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1.
Lab Invest ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013530

RESUMO

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

2.
Mol Neurobiol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013936

RESUMO

Cerebral ischemia reperfusion (I/R) injury easily develops in ischemic stroke, resulting in more serious injury. Ferroptosis is involved in cerebral I/R injury, but the mechanism remains unclear. Prostaglandin E2 (PGE2) is potential to regulate ferroptosis. This study mainly explored the regulation effects of PGE2 on ferroptosis induced by cerebral I/R. We first detected PGE2 levels and ferroptosis status in 11 human brain tissues. Then, we induced a cerebral I/R animal model to examine ferroptosis status in cerebral I/R. We further injected a ferroptosis inhibitor to define the response of the PGE2 pathway to ferroptosis. Finally, we injected PGE2 and pranoprofen to explore the regulation of the cyclooxygenases 2 (COX-2)/PGE2 pathway on ferroptosis in cerebral I/R. We found that PGE2 release was correlated with the levels of reactive oxygen species, malondialdehyde, glutathione peroxidase 4, COX-2, and Spermidine/spermine N1-acetyltransferase 1. Ferroptosis can be induced by cerebral I/R, while inhibition of ferroptosis induced by cerebral I/R can inactivate PGE2 synthases, degrade enzyme, and parts of PGE2 receptors, and reduce cerebral infarct volume. In turn, PGE2 inhibited ferroptosis through the reduction of Fe2+, glutathione oxidation, and lipid peroxidation, while pranoprofen, one of the COX inhibitors, played an opposite role. In conclusion, PGE2 was positively correlated with ferroptosis, inhibition of ferroptosis induced by cerebral I/R can inactivate COX-2/PGE2 pathway, and PGE2 inhibited ferroptosis induced by cerebral I/R, possibly via PGE2 receptor 3 and PGE2 receptor 4. Graphical abstract Inhibition of ferroptosis inactivates the COX-2/PGE2 pathway. Cerebral ischemia reperfusion injury induces the secretion of PGE2. After the inhibition of ferroptosis by Fer-1, the expression of cyclooxygenases (COX-1 and COX-2) decreased, and PGE2 synthases cPGES, mPGES-1, and mPGES-2 were also reduced. At the same time, the PGE2 degradation enzyme 15-PGDH was also reduced. Changes in these enzymes ultimately result in the declination of PGE2. Besides, the expression of PGE2 receptors EP3 and EP4 is also inhibited, indicating that the function they mediate is also impaired. In conclusion, after cerebral ischemia reperfusion injury, the inhibition of ferroptosis inactivates the COX-2/PGE2 pathway.

3.
Can J Microbiol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34995146

RESUMO

Anaerobic cellulolytic microbes in gastrointestinal tract (GT) of ruminants have been well-documented, however, knowledge of aerobic microbes with cellulolytic activities in ruminant GT is comparably limited. Here, we unraveled aerobic cultivable cellulolytic microbes in GT of Ujimqin sheep (Ovis aries) and evaluated the cellulolytic potential of promising isolates. Twenty-two strains were found to possess cellulose degrading potential by Congo-red staining and phylogenetic analysis of the 16S rDNA/ITS sequence revealed that all strains belonged to nine genera, i.e., Bacillus, Streptomyces, Pseudomonas, Lactobacillus, Brachybacterium, Sanguibacter, Rhizobium, Fusarium, and Aspergillus. Strains with high cellulolytic activities were selected to further evaluate the various enzyme activities on lignocellulosic alfalfa hay (Medicago sativa). Among them, isolate Bacillus subtilis RE2510 showed the highest potential of cellulose degradation considering the high endoglucanase (0.1478 ± 0.0014 IU ml-1), exoglucanase (0.1735 ± 0.0012 IU ml-1) and ß-glucosidase (0.3817 ± 0.0031 IU ml-1) after 10-day incubation with alfalfa hay. A significant destruction effect of the cellulose structure and the attachment of B. subtilis RE2510 to the hay were also revealed by using scanning electron microscope. This study expands our knowledge of aerobic cellulolytic isolates from GT of sheep and also highlights their potential application as microbial additive in the aerobic process of cellulose bioconversion.

4.
Plant Dis ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35021876

RESUMO

In 2017, a new race (TSA-6) of the wheat stripe rust pathogen, Puccinia striiformis f. sp. tritici, virulent to resistance gene Yr5 were detected in China. However, whether Chinese wheat cultivars are resistant to the new races was unknown. In this study, two isolates (TSA-6 and TSA-9) with virulence to Yr5 were tested on other wheat Yr gene lines for their avirulence/virulence patterns and used, together with prevalent races CYR32 and CYR34 without the Yr5 virulence, to evaluate 165 major Chinese wheat cultivars for their reactions. Isolates TSA-6 and TSA-9 had similar but different virulence spectra, and therefore should be considered as two different races. Their avirulent/virulence patterns were remarkably different from that of CYR34 but quite similar to that of CYR32. Of the 165 wheat cultivars, 21 had all-stage resistance to TSA-6, 34 to TSA-9, and 20 to both races. Adult-plant resistance (APR) was detected in 35 cultivars to TSA-6 and 27 to TSA-9, but only 3 cultivars showed APR to both new races. Slow rusting resistance was observed in 24 cultivars to TSA-6 and of 33 to TSA-9. Analysis of variance (ANOVA) of disease index indicated a significant difference among cultivars, but not among the four races. Based on the molecular marker data, a low percentage of wheat cultivars carried Yr5, Yr7, Yr10, Yr15, Yr26, and/or YrSP. As TSA-6 and TSA-9 can be a serious threat to wheat production in China, monitoring TSA-6, TSA-9, and other races are continually needed.

5.
Hum Cell ; 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032011

RESUMO

Despite increasing evidence that dysbiosis of urinary microbiota is closely correlated with bladder cancer, the influence of the urinary microbiota on immune evasion and tumor growth in bladder cancer is unknown. This study investigated whether the urinary microbiota influences intratumoral infiltration of FoxP3+ regulatory T cells, expression of Ki-67 and clinical prognosis in non-muscle-invasive bladder cancer. Forty male patients, including 12 and 28 with or without recurrence, respectively, were retrospectively enrolled. Midstream urine samples were preoperatively collected. Urinary microbiota composition was analyzed by 16s rDNA sequencing. Alpha and beta diversities were measured. LEfSe analysis was employed to identify specific bacteria associated with recurrence. Intratumoral infiltration of FoxP3+ regulatory T cells and Ki-67 expression were evaluated by immunohistochemistry. Patients with recurrence had higher α-diversity compared to those without (Shannon Index, P = 0.0007, Simpson Index, P = 0.0004). Distinct beta diversity was observed between recurrence and non-recurrence groups (weighted Unifrac P = 0.02; unweighted Unifrac P = 0.001). LEfSe analysis showed that the recurrence group displayed marked enrichment of Pseudomonas, Staphylococcus, Corynebacterium, and Acinetobacter genera. Patients with higher alpha diversity had elevated Ki-67 expression than those with lower alpha diversity (P = 0.0194), although microbial diversity was unassociated with infiltration of FoxP3+ regulatory T cells (P = 0.1653). Patients with lower urinary microbial diversity had prolonged recurrence-free survival compared to those with higher diversity. Perturbation of urinary microbiota may induce immune evasion and tumor growth, eventually contributing to unfavorable outcomes. Additional study is warranted to confirm a causal role of urinary microbiota in modulating antitumor immune response and survival in bladder cancer.

6.
Int Immunopharmacol ; 103: 108445, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34998273

RESUMO

Chronic obstructive pulmonary disease (COPD) is characterized by increased cellular stress and inflammation. Heat shock protein 60 (HSP60) is a highly conserved stress protein that acts as a cellular "danger" signal for immune reactions. In this study, we investigated the role of HSP60 in COPD and explored the underlying mechanisms. Expression levels of HSP60 in patients with acute exacerbation of COPD (AECOPD), stable COPD, and healthy people were detected by Western blotting and enzyme-linked immunosorbent assay (ELISA). Moreover, the effect and molecular mechanism of HSP60 in COPD were studied in cigarette smoke (CS)-treated C57BL/6 mice and macrophages. The results showed significant upregulation of HSP60 expression in the peripheral blood mononuclear cells (PBMCs) and sera of patients with AECOPD compared to those with stable COPD or healthy people. CS induced the expression of HSP60 in the COPD mouse model, accelerated the activation of toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3) signalling pathways, promoted the increase of inflammatory cells in alveolar lavage fluid and serum inflammatory factors, and induced destruction of lung tissue structure. Furthermore, HSP60 knockdown affected TLR4 and MyD88 expression, IκBα degradation, and nuclear localization of NF-κB and NLRP3 inflammasome activity. Our study revealed that CS stimulates the expression of HSP60, activating the TLR4-MyD88-NF-κB signalling pathway and the NLRP3 inflammasome.

7.
J Minim Access Surg ; 18(1): 12-19, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35017392

RESUMO

Purpose: Considerable debates exist regarding the preferable technique to repair a paediatric inguinal hernia (PIH). This systematic review aims to compare the efficacy and safety of laparoscopic herniorrhaphy (LH) and open herniorrhaphy (OH) in PIH. Methods: The randomised controlled trials (RCTs) that compared the outcomes of LH and OH in PIH without region and language restrictions searched from the following databases: PubMed, Web of Science Database, Cochrane Library, SciELO Citation Index, Russian Science Citation Index, China National Knowledge Infrastructure, WanFang Data and China Science and Technology Journal Database. Results: A total of 13 RCTs that involving 1207 patients included in the review. The LH displayed a shorter operative time for bilateral hernia repair (weighted mean difference = -8.23, 95% confidence interval [CI]: -11.22~-5.23, P < 0.00001), a lower complication rate (odds ratio [OR] = 0.32, 95% CI: 013-0.83, P = 0.02) along with a lower wound infection (OR = 0.14, 95% CI: 0.04-0.55, P = 0.005) and major male-specific post-operative complications (OR = 0.10, 95% CI: 0.04-0.24, P < 0.00001) and a less contralateral metachronous inguinal hernia (CMIH) incidence rate (OR = 0.09, 95% CI: 0.02-0.42, P = 0.002). No significant difference was found for unilateral operative time, time to full recovery, length of hospital stay, recurrence and hydrocele rates between the two techniques. Conclusion: The present review reiterates that both the LH and OH techniques for the PIH repair are comparable. However, in some aspects, the LH is superior to the OH in terms of operative time for bilateral hernias, post-operative complications rate and CMIH incidence rate. Rigorously designed RCTs are anticipated to confirm the clinical effects of both LH and OH.

8.
Adv Sci (Weinh) ; : e2103303, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018740

RESUMO

Innate lymphoid cells (ILCs) are crucial in orchestrating immunity and maintaining tissue homeostasis in various barrier tissues, but whether ILCs influence immune responses in the urinary tract remains poorly understood. Here, bladder-resident ILCs are comprehensively explored and identified their unique phenotypic and developmental characteristics. Notably, bladder-resident ILCs rapidly respond to uropathogenic Escherichia coli (UPEC) infection. It is found that ILC3 is necessary for early protection against UPEC infection in the bladder. Mechanistically, UPEC infection leads to interleukin (IL)-1ß production in the bladder via a MyD88-dependent pathway, which promotes ILC3 activation. ILC3-expressed IL-17A further recruits neutrophils and controls UPEC infection in the bladder. Together, these results demonstrate a critical role for bladder ILCs in the host defense against UPEC infection.

9.
J Am Chem Soc ; 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034454

RESUMO

Native chemical ligation (NCL) provides a powerful solution to assemble proteins with precise chemical features, which enables a detailed investigation of the protein structure-function relationship. As an extension to NCL, the discovery of desulfurization and expressed protein ligation (EPL) techniques has greatly expanded the efficient access to large or challenging protein sequences via chemical ligations. Despite its superior reliability, the NCL-desulfurization protocol requires orthogonal protection strategies to allow selective desulfurization in the presence of native Cys, which is crucial to its synthetic application. In contrast to traditional thiol protecting groups, photolabile protecting groups (PPGs), which are removed upon irradiation, simplify protein assembly and therefore provide minimal perturbation to the peptide scaffold. However, current PPG strategies are mainly limited to nitro-benzyl derivatives, which are incompatible with NCL-desulfurization. Herein, we present for the first time that quinoline-based PPG for cysteine can facilitate various ligation strategies, including iterative NCL and EPL-desulfurization methods. 7-(Piperazin-1-yl)-2-(methyl)quinolinyl (PPZQ) caging of multiple cysteine residues within the protein sequence can be readily introduced via late-stage modification, while the traceless removal of PPZQ is highly efficient via photolysis in an aqueous buffer. In addition, the PPZQ group is compatible with radical desulfurization. The efficiency of this strategy has been highlighted by the synthesis of γ-synuclein and phosphorylated cystatin-S via one-pot iterative ligation and EPL-desulfurization methods. Besides, successful sextuple protection and deprotection of the expressed Interleukin-34 fragment demonstrate the great potential of this strategy in protein caging/uncaging investigations.

10.
Anim Biosci ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34991212

RESUMO

Objective: This study aimed to investigate the fermentation profiles, bacterial community and predicted metabolic characteristics of Sudangrass (Sorghum sudanense Stapf.) during ensiling. Methods: First-cutting Sudangrass was harvested at the vegetative stage and ensiled in laboratory-scale silos (1 L capacity). Triplicate silos were sampled after 1, 3, 7, 15, 30 and 60 days of ensiling, respectively. The bacterial communities on day 3 and 60 were assessed through high-throughput sequencing technology, and 16S rRNA-gene predicted functional profiles were analyzed according to the KEGG using Tax4Fun. Results: The Sudangrass silages showed good fermentation quality, indicated by higher lactic acid contents, and lower pH, butyric acid and ammonia nitrogen contents. The dominant genus Lactococcus on day 3 was replaced by Lactobacillus on day 60. The metabolism of amino acid, energy, cofactors and vitamins was restricted, and metabolism of nucleotide and carbohydrate was promoted after ensiling. The 1-phosphofructokinase and pyruvate kinase of bacterial community seemed to play important roles in stimulating the lactic acid fermentation, and the promotion of arginine deiminase could help lactic acid bacteria to tolerate the acidic environment. Conclusion: High-throughput sequencing technology combined with 16S rRNA gene-predicted functional analyses revealed the differences during the early and late stages of Sudangrass ensiling not only for distinct bacterial community but also for specific functional metabolites. The results could provide a comprehensive insight into bacterial community and metabolic characteristics to further improve the silage quality.

11.
BMC Microbiol ; 22(1): 7, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983384

RESUMO

BACKGROUND: Urogenital microbiota may be associated with the recurrence of bladder cancer, but the underlying mechanism remains unclear. The notion that microbiota can upregulate PD-L1 expression in certain epithelial tumors to promote immune escape has been demonstrated. Thus, we hypothesized that the urogenital microbiota may be involved in the recurrence and progression of non-muscle invasive bladder cancer (NMIBC) by upregulating the PD-L1 expression. To test this hypothesis, we investigated the relationship between urogenital microbial community and PD-L1 expression in male patients with NMIBC. RESULTS: 16S rRNA gene sequencing was performed to analyse the composition of urogenital microbiota, and the expression of PD-L1 in cancerous tissues was detected by immunohistochemistry. The subjects (aged 43-79 years) were divided into PD-L1-positive group (Group P, n = 9) and PD-L1-negative group (Group N, n = 19) respectively based on their PD-L1 immunohistochemical results. No statistically significant differences were found in the demographic characteristics between group P and N. We observed that group P exhibited higher species richness (based on Observed species and Ace index, both P < 0.05). Furthermore, subgroup analysis showed that the increase in number of PD-L1 positive cells was accompanied by increased richness of urogenital microbiota. Significantly different composition of urogenital microbiota was found between group P and group N (based on weighted Unifrac and unweighted Unifrac distances metric, both P < 0.05). Enrichment of some bacterial genera (e.g., Leptotrichia, Roseomonas, and Propionibacterium) and decrease of some bacterial genera (e.g., Prevotella and Massilia) were observed in group P as compared with group N. These findings indicated that these genera may affect the expression of PD-L1 through some mechanisms to be studied. CONCLUSION: Our study provided for the first time an overview of the association between urogenital microbiota and PD-L1 expression in male patients with NMIBC, indicating that urogenital microbiota was an important determinant of PD-L1 expression in male NMIBC patients.

12.
Mol Biol Rep ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981336

RESUMO

BACKGROUND: Stroke is the leading cause of disability and the third leading cause of death in the world, and no effective treatment has been developed. Oxidative stress-induced cell injury and genomic instability is implicated in the pathogenesis of stroke, whose prognosis remains poor. METHODS: A model of cerebral ischemic/reperfusion injury model was established through four artery occlusions. This study was carried out using western blot, flow cytometry and RT-PCR on cell line U251-MG. The cytotoxic effect of H2O2 and expression of LDH, caspase-3, MDA and SOD was analyzed by assay kit. RESULTS: We found that the expression of WDR26 was induced in cerebral ischemia-reperfusion injury in vivo and the expression of WDR26 was induced by H2O2 in a dose- and time-dependent manner in vitro. WDR26 over-expression significantly suppressed H2O2-induced cell death and caspase-3-mediated apoptosis in U251-MG cells. In contrast, inhibition of WDR26 markedly enhanced cell death in U251-MG cells. In addition, WDR26 regulated oxidative stress response and induced Nrf2/HO-1 pathway. CONCLUSIONS: These findings suggest that WDR26 mediates H2O2-induced oxidative stress and cell injury, possibly by reducing the intrinsic apoptotic pathway and activating Nrf2 and HO-1 in astrocytes.

13.
Inorg Chem ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35049281

RESUMO

Two bis-bis(urea) ligands (L1 and L2) incorporating the photoactive 9,10-diphenylanthracene fragment were designed for the construction of anion-coordination-driven assemblies and subsequent oxygenation of anthracene moieties for singlet oxygen storage. The corresponding A2L2-type sulfate complexes [TEA]4[(SO4)2(L1)2] (1) and [TEA]4[(SO4)2(L2)2] (2), where TEA = tetraethylammonium, were achieved by coordinating the ligands L1 or L2 with sulfate anions. Both 1 and 2 were able to undergo [4 + 2] photooxygenation to form endoperoxide photoproducts 1-EPO and 2-EPO, which can be partially converted back to the original anthracene compounds after heating. The structures of 1-EPO and 2-EPO were unambiguously confirmed by X-ray crystallography, NMR and UV-vis spectroscopy, and high-resolution electrospray ionization mass spectrometry.

14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 114-120, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35048610

RESUMO

Objective: To examine the performance and application value of improved Unet network technology in the recognition and segmentation of hemorrhage regions in brain CT images. Methods: A total of 476 brain CT images of patients with spontaneous intracerebral hemorrhage (SICH) were retrospectively included. The improved Unet network was used to identify and segment the hemorrhage regions in the patients' brain CT images. The CT imaging data of the hemorrhage regions were manually labelled by clinicians. After randomized sorting, 430 data sets from 106 patients were selected for inclusion in the training set and 46 data sets from 11 patients were included in the test set. After data enhancement, the experimental data set underwent network training and model testing in order to assess the segmentation performance. The segmentation results were compared with the those of the Unet network (Base), FCN-8s network and Unet++ network. Results: In the segmentation of brain CT image hemorrhage region with the improved Unet network, the three evaluation indicators of Dice similarity coefficient, positive predictive value (PPV), and sensitivity coefficient (SC) reached 0.8738, 0.9011 and 0.8648, respectively, increasing by 8.80%, 7.14% and 8.96%, respectively, compared with those of FCN-8s, and increasing by 4.56%, 4.44% and 4.15%, respectively, compared with those of Unet network (Base). The improved Unet network also showed better segmentation performance than that of Unet++ network. Conclusion: The improved method based on Unet network proposed in this report displayed good performance in the recognition and segmentation of hemorrhage regions in brain CT images, and is an appropriate method for the recognition and segmentation of hemorrhage regions in brain CT images, showing potential application value for assisting clinical decision-making and preventing early hematoma expansion.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Encéfalo/diagnóstico por imagem , Hemorragia , Humanos , Estudos Retrospectivos
15.
Mar Drugs ; 20(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35049903

RESUMO

Although the S8 family in the MEROPS database contains many peptidases, only a few S8 peptidases have been applied in the preparation of bioactive oligopeptides. Bovine bone collagen is a good source for preparing collagen oligopeptides, but has been so far rarely applied in collagen peptide preparation. Here, we characterized a novel S8 gelatinase, Aa2_1884, from marine bacterium Flocculibacter collagenilyticus SM1988T, and evaluated its potential application in the preparation of collagen oligopeptides from bovine bone collagen. Aa2_1884 is a multimodular S8 peptidase with a distinct domain architecture from other reported peptidases. The recombinant Aa2_1884 over-expressed in Escherichia coli showed high activity toward gelatin and denatured collagens, but no activity toward natural collagens, indicating that Aa2_1884 is a gelatinase. To evaluate the potential of Aa2_1884 in the preparation of collagen oligopeptides from bovine bone collagen, three enzymatic hydrolysis parameters, hydrolysis temperature, hydrolysis time and enzyme-substrate ratio (E/S), were optimized by single factor experiments, and the optimal hydrolysis conditions were determined to be reaction at 60 ℃ for 3 h with an E/S of 400 U/g. Under these conditions, the hydrolysis efficiency of bovine bone collagen by Aa2_1884 reached 95.3%. The resultant hydrolysate contained 97.8% peptides, in which peptides with a molecular weight lower than 1000 Da and 500 Da accounted for 55.1% and 39.5%, respectively, indicating that the hydrolysate was rich in oligopeptides. These results indicate that Aa2_1884 likely has a promising potential application in the preparation of collagen oligopeptide-rich hydrolysate from bovine bone collagen, which may provide a feasible way for the high-value utilization of bovine bone collagen.

16.
J Sci Food Agric ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044686

RESUMO

BACKGROUND: To study the contributions of chemical and microbial diurnal variations in fermentation characteristics and bacterial community of Napier grass silage, gamma-ray irradiated Napier grass harvested at 7:00 (AM), 12:00 (M) and 17:00 (PM) was inoculated with the microbiota derived from Napier grass harvested at AM, M and PM in a 3 (irradiated forage: AMG , MG and PMG ) × 3 (microbiota: AMM , MM and PMM ) design and then ensiled for 14 and 60 days. RESULTS: Napier grass harvested at various times had different chemical composition and epiphytic microbiota prior to ensiling. For silages inoculated with the same microbiota, the pH values, residual WSC and DM contents increased and lactic acid, acetic acid, propionic acid, butyric acid, ethanol and VFA contents decreased in PMG and MG silages compared with AMG silages. MM and PMM inoculum promoted lactic acid fermentation indicated by lower pH values throughout the ensiling and higher lactic acid contents plus lactic/acetic acid ratio on d 60 compared with those in AMM -inoculated silages. During ensiling, epiphytic microbiota affected the Chao1 and OTUs number and Shannon indices as well as the abundances of more than half of the top 10 abundant genera, while chemical composition did not affect any of the bacterial diversity and richness indices and only showed significant impacts on the abundances of two genera. CONCLUSION: Chemical diurnal variation exerted an influence mainly on the extent of fermentation, whereas microbial diurnal variation affected more on the bacterial community and fermentation types during Napier grass ensiling. This article is protected by copyright. All rights reserved.

17.
Exp Cell Res ; 411(2): 113017, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34998813

RESUMO

Hypertensive renal injury is accompanied by tubular interstitial fibrosis leading to increased risk for renal failure. This study aimed to explore the influences of miR-122-5p in hypertension-mediated renal fibrosis and damage. 14-week-old male SHR and WKY rats were randomly assigned to treat with rAAV-miR-122-5p or rAAV-GFP for 8 weeks. There were marked increases in miR-122-5p and Kim-1 levels and decreases in FOXO3 and SIRT6 levels in hypertensive rats. Transfection with rAAV-miR-122-5p triggered exacerbation of renal fibrosis, apoptosis and inflammatory injury in SHR, associated with downregulated levels of FOXO3, SIRT6, ATG5 and BNIP3 as well as upregulated expression of Kim-1, NOX4, CTGF, and TGF-ß1. In cultured primary mouse renal tubular interstitial fibroblasts, exposure to angiotensin II resulted in obvious downregulation of FOXO3, SIRT6, ATG5, BNIP3 and nitric oxide levels as well as augmented cellular migration, oxidative stress, and inflammation, which were exacerbated by miR-122-5p mimic while rescued by miR-122-5p inhibitor and rhFOXO3, respectively. Notably, knockdown of FOXO3 strikingly blunted cellular protective effects of miR-122-5p inhibitor. In summary, miR-122-5p augments renal fibrosis, inflammatory and oxidant injury in hypertensive rats by suppressing the expression of FOXO3. Pharmacological inhibition of miR-122-5p has potential therapeutic significance for hypertensive renal injury and fibrosis-related kidney diseases.

18.
Theranostics ; 12(2): 976-998, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976224

RESUMO

Rationale: We found that a subset of signal transducer and activator of transcription 3 (STAT3) translocated into mitochondria in phagocytes, including macrophages isolated from individuals with sepsis. However, the role of mitochondrial STAT3 in macrophages remains unclear. Method: To investigate the function of mitochondrial STAT3 in vivo, we generated inducible mitochondrial STAT3 knock-in mice. A cytokine array analysis, a CBA analysis, flow cytometry, immunofluorescence staining and quantification and metabolic analyses in vivo were subsequently performed in an LPS-induced sepsis model. Single-cell RNA sequencing, a microarray analysis, metabolic assays, mass spectrometry and ChIP assays were utilized to gain insight into the mechanisms of mitochondrial STAT3 in metabolic reprogramming in LPS-induced sepsis. Results: We found that mitochondrial STAT3 induced NF-κB nuclear localization and exacerbated LPS-induced sepsis in parallel with a metabolic switch from mainly using glucose to an increased reliance on fatty acid oxidation (FAO). Moreover, mitochondrial STAT3 abrogated carnitine palmitoyl transferase 1a (CPT1a) ubiquitination and degradation in LPS-treated macrophages. Meanwhile, an interaction between CPT1a and ubiquitin-specific peptidase 50 (USP50) was observed. In contrast, knocking down USP50 decreased CPT1a expression and FAO mediated by mitochondrial STAT3. The ChIP assays revealed that NF-κB bound the USP50 promoter. Curcumin alleviated LPS-mediated sepsis by suppressing the activities of mitochondrial STAT3 and NF-κB. Conclusion: Our findings reveal that mitochondrial STAT3 could trigger FAO by inducing CPT1a stabilization mediated by USP50 in macrophages, at least partially.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34989966

RESUMO

Poly-γ-glutamic acid (γ-PGA) is an important biopolymer with many applications due to its biodegradable and non-toxic characteristics. γ-PGA is produced industrially by fermentation of Bacillus species. The optimal pH range for producing γ-PGA by Bacillus subtilis PG-001 was firstly studied by glucose fed-batch fermentation with non-controlled pH. Result showed that both cell growth and γ-PGA synthesis were repressed when pH was lower than pH 6. Further investigation with γ-PGA fed-batch fermentation showed that pH 6.5 is more suitable for γ-PGA fermentation than pH 7. Under comparable consumption of glutamic acid and glucose, 11.8 g/L γ-PGA and 0.7 g/g yield were achieved by fermentation at pH 6.5, which was significantly higher than 10.5 g/L and 0.56 g/g yield of fermentation at pH 7. In addition, γ-PGA degradation during later phase of fermentation was repressed at pH 6.5 as 9238cP of final broth viscosity was achieved from fermentation at pH 6.5 while it was only 346 cP for fermentation at pH 7. Finally, a glucose feedback control pH-stat strategy was performed for reducing alkali consumption during γ-PGA fermentation, which further increased final γ-PGA concentration to 15.5 g/L with much higher viscosity (11458 cP); meanwhile the consumption of alkali decreased 57%. The fed-batch γ-PGA fermentation with glucose feedback control pH-stat strategy showed high feasibility for industrial scaling-up.

20.
Mol Med Rep ; 25(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35059738

RESUMO

The present study explored the protective effect of exogenous hydrogen sulfide (H2S) on lipopolysaccharide (LPS)­induced acute kidney injury (AKI) and the underlying mechanisms. To establish an AKI injury mouse model, LPS (10 mg/kg) was intraperitoneally injected into mice pretreated with 0.8 mg/kg sodium hydrosulfide hydrate (NaHS), an H2S donor. The mouse survival rate and the degree of kidney injury were examined. To construct a cell damage model, HK­2 cells were pretreated with different concentrations (0.1, 0.3 and 0.5 mM) of NaHS, and then the cells were stimulated with LPS (1 µg/ml). The cell viability, autophagy, apoptosis levels and the release of inflammatory factors were examined in mouse kidney tissue and HK­2 renal tubular epithelial cells. It was found that pretreatment with NaHS significantly improved the survival rate of septic AKI mice, and reduced the renal damage, release of inflammatory factors and apoptosis. In HK­2 cells, NaHS protected cells from LPS caused damage via promoting autophagy and inhibiting apoptosis and the release of inflammatory factors. In order to clarify the relationship between autophagy and apoptosis and inflammatory factors, this study used 3­methyladenine (3­MA) to inhibit autophagy. The results revealed that 3­MA eliminated the protective effect of NaHS in HK­2 cells and AKI mice. Overall, NaHS can protect from LPS­induced AKI by promoting autophagy and inhibiting apoptosis and the release of inflammatory factors.

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