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#35764395   2022/06/28 To Up

The Pathophysiology of Sepsis-Associated AKI.

Sepsis-associated AKI is a life-threatening complication that is associated with high morbidity and mortality in patients who are critically ill. Although it is clear early supportive interventions in sepsis reduce mortality, it is less clear that they prevent or ameliorate sepsis-associated AKI. This is likely because specific mechanisms underlying AKI attributable to sepsis are not fully understood. Understanding these mechanisms will form the foundation for the development of strategies for early diagnosis and treatment of sepsis-associated AKI. Here, we summarize recent laboratory and clinical studies, focusing on critical factors in the pathophysiology of sepsis-associated AKI: microcirculatory dysfunction, inflammation, NOD-like receptor protein 3 inflammasome, microRNAs, extracellular vesicles, autophagy and efferocytosis, inflammatory reflex pathway, vitamin D, and metabolic reprogramming. Lastly, identifying these molecular targets and defining clinical subphenotypes will permit precision approaches in the prevention and treatment of sepsis-associated AKI.
Shuhei Kuwabara, Eibhlin Goggins, Mark D Okusa

1906 related Products with: The Pathophysiology of Sepsis-Associated AKI.

0.1 mg 5 G100 IU500 Units 100 G121100.00 ul

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#35764381   2022/06/27 To Up

Dual leucine zipper kinase regulates Dscam expression through a non-canonical function of the cytoplasmic poly(A)-binding protein.

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The DLK, Wallenda (Wnd) regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3' untranslated region (3'UTR) of mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic analysis shows that Wnd requires for promoting presynaptic arbor growth and for enhancing Dscam expression. Our analysis revealed that mRNAs harbor short poly(A) tails. We identified a region in 3'UTR that specifically interacts with pAbp. Removing this region significantly reduced Wnd-induced increase in Dscam expression. These suggest that a non-canonical interaction of PABP with the 3'UTR of target transcripts is essential for DLK functions.The kinase DLK plays key roles in a multitude of neuronal responses, including axon development, neurodegeneration, and nerve injury. Previous studies show that DLK acts through mRNAs to regulate protein synthesis, but how DLK does so is poorly understood. This study demonstrates that DLK regulates the synthesis of Down syndrome cell adhesion molecule or Dscam through the poly(A)-binding protein PABP-C. Whereas PABP-C is known as a general translational activator, our study shows that DLK-mediated Dscam expression involves a non-canonical interaction between PABP-C and the mRNA, which leads to a selective regulation of translation by PABP-C. Thus, our study provides novel insights into the mechanisms that underlie DLK's function and PABP-C's regulation of gene expression.
Monika Singh, Bing Ye, Jung Hwan Kim

2946 related Products with: Dual leucine zipper kinase regulates Dscam expression through a non-canonical function of the cytoplasmic poly(A)-binding protein.

100ul100 μg0.1 ml100 µg200 100ug100.00 ug100 μg1 mg100ug96T200

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#35764365   // To Up

Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade.

Toll-like receptors (TLRs) are critical innate immune sensors that elicit antitumor immune responses in cancer immunotherapy. Although a few TLR agonists have been approved for the treatment of patients with early-stage superficial cancers, their therapeutic efficacy is limited in patient with advanced invasive cancers. Here, we identified the therapeutic role of a TLR2/3 agonist, L-pampo (LP), which promotes antitumor immunity and enhances the immune checkpoint blockade.
Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim

1049 related Products with: Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade.

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#35764364   // To Up

Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies.

Immune checkpoint blockade (ICB) has achieved unprecedented success in treating multiple cancer types. However, clinical benefit remains modest for most patients with solid malignancies due to primary or acquired resistance. Tumor-intrinsic loss of major histocompatibility complex class I (MHC-I) and aberrations in antigen processing machinery (APM) and interferon gamma (IFN-γ) pathways have been shown to play an important role in ICB resistance. While a plethora of combination treatments are being investigated to overcome ICB resistance, there are few identified preclinical models of solid tumors harboring these deficiencies to explore therapeutic interventions that can bypass ICB resistance. Here, we investigated the combination of the epigenetic modulator entinostat and the tumor-targeted immunocytokine NHS-IL12 in three different murine tumor models resistant to αPD-1/αPD-L1 (anti-programmed cell death protein 1/anti-programmed death ligand 1) and harboring MHC-I, APM, and IFN-γ response deficiencies and differing tumor mutational burden (TMB).
Christine M Minnar, Paul L Chariou, Lucas A Horn, Kristin C Hicks, Claudia Palena, Jeffrey Schlom, Sofia R Gameiro

2184 related Products with: Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies.

96 wells (1 kit)5 96T100ug Lyophilized2ug100.00 ug96 wells (1 kit)10ug5ug1 mg

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#35764327   2022/06/28 To Up

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: X-linked adrenoleukodystrophy (ALD) is a severe orphan disease caused by mutations in the peroxisomal transporter gene, leading to toxic accumulation of Very Long-Chain Fatty Acids (VLCFA - in particular C26:0) resulting in inflammation, mitochondrial dysfunction and demyelination. AMP-activated protein kinase (AMPK) is downregulated in ALD, and its activation is implicated as a therapeutic target. PXL770 is the first direct allosteric AMPK activator with established clinical efficacy and tolerability. : We investigated its effects in ALD patient-derived fibroblasts/lymphocytes and KO mouse glial cells. Readouts included VLCFA levels, mitochondrial function and mRNA levels of proinflammatory genes and compensatory transporters (). Following PXL770 treatment in KO mice, we assessed VLCFA levels in tissues, sciatic nerve axonal morphology by electronic microscopy and locomotor function by open-field/balance-beam tests. : In patients' cells and KO glial cells, PXL770 substantially decreased C26:0 levels (by ~90%), improved mitochondrial respiration, reduced expression of multiple inflammatory genes and induced expression of In KO mice, PXL770 treatment normalized VLCFA in plasma and significantly reduced elevated levels in brain (-25%) and spinal cord (-32%) vs. untreated (p<0.001). Abnormal sciatic nerve axonal morphology was also improved along with amelioration of locomotor function. : Direct AMPK activation exerts beneficial effects on several hallmarks of pathology in multiple ALD models and , supporting clinical development of PXL770 for this disease. Further studies would be needed to overcome limitations including small sample size for some parameters, lack of additional biomarkers and incomplete pharmacokinetic characterization. Adrenoleukodystrophy is a rare and debilitating condition with no approved therapies, caused by accumulation of very long-chain fatty acids. AMPK is downregulated in the disease and has been implicated as a potential therapeutic target. PXL770 is a novel clinical stage direct AMPK activator. In these studies, we used PXL770 to achieve preclinical validation of direct AMPK activation for this disease - based on correction of key biochemical and functional readouts and , thus supporting clinical development.
Pierre-Axel Monternier, Parveen Parasar, Pierre Theurey, Pascale Gluais Dagorn, Navtej Kaur, Tavarekere N Nagaraja, Pascale Fouqueray, Sebastien Bolze, David E Moller, Jaspreet Singh, Sophie Hallakou-Bozec

1296 related Products with: .



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#35764296   2022/06/28 To Up

Maresin 1 intervention Reverses Experimental Pulmonary Arterial Hypertension in mice.

Pulmonary arterial hypertension (PAH) is a pulmonary vasculature obstructive disease that leads to right heart failure and death. Maresin 1 is an endogenous lipid mediator known to promote inflammation resolution. However, the effect of Maresin 1 on PAH remains unclear.
Hui Li, Xinyu Li, Yu Hao, Chenghua Wu, Yuhao Fu, Nana Su, Houlin Chen, Binyu Ying, Haixing Wang, Lihuang Su, Haijian Cai, Qinlian He, Mengsi Cai, Junwei Sun, Jing Lin, Aaron Scott, Fanggao Smith, Xiaoying Huang, Shengwei Jin

2946 related Products with: Maresin 1 intervention Reverses Experimental Pulmonary Arterial Hypertension in mice.

100ug Lyophilized100ug100ug100μg96 wells (1 kit)100ug100ug Lyophilized10mg100ug Lyophilized100ug100ug Lyophilized100ug Lyophilized

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#35764286   2022/06/25 To Up

Fish TRIM21 exhibits antiviral activity against grouper iridovirus and nodavirus infection.

Growing evidences have demonstrated that multiple TRIM (tripartite motif) proteins exert critical roles in host defense against different microbial pathogens. Although mammalian TRIM21 has been reported to function as an important regulatory factor in antiviral immune and inflammatory response, the role of fish TRIM21 against virus infection still remains largely unknown. In the present study, we investigated the characteristics of TRIM21 gene (EcTRIM21) from orange spotted grouper (Epinephelus coioides). The full-length EcTRIM21 cDNA encoded a 557 amino acid peptide with 92.1% and 31.14% identity with giant grouper (Epinephelus lanceolatus) and human (Homo sapiens), respectively. EcTRIM21 contained four conserved domains, including RING, B-Box, PRY and SPRY domain. EcTRIM21 expression was significantly up-regulated in response to Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) infection, suggesting that EcTRIM21 might be involved in host defense against fish virus infections. Subcellular localization showed that EcTRIM21 were distributed in the cytoplasm in a punctate manner. Overexpression of EcTRIM21 in vitro significantly inhibited RGNNV and SGIV replication, as evidenced by the decreased severity of cytopathic effect (CPE) and the reduced expression levels of viral core genes. Consistently, knockdown of EcTRIM21 by small interfering RNA (siRNA) promoted the replication of RGNNV and SGIV in vitro. Furthermore, EcTRIM21 overexpression increased both interferon (IFN) and interferon stimulated response element (ISRE) promoter activities. In addition, the transcription levels of IFN signaling related molecules were positively regulated by EcTRIM21 overexpression. Together, our data demonstrated that fish TRIM21 exerted antiviral activity against fish viruses through positive regulation of host interferon response.
Jiaying Zheng, Linyong Zhi, Wenji Wang, Na Ni, Youhua Huang, Qiwei Qin, Xiaohong Huang

2286 related Products with: Fish TRIM21 exhibits antiviral activity against grouper iridovirus and nodavirus infection.

100 assays2x96 well plates1,000 tests100ug200ug100 assays96 tests1 mg 96 Tests 40 assays

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#35764280   2022/06/25 To Up

Application of moving bed biofilm reactor - nanofiltration - membrane bioreactor with loose nanofiltration hollow fiber membranes for synthetic roxithromycin-containing wastewater treatment: long-term performance, membrane fouling and microbial community.

The present study operated the novel moving bed biofilm reactor-nanofiltration-membrane bioreactor (MBBR-NF-MBR) with loose polyamide NF membranes for the first time to treat roxithromycin (ROX) wastewater. Results showed that both MBBR-NF-MBRs achieved superior COD removal of 98.4% and 97.2% and excellent removal of ROX at 74.1% and 65.5%, respectively. The main membrane fouling mechanism was reversible fouling caused by the combination of abundant polysaccharides, proteins and Ca-P precipitates, which could be effectively removed by acidic cleaning. Sorption and biodegradation were the main removal routes of ROX in MBBR. Partial retention of loose NF membrane contributed to microbial metabolism and increased microbial diversity, especially the genera Hyphomicrobium in attached biofilm, which was reasonable for ROX removal. The cleavage of cladinose, demethylation, phosphorylation and β-oxidation in macrolactone ring were the main biotransformation reactions of ROX. This study provides novel insights for micropollutants wastewater treatment by using loose NF membrane in MBR.
Lei Cao, Yuanling Li, Peining Li, Xueting Zhang, Lei Ni, Li Qi, Haitao Wen, Xinbo Zhang, Yufeng Zhang

1179 related Products with: Application of moving bed biofilm reactor - nanofiltration - membrane bioreactor with loose nanofiltration hollow fiber membranes for synthetic roxithromycin-containing wastewater treatment: long-term performance, membrane fouling and microbial community.

120,814 Membranes/Box0,654 Membranes/Box0,60,8104 Membranes/Box

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#35764278   2022/06/25 To Up

A multifaceted screening of applied voltages for electro-assisted anaerobic digestion of blackwater: significance of temperature, hydrolysis/acidogenesis, electrode corrosion, and energy efficiencies.

A microbial electrolysis cell-assisted anaerobic digester (MEC-AD) was operated with vacuum toilet blackwater at different applied voltages (0-1.6V) at room temperature (R). A parallel MEC-AD was operated at 35 °C (R) to provide a kinetics index at mesophilic temperature. Both reactors failed at 1.6V due to the alkaline pH created by anodic corrosion. In R, the best performance was observed at 1.2V, with methane yield, COD removal, hydrolysis and acidogenesis efficiency increased by 59.9%, 27.0%, 52.0%, and 44.9%, respectively, compared to those of 0V. Enrichment of hydrolytic and syntrophic bacteria (e.g., Clostridium, Bacteroidales, sedimentibacter, syntrophomonas) and increased abundance of genes encoding complex organics (e.g., proteins, carbohydrates, lipids) metabolism in R at 1.2V corresponded to the enhanced hydrolysis/acidogenesis processes. R at 1.2V generated 1.16 times more net energy than R at the optimum voltage for methane yield (0.8V), indicating ambient temperature operation of MEC-AD systems would be a more sustainable strategy.
Qi Huang, Yang Liu, Bipro Ranjan Dhar

2172 related Products with: A multifaceted screening of applied voltages for electro-assisted anaerobic digestion of blackwater: significance of temperature, hydrolysis/acidogenesis, electrode corrosion, and energy efficiencies.

5 G25 mg2 Sample Kit 500 G100 assays1000 tests100μg100 assays

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