Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap.

Hydrangea paniculata coumarins alleviate adriamycin-induced renal lipotoxicity through activating AMPK and inhibiting C/EBPβ.

Ethnopharmacological Relevance: Throughout Chinese history, Hydrangea paniculata Siebold has been utilized as a traditional medicinal herb to treat a variety of ailments associated to inflammation. In a number of immune-mediated kidney disorders, total coumarins extracted from Hydrangea paniculata (HP) have demonstrated a renal protective effect.

Aim Of The Study: To investigate renal beneficial effect of HP on experimental Adriamycin nephropathy (AN), and further clarify whether reversing lipid metabolism abnormalities by HP contributes to its renoprotective effect and find out the underlying critical pathways.

Computationally Designed Molecules Modulate ALS-Related Amyloidogenic TDP-43 Aggregation.

Abnormal cytosolic aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is observed in multiple diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and Alzheimer's disease. Previous studies have shown that TDP-43 located at the C-terminal of TDP-43 can form higher-order oligomers and fibrils. Of particular interest are the hexamers that adopt a cylindrin structure that has been strongly correlated to neurotoxicity.

Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.

Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks.

Multiscale simulations reveal TDP-43 molecular-level interactions driving condensation.

The RNA-binding protein TDP-43 is associated with mRNA processing and transport from the nucleus to the cytoplasm. TDP-43 localizes in the nucleus as well as accumulating in cytoplasmic condensates such as stress granules. Aggregation and formation of amyloid-like fibrils of cytoplasmic TDP-43 are hallmarks of numerous neurodegenerative diseases, most strikingly present in >90% of amyotrophic lateral sclerosis (ALS) patients.

Expression and prognosis of inducible T-cell co-stimulator and its ligand in Chinese stage I-III lung adenocarcinoma patients.

Background: Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival. By binding with its ligand (inducible T-cell co-stimulator and its ligand [ICOSL]), an inducible T-cell co-stimulator (ICOS) could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.

Methods: We selected 54 formalin-fixed, paraffin-embedded tumor tissues from cases with stage I-III lung adenocarcinoma cancer.

Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing.

Background: Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA).

7-hydroxycoumarin-β-D-glucuronide protects against cisplatin-induced acute kidney injury via inhibiting p38 MAPK-mediated apoptosis in mice.

Aims: Cisplatin is a widely-used drug in the clinical treatment of tumors, but kidney nephrotoxicity is one of the reasons that limits its widespread use. We previously found that 7-hydroxycoumarin-β-D-glucuronide (7-HCG) was one of metabolites of skimmin and highly enriched in the kidneys and maintained a high blood concentration in skimmin-treated rats. Therefore, we investigated whether 7-HCG has a protective effect on cisplatin-induced acute kidney injury.

Effect of Cosolutes on the Aggregation of a Tau Fragment: A Combined Experimental and Simulation Approach.

The intrinsically disordered protein Tau represents the main component of neurofibrillary tangles that are a hallmark of Alzheimer's disease. A small fragment of Tau, known as paired helical filament 6 (PHF6), is considered to be important for the formation of the β-structure core of the fibrils. Here we study the aggregation of this fragment in the presence of different cosolutes, including urea, TMAO, sucrose and 2-hydroxypropyl-β-cyclodextrin (2-HPβCD), using both experiments and molecular dynamics simulations.

Tachykinin Neuropeptides and Amyloid β (25-35) Assembly: Friend or Foe?

Amyloid β (Aβ) protein is responsible for Alzheimer's disease, and one of its important fragments, Aβ(25-35), is found in the brain and has been shown to be neurotoxic. Tachykinin neuropeptides, including Neuromedin K (NK), Kassinin, and Substance P, have been reported to reduce Aβ(25-35)'s toxicity in cells even though they share similar primary structures with Aβ(25-35). Here, we seek to understand the molecular mechanisms of how these peptides interact with Aβ(25-35) and to shed light on why some peptides with similar primary structures are toxic and others nontoxic.

Terminal Capping of an Amyloidogenic Tau Fragment Modulates Its Fibrillation Propensity.

Aberrant protein folding leading to the formation of characteristic cross-β-sheet-rich amyloid structures is well known for its association with a variety of debilitating human diseases. Often, depending upon amino acid composition, only a small segment of a large protein participates in amyloid formation and is in fact capable of self-assembling into amyloid, independent of the rest of the protein. Therefore, such peptide fragments serve as useful model systems for understanding the process of amyloid formation.

Integrated methodological approach reveals microbial diversity and functions in aerobic groundwater microcosms adapted to vinyl chloride.

Vinyl chloride (VC), a known human carcinogen, is often formed in groundwater (GW) by incomplete reductive dechlorination of chlorinated ethenes. An integrated microbial ecology approach involving bacterial enrichments and isolations, carbon stable-isotope probing (SIP) and metagenome and genome sequencing was applied to ethene-fed GW microcosms that rapidly transitioned to aerobic growth on VC. Actinobacteria, Proteobacteria and Bacteroidetes dominated the microbial communities in ethene- and VC-grown cultures.

Relationships between the Abundance and Expression of Functional Genes from Vinyl Chloride (VC)-Degrading Bacteria and Geochemical Parameters at VC-Contaminated Sites.

Bioremediation of vinyl chloride (VC) contamination in groundwater could be mediated by three major bacterial guilds: anaerobic VC-dechlorinators, methanotrophs, and ethene-oxidizing bacteria (etheneotrophs) via metabolic or cometabolic pathways. We collected 95 groundwater samples across 6 chlorinated ethene-contaminated sites and searched for relationships among VC biodegradation gene abundance and expression and site geochemical parameters (e.g.

Nocardioides, Sediminibacterium, Aquabacterium, Variovorax, and Pseudomonas linked to carbon uptake during aerobic vinyl chloride biodegradation.

Vinyl chloride (VC) is a frequent groundwater contaminant and a known human carcinogen. Bioremediation is a potential cleanup strategy for contaminated sites; however, little is known about the bacteria responsible for aerobic VC degradation in mixed microbial communities. In attempts to address this knowledge gap, the microorganisms able to assimilate labeled carbon ((13)C) from VC within a mixed culture capable of rapid VC degradation (120 μmol in 7 days) were identified using stable isotope probing (SIP).

Epoxyalkane:Coenzyme M Transferase Gene Diversity and Distribution in Groundwater Samples from Chlorinated-Ethene-Contaminated Sites.

Unlabelled: Epoxyalkane:coenzyme M transferase (EaCoMT) plays a critical role in the aerobic biodegradation and assimilation of alkenes, including ethene, propene, and the toxic chloroethene vinyl chloride (VC). To improve our understanding of the diversity and distribution of EaCoMT genes in the environment, novel EaCoMT-specific terminal-restriction fragment length polymorphism (T-RFLP) and nested-PCR methods were developed and applied to groundwater samples from six different contaminated sites. T-RFLP analysis revealed 192 different EaCoMT T-RFs.

Abundance and activity of vinyl chloride (VC)-oxidizing bacteria in a dilute groundwater VC plume biostimulated with oxygen and ethene.

Clean-up of vinyl chloride (VC)-contaminated groundwater could be enhanced by stimulating aerobic VC-oxidizing bacterial populations (e.g., methanotrophs) with amendments such as molecular oxygen.

Elucidating carbon uptake from vinyl chloride using stable isotope probing and Illumina sequencing.

Vinyl chloride (VC), a known human carcinogen, is a common and persistent groundwater pollutant at many chlorinated solvent contaminated sites. The remediation of such sites is challenging because of the lack of knowledge on the microorganisms responsible for in situ VC degradation. To address this, the microorganisms involved in carbon assimilation from VC were investigated in a culture enriched from contaminated site groundwater using stable isotope probing (SIP) and high-throughput sequencing.

Partial nitritation ANAMMOX in submerged attached growth bioreactors with smart aeration at 20 °C.

Submerged attached growth bioreactors (SAGBs) were operated at 20 °C for 30 weeks in smart-aerated, partial nitritation ANAMMOX mode and in a timer-controlled, cyclic aeration mode. The smart-aerated SAGBs removed 48-53% of total nitrogen (TN) compared to 45% for SAGBs with timed aeration. Low dissolved oxygen concentrations and cyclic pH patterns in the smart-aerated SAGBs suggested conditions favorable to partial nitritation ANAMMOX and stoichiometrically-derived and numerically modeled estimations attributed 63-68% and 14-44% of TN removal to partial nitritation ANAMMOX in these bioreactors, respectively.