-CKi treatment. The effects of CKi could be reversed by the addition of cell-permeable glutathione. Carbon-13 metabolite tracing indicated heightened glutathione biosynthesis post-CKi treatment. Combinatorial CKi blockade and glutathione inhibition or ferroptosis activation abrogated cell survival. Our data demonstrated that CKi perturbs promigratory and anti-ferroptotic roles in GBM, identifying the creatine kinase axis as a druggable target for GBM treatment.

Myeloid cell-derived creatine in the hypoxic niche promotes glioblastoma growth.

Glioblastoma (GBM) is a malignancy dominated by the infiltration of tumor-associated myeloid cells (TAMCs). Examination of TAMC metabolic phenotypes in mouse models and patients with GBM identified the de novo creatine metabolic pathway as a hallmark of TAMCs. Multi-omics analyses revealed that TAMCs surround the hypoxic peri-necrotic regions of GBM and express the creatine metabolic enzyme glycine amidinotransferase (GATM). Conversely, GBM cells located within these same regions are uniquely specific in expressing the creatine transporter (SLC6A8). We hypothesized that TAMCs provide creatine to tumors, promoting GBM progression. Isotopic tracing demonstrated that TAMC-secreted creatine is taken up by tumor cells. Creatine supplementation protected tumors from hypoxia-induced stress, which was abrogated with genetic ablation or pharmacologic inhibition of SLC6A8. Lastly, inhibition of creatine transport using the clinically relevant compound, RGX-202-01, blunted tumor growth and enhanced radiation therapy in vivo. This work highlights that myeloid-to-tumor transfer of creatine promotes tumor growth in the hypoxic niche.

GPR35 antagonist CID-2745687 attenuates anchorage-independent cell growth by inhibiting YAP/TAZ activity in colorectal cancer cells.

Background and purpose: GPR35, a member of the orphan G-protein-coupled receptor, was recently implicated in colorectal cancer (CRC). However, whether targeting GPR35 by antagonists can inhibit its pro-cancer role has yet to be answered. Experimental approach: We applied antagonist CID-2745687 (CID) in established GPR35 overexpressing and knock-down CRC cell lines to understand its anti-cell proliferation property and the underlying mechanism. Key results: Although GPR35 did not promote cell proliferation in 2D conditions, it promoted anchorage-independent growth in soft-agar, which was reduced by GPR35 knock-down and CID treatment. Furthermore, YAP/TAZ target genes were expressed relatively higher in GPR35 overexpressed cells and lower in GPR35 knock-down cells. YAP/TAZ activity is required for anchorage-independent growth of CRC cells. By detecting YAP/TAZ target genes, performing TEAD4 luciferase reporter assay, and examining YAP phosphorylation and TAZ protein expression level, we found YAP/TAZ activity is positively correlated to GPR35 expression level, which CID disrupted in GPR35 overexpressed cells, but not in GPR35 knock-down cells. Intriguingly, GPR35 agonists did not promote YAP/TAZ activity but ameliorated CID's inhibitory effect; GPR35-promoted YAP/TAZ activity was only partly attenuated by ROCK1/2 inhibitor. Conclusion and implications: GPR35 promoted YAP/TAZ activity partly through Rho-GTPase with its agonist-independent constitutive activity, and CID exhibited its inhibitory effect. GPR35 antagonists are promising anti-cancer agents that target hyperactivation and overexpression of YAP/TAZ in CRC.

Aminosalicylates target GPR35, partly contributing to the prevention of DSS-induced colitis.

GPR35, a class A G-protein-coupled receptor, is considered an orphan receptor; the endogenous ligand and precise physiological function of GPR35 remain obscure. GPR35 is expressed relatively highly in the gastrointestinal tract and immune cells. It plays a role in colorectal diseases like inflammatory bowel diseases (IBDs) and colon cancer. More recently, the development of GPR35 targeting anti-IBD drugs is in solid request. Nevertheless, the development process is in stagnation due to the lack of a highly potent GPR35 agonist that is also active comparably in both human and mouse orthologs. Therefore, we proposed to find compounds for GPR35 agonist development, especially for the human ortholog of GPR35. As an efficient way to pick up a safe and effective GPR35 targeting anti-IBD drug, we screened Food and Drug Administration (FDA)-approved 1850 drugs using a two-step DMR assay. Interestingly, we found aminosalicylates, first-line medicine for IBDs whose precise target remains unknown, exhibited activity on both human and mouse GPR35. Among these, pro-drug olsalazine showed the most potency on GPR35 agonism, inducing ERK phosphorylation and ß-arrestin2 translocation. In dextran sodium sulfate (DSS)-induced colitis, the protective effect on disease progression and inhibitory effect on TNFα mRNA expression, NF-κB and JAK-STAT3 pathway of olsalazine are compromised in GPR35 knock-out mice. The present study identified a target for first-line medicine aminosalicylates, highlighted that uncleaved pro-drug olsalazine is effective, and provided a new concept for the design of aminosalicylic GPR35 targeting anti-IBD drug.

Exploring the Impact of Glyoxal Glycation on ß-Amyloid Peptide (Aß) Aggregation in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the presence of extracellular senile plaques formed by ß-amyloid (Aß) peptides in the patient's brain. Previous studies have shown that the plaques in the AD brains are colocalized with the advanced glycation end products, which is mainly formed from a series of nonenzymatic reactions of proteins with reducing sugars or reactive dicarbonyls. Glycation was also demonstrated to increase the neurotoxicity of the Aß peptides. To clarify the impact of glycation on Aß aggregation, we synthesized two glycated Aß42 peptides by replacing Lys16 and Lys28 with Nε-carboxymethyllysine respectively to mimic the occurrence of protein glycation. Afterward, we monitored the aggregation kinetics and conformational change for two glycated peptides. We also used fluorescence correlation spectroscopy to probe the early stage of peptide oligomerization and tested their abilities in copper binding and reactive oxygen species production. Our data show that glycation significantly slows down the aggregation process and induces more cytotoxicity especially at position 28. We speculated that the higher toxicity might result from a relatively stable oligomeric form of peptide and not from ROS production. The data shown here emphasized that glycated proteins would be an important therapeutic target in AD treatments.

Chlorpromazine, an antipsychotic agent, induces G2/M phase arrest and apoptosis via regulation of the PI3K/AKT/mTOR-mediated autophagy pathways in human oral cancer.

Chlorpromazine (CPZ), an FDA-approved phenothiazine derivative used to treat schizophrenia and other psychiatric disorders, has been demonstrated to have potential anti-tumor effects. However, the potential effects of CPZ on human oral cancer cells and the underlying molecular mechanisms remain unknown. In this study, treatment of human oral cancer cells with CPZ inhibited their proliferation and induced G2/M phase arrest. Treatment with CPZ induced apoptosis through the extrinsic death receptor and the intrinsic mitochondrial pathways. In addition, the induction of autophagy was observed by the formation of autophagosomes, the expression of autophagy-related proteins and activation of the PI3K/Akt/mTOR/p70S6K pathway. The CPZ-induced cell death was reversed by the pan-caspase inhibitor Z-VAD-FMK, by the autophagy inhibitor 3-MA and by the knockdown of LC3B using a shRNA (shLC3B), suggesting that autophagy promoted CPZ-induced apoptosis. Finally, CPZ significantly suppressed tumor growth in both a zebrafish oral cancer xenotransplantation model and in a murine model of 4-nitroquinoline-1-oxide (4NQO)-induced oral cancer. Overall, this evidence demonstrated that CPZ is a novel promising strategy for the treatment of oral cancer.

Mannosyl electrochemical impedance cytosensor for label-free MDA-MB-231 cancer cell detection.

A label-free and ultrasensitive electrochemical impedance cytosensor was developed to specifically detect the breast cancer cells MDA-MB-231 via the interaction between the mannosyl glassy carbon electrode (GCE) and the overexpressed mannose receptors on the target cell surface. The mannosyl GCE was prepared through electrografting of the amino-functionalized mannose derivatives on GCE surface in which a covalent bond was formed between carbon of the electrode and the amino group of the mannose derivative. The fluorescent microscopy indicated that the electrode is specific for MDA-MB-231 cells, with good biocompatibility for viable captured cells. The derivative with a shorter alkyl linker, mannose-C2NH2, showed a better sensitivity than that with a longer linker, mannose-C6NH2. GCE modified with amino-functionalized galactose derivative, galactose-C2NH2, shows no function to the detection of MDA-MB-231 cells. The specific interaction between the mannosyl GCE and Con A (a mannose-binding lectin) or MDA-MB-231 breast cancer cells with overexpressed mannose receptors was determined through the change of peak separation in the cyclic voltammogram or the change of charge transfer resistance in the electrochemical impedance spectra (Nyquist plot) in the electrolytes containing a reversible redox couple [Fe(CN)6]3-/[Fe(CN)6]4-. The charge transfer resistance in the Nyquist plots linearly depended on the concentration of MDA-MB-231 cells (1.0 × 10-1.0 × 105 cells mL-1, with 10 cells mL-1 being the lower detection limit). Introducing 0.1% polyethylene glycol-200 (PEG-200) was able to prevent the interference caused by 1.0 × 103 HEK-293T cells mL-1, a non-cancer cell line (control).

Factors and outcomes associated with candidemia caused by non-albicans Candida spp versus Candida albicans in children.

BACKGROUND: Candidemia in children caused by non-albicans Candida (NAC) spp is increasing in prevalence, but the relevant information is limited. METHODS: All isolates of pediatric candidemia from a medical center in Taiwan between 2003 and 2015 were enrolled. The characteristics of patients with NAC and Candida albicans candidemia (CAC) were compared. RESULTS: Among the 319 episodes of candidemia occurring in 262 patients, C albicans accounted for 46.4%. The NAC and CAC groups had no significant differences in demographics, underlying diseases, most risk factors, and clinical characteristics. Patients in the NAC group were significantly more likely to have fluconazole exposure (14.0% vs 6.8%, respectively; P = .045), and NAC species accounted for 70.2% of all recurrent episodes. NAC candidemia had a longer duration of candidemia (median, 3.0 vs 1.0 days after effective antifungal treatment, respectively; P = .001), slower responses to antifungal treatment, and a higher rate of treatment failure than CAC. However, the 2 groups had similar 30-day candidemia-attributable mortality rates. After multivariate logistic regression, longer duration of central venous catheter was the independent risk factor for NAC candidemia in children (odds ratio, 1.21; 95% confidence interval, 1.08-1.35 for every 10-day increment). CONCLUSIONS: NAC species collectively have emerged as the predominant pathogens of candidemia in children. Prolonged use of a central venous catheter is associated with an increased risk of candidemia caused by NAC species.

microRNA-183 Mediates Protective Postconditioning of the Liver by Repressing Apaf-1.

AIMS: Ischemic postconditioning (iPoC) is known to mitigate ischemia-reperfusion (IR) injury of the liver, the mechanisms of which remain to be elucidated. This study explored the role of microRNA-183 (miR-183) in the protective mechanism of iPoC. RESULTS: Microarray analysis showed miR-183 was robustly expressed in rats' livers with iPoC. miR-183 repressed the mRNA expression of Apaf-1, which is an apoptosis promoting factor. Using an oxygen-glucose deprivation (OGD) injury model in Clone 9 cells, hypoxic postconditioning (HPoC) and an miR-183 mimetic significantly decreased cell death after OGD, but miR-183 inhibitors eliminated the protection of HPoC. The increased expression of Apaf-1 and the downstream activation of capsase-3/9 after OGD were mitigated by HPoC or the addition of miR-183 mimetics, whereas miR-183 inhibitor diminished the effect of HPoC on Apaf-1-caspase signaling. In the in vivo experiment, iPoC and agomiR-183 decreased the expression of serum ALT after liver IR in the mice, but antagomiR-183 mitigated the effect of iPoC. The results of hematoxylin and eosin and TUNEL staining were compatible with the biochemical assay. Moreover, iPoC and agomiR-183 decreased the expression of Apaf-1 and 4-HNE after IR injury in mouse livers, whereas the antagomiR-mediated prevention of miR-183 expression led to increased protein expression of Apaf-1 and 4-HNE in the postischemic livers. INNOVATION: Our experiment showed the first time that miR-183 was induced in protective postconditioning and reduced reperfusion injury of the livers via the targeting of apoptotic signaling. CONCLUSION: miR-183 mediated the tolerance induced by iPoC in livers via Apaf-1 repressing. Antioxid. Redox Signal. 26, 583-597.