cellulase and Disease-Models--Animal

The present work was aimed to investigate the protective effects of enzymatic-hydrolyzed Auricularia polytricha polysaccharides (EnAPS) on renal functions. The characterizations were analyzed by physicochemical methods, and the renoprotections were processed in adenine-induced chronic kidney diseases (CKD) models of mice. Animal experiments exhibited that EnAPS showed superior renal-protections contributing to its antioxidant effects of increasing the enzyme activities and decreasing the lipid contents, and anti-inflammatory effects of reducing proinflammatory cytokines than A. polytricha polysaccharides (APS). Besides, the anti-apoptosis effects of EnAPS was proved by down-regulating Bax and Caspase-3 expressions and up-regulating Bcl-2 expressions by molecular biotechnology, and the anti-fibrosis effects was confirmed by histopathological observations of staining. The characterizations indicated that lower molecular weights possibly contributed to the superior renoprotective effects. These results suggested that enzymatic hydrolysis had potential effects in enhancing the bioactivities, and the polysaccharides could be used in the development of functional foods supplement against CKD.

Topics: Adenine; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Auricularia; Cellulase; Cytokines; Disease Models, Animal; Fibrosis; Glucuronidase; Hydrolysis; Inflammation Mediators; Kidney; Male; Mice; Multienzyme Complexes; Oxidative Stress; Polygalacturonase; Polysaccharides; Renal Insufficiency, Chronic; Signal Transduction

Tuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.

Topics: Animals; Biofilms; Cellulase; Cellulose; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Isoniazid; Mice; Mice, Inbred C57BL; Mycobacterium abscessus; Mycobacterium avium; Mycobacterium fortuitum; Mycobacterium tuberculosis; Rifampin; Tuberculosis, Pulmonary

Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes' epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redox-dead knockin (KI) mouse model that was resistant to this mode of inhibition. The electrophilic lipid 10-nitro-oleic acid (NO2-OA) inhibited hydrolase activity and also lowered BP in an angiotensin II-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid isomer ratios were elevated in plasma from WT but not KI mice following NO2-OA treatment, consistent with the redox-dead mutant being resistant to inhibition by lipid electrophiles. sEH was inhibited in WT mice fed linoleic acid and nitrite, key constituents of the Mediterranean diet that elevates electrophilic nitro fatty acid levels, whereas KIs were unaffected. These observations reveal that lipid electrophiles such as NO2-OA mediate antihypertensive signaling actions by inhibiting sEH and suggest a mechanism accounting for protection from hypertension afforded by the Mediterranean diet.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiomegaly; Cellulase; Diet, Mediterranean; Disease Models, Animal; Epoxide Hydrolases; Fatty Acids; Gene Knock-In Techniques; Hypertension; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nitrates; Nitrites; Sulfhydryl Compounds; Vasoconstrictor Agents; Vasodilation