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1.
Microb Biotechnol ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604311

RESUMO

In addition to being an important intermediate in the TCA cycle, L-malate is also widely used in the chemical and beverage industries. Due to the resulting high demand, numerous studies investigated chemical methods to synthesize L-malate from petrochemical resources, but such approaches are hampered by complex downstream processing and environmental pollution. Accordingly, there is an urgent need to develop microbial methods for environmentally-friendly and economical L-malate biosynthesis. The rapid progress and understanding of DNA manipulation, cell physiology, and cell metabolism can improve industrial L-malate biosynthesis by applying intelligent biochemical strategies and advanced synthetic biology tools. In this paper, we mainly focused on biotechnological approaches for enhancing L-malate synthesis, encompassing the microbial chassis, substrate utilization, synthesis pathway, fermentation regulation, and industrial application. This review emphasizes the application of novel metabolic engineering strategies and synthetic biology tools combined with a deep understanding of microbial physiology to improve industrial L-malate biosynthesis in the future.

2.
J Med Virol ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36606607

RESUMO

Global COVID-19 pandemics highlight the need of developing vaccines with universal and durable protection against emerging SARS-CoV-2 variants. Here we developed an extended-release vaccine delivery system (GP-diABZI-RBD), consisting the original SARS-CoV-2 WA1 strain receptor-binding domain (RBD) as the antigen and diABZI STING agonist in conjunction with yeast ß-glucan particles (GP-diABZI) as the platform. GP-diABZI-RBD could activate STING pathway and inhibit SARS-CoV-2 replication. Compared to diABZI-RBD, intraperitoneal injection of GP-diABZI-RBD elicited robust cellular and humoral immune responses in mice. Using SARS-CoV-2 GFP/ΔN transcription and replication-competent virus-like particle system (trVLP), we demonstrated that GP-diABZI-RBD-prototype vaccine exhibited the strongest and durable humoral immune responses and antiviral protection; whereas GP-diABZI-RBD-Omicron displayed minimum neutralization responses against trVLP. By using pseudotype virus (PsVs) neutralization assay, we found that GP-diABZI-RBD-Prototype, GP-diABZI-RBD-Delta, and GP-diABZI-RBD-Gamma immunized mice sera could efficiently neutralize Delta and Gamma PsVs, but had weak protection against Omicron PsVs. In contrast, GP-diABZI-RBD-Omicron immunized mice sera displayed the strongest neutralization response to Omicron PsVs. Taken Together, the results suggest that GP-diABZI can serve as a promising vaccine delivery system for enhancing durable humoral and cellular immunity against broad SARS-CoV-2 variants. Our study provides important scientific basis for developing SARS-COV-2 VOC-specific vaccines. This article is protected by copyright. All rights reserved.

3.
ACS Biomater Sci Eng ; 9(1): 437-448, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36508691

RESUMO

Local causes of slow wound healing include infection and wound hemorrhage. Using sodium bicarbonate as a neutralizer, a variety of carboxymethyl chitosan-tannic acid (CMC-TA) composite hydrogels solidify through hydrogen bonding in this study. The best-performing hydrogel was synthesized by altering the concentration of TA and exhibited remarkable mechanical properties and biocompatibility. Following in vitro characterization tests, the CMC-TA hydrogel exhibited remarkable antibacterial and antioxidant properties, as well as quick hemostasis capabilities. In the in vivo wound healing study, the results showed that the CMC-TA hydrogel could relieve inflammation and promote the recovery of skin incision, re-epithelialization, and collagen deposition. Overall, this multifunctional hydrogel could be an ideal wound dressing for the clinical therapy of full-thickness wounds.


Assuntos
Quitosana , Quitosana/farmacologia , Hidrogéis/farmacologia , Antioxidantes/farmacologia , Cicatrização , Antibacterianos/farmacologia , Hemostasia
5.
Nanomaterials (Basel) ; 12(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36558330

RESUMO

Just-in-time evaluation of drug resistance in situ will greatly facilitate the achievement of precision cancer therapy. The rapid elevation of reactive oxygen species (ROS) is the key to chemotherapy. Hence, suppressed ROS production is an important marker for chemotherapy drug resistance. Herein, a NIR-II emission smart nanoprobe (LnNP@ZIF8, consisting of a lanthanide-doped nanoparticle (LnNP) core and metal-organic framework shell (ZIF8)) is constructed for drug delivery and in vivo NIR-II ratiometric imaging of ROS for tumor drug resistance evaluation. The drug-loaded nanoprobes release therapeutic substances for chemotherapy in the acidic tumor tissue. As the level of ROS increases, the LnNPs shows responsively descending fluorescence intensity at 1550 nm excited by 980 nm (F1550, 980Ex), while the fluorescence of the LnNPs at 1060 nm excited by 808 nm (F1060, 808Ex) is stable. Due to the ratiometric F1550, 980Ex/F1060, 808Ex value exhibiting a linear relationship with ROS concentration, NIR-II imaging results of ROS change based on this ratio can be an important basis for determining tumor drug resistance. As the chemotherapy and resistance evaluation are explored continuously in situ, the ratiometric imaging identifies drug resistance successfully within 24 h, which can greatly improve the timeliness of accurate treatment.

6.
Front Psychiatry ; 13: 997174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440399

RESUMO

Objective: To investigate the adaptability of Comprehensive Behavioral Intervention for Tics (CBIT) for a Chinese population, and evaluate the efficacy of combined CBIT and pharmacotherapy (CBIT + PT) compared to CBIT or pharmacotherapy (PT) alone for reducing tics and for improving the quality of life (QoL) in a sample of Chinese children with chronic tic disorders (CTD) and Tourette syndrome (TS). Materials and methods: In this 10-week randomized controlled pilot trial, 37 outpatients aged between 6 and 16 years affected by TS and CTD were randomly assigned to receive CBIT (n = 22) or PT alone (n = 15). Considering the feasibility, the patients allocated to the CBIT treatment group could further choose whether to simultaneously take medicine voluntarily, resulting in a CBIT alone group (n = 12) and a CBIT + PT group (n = 10). Results: At baseline, no significant difference was found between the three groups in the demographic and clinical characteristics (p > 0.05). All three groups showed a significant reduction in tic severity after treatment assessed by the Yale Global Tic Severity Scale (YGTSS) severity score [F (2,33) = 35.05, p < 0.001, η p 2 = 0.51], the score of the Clinical Global Impression scale for Improvement (CGI-I) [F (1,34) = 13.87, p = 0.001, η p 2 = 0.29], and YGTSS impairment score [F (2,33) = 31.71, p < 0.001, η p 2 = 0.48]. Significant interactions were found between the time-point and group in emotional functioning [F (2,29) = 4.39, p = 0.02, η p 2 = 0.23], psychosocial functioning [F (2,29) = 5.93, p = 0.007, η p 2 = 0.29], and total QoL score [F (1,34) = 3.72, p = 0.04, η p 2 = 0.20] of Pediatric Quality of Life Inventory (PedsQL 4.0) for children suggesting a significantly larger improvement in emotional functioning, psychosocial functioning, and total QoL score of the life quality in the CBIT group for children self-report. PedsQL for proxy report only showed a significant main effect of time-point in physical functioning [F (1,33) = 8.35, p = 0.01, η p 2 = 0.2], emotional functioning [F (1,33) = 10.75, p = 0.002, η p 2 = 0.25], psychosocial functioning [F (1,34) = 11.38, p = 0.002, η p 2 = 0.26], and total Qol score [F (1,34) = 13.21, p = 0.001, η p 2 = 0.29]. Conclusion: CBIT is probably effective in reducing tic severity in Chinese children with tic disorders. CBIT + PT may not be superior to CBIT alone in reducing tic severity and improving quality of life. CBIT alone showed advantages in improving quality of life over CBIT + PT and PT alone. CBIT might be an appropriate treatment option for patients with tic disorder in Chinese mainland.

7.
Front Comput Neurosci ; 16: 1047954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405786

RESUMO

Tic is a combination of a series of static facial and limb movements over a certain period in some children. However, due to the scarcity of tic disorder (TD) datasets, the existing work on tic recognition using deep learning does not work well. It is that spatial complexity and time-domain variability directly affect the accuracy of tic recognition. How to extract effective visual information for temporal and spatial expression and classification of tic movement is the key of tic recognition. We designed the slow-fast and light-efficient channel attention network (SFLCA-Net) to identify tic action. The whole network adopted two fast and slow branch subnetworks, and light-efficient channel attention (LCA) module, which was designed to solve the problem of insufficient complementarity of spatial-temporal channel information. The SFLCA-Net is verified on our TD dataset and the experimental results demonstrate the effectiveness of our method.

8.
J Med Virol ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401153

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants have caused hundreds of thousands of deaths and shown serious social influence worldwide. Jilin Province, China, experienced the first wave of the outbreak from December 2020 to February 2021. Here, we analysed the genomic characteristics of the SARS-CoV-2 outbreak in Jilin province using a phylogeographic tree and found that clinical isolates belonged to the B.1 lineage, which was considered to be the ancestral lineage. Several dominant SARS-CoV-2 specific linear B cell epitopes that reacted with the convalescent sera were also analysed and identified using a peptide microarray composed of S, M, and E proteins. Moreover, the serum of convalescent patients infected with SARS-CoV-2 showed neutralising activity against four widely spreading SARS-CoV-2 variants; however, significant differences were observed in neutralising activities against different SARS-CoV-2 variants. These data provide important information on genomic characteristics, linear epitopes, and neutralising activity of SARS-CoV-2 outbreak in Jilin Province, China, which may aid in understanding disease patterns and regional aspects of the pandemic. This article is protected by copyright. All rights reserved.

9.
Sci Rep ; 12(1): 18807, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335239

RESUMO

More and more evidence show that HK2 is closely related to tumors. But no pan-cancer analysis is available. This paper aimed to explore the potential roles of HK2 across thirty-three tumors based on the datasets of the cancer genome Atlas (TCGA) and gene expression omnibus. HK2 is highly expressed in most tumors and related to the progression of some tumors. HK2 expression was associated with the infiltration of T follicular helper cells for the TCGA tumors of uveal melanoma, breast invasive carcinoma (BRCA), breast invasive carcinoma-luminalA (BRCA-LumA), head and neck squamous cell carcinoma (HNSC), head and neck squamous cell carcinoma with HPV positive (HNSC-HPV+), and cancer-associated fibroblasts for the tumors of brain lower grade glioma and stomach adenocarcinoma. Our first pan-cancer study offers a relatively comprehensive understanding of the roles of HK2 in different tumors.


Assuntos
Neoplasias da Mama , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Feminino , Hexoquinase/genética , Hexoquinase/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Neoplasias da Mama/genética
10.
Nat Commun ; 13(1): 7323, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443308

RESUMO

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.


Assuntos
Anticorpos Neutralizantes , Resistência à Insulina , Humanos , Camundongos , Animais , Dieta , Obesidade/genética , Obesidade/prevenção & controle , Transporte Biológico , Camundongos Obesos , Proteínas de Membrana
11.
Nutrients ; 14(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36432503

RESUMO

BACKGROUND: Non-puerperal mastitis (NPM), a recurrent chronic inflammation of non-lactating breast, often proves tremendous difficulty in treatment, and it may give rise to its complicated symptoms and unclear etiology. Furthermore, the clinical morbidity rate of NPM has been increasing in recent years. METHODS: Overall, 284 patients diagnosed with NPM were consecutively recruited as cases in this study, and patients with benign breast disease (n = 1128) were enrolled as control. The clinical, biomedical, and pathological indicators were analyzed. Univariate and multivariate logistic analysis were used to distinguish risks between NPM and benign breast mass patients. Furthermore, according to the pathological characteristics, the patients of NPM were classified into two subgroups: mammary duct ectasia (MDE) and granulomatous lobular mastitis (GLM). The differences of biomedical indicators between MDE and GLM groups were also analyzed. RESULTS: Compared with benign breast mass group, the level of high-density lipoprotein (HDL-C) significantly decreased, while lipoprotein(a) (Lp(a)) and blood glucose (GLU) both increased in NPM group. According to univariate and multivariate logistic analysis, the onset age and HDL-C were generally decreased, while Lp(a) and GLU were increased in NPM group. The onset age, HDL-C, Lp(a), and GLU were modeled to distinguish NPM and benign breast mass. Significant differences were also observed between MDE and GLM patients in biomedical indicators, such as lipoprotein(a) (Lp(a)), lactate dehydrogenase (LDH), creatine kinase (CK), total cholesterol (TC), and so on. CONCLUSIONS: Our results indicated for the first time that biomarkers were associated with NPM. The biomedical indicators involved in lipid metabolism might be important factors in the development and treatment of NPM. In addition, MDE and GLM are two diseases with different inflammatory states of NPM. These findings would be helpful for a better understanding of NPM and give us some insights to develop new diagnostic and therapeutic strategies.


Assuntos
Mastite , Feminino , Humanos , Estudos Retrospectivos , Mastite/diagnóstico , Inflamação , Lipoproteína(a) , Lipoproteínas HDL
12.
Int J Mol Sci ; 23(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36362094

RESUMO

Sirtuin 4 (SIRT4), a member of the SIRT family, has been reported to be a key factor involved in antioxidant defense in mitochondria. This study aimed to explore the potential molecular mechanism via which SIRT4 regulates heat stress-induced oxidative stress and lactoprotein synthesis in bovine mammary epithelial cells (BMECs). Our results showed that SIRT4 was significantly decreased in heat stressed mammary tissue. Depletion of SIRT4 in BMECs induced the generation of ROS, which, as exhibited by the decreased activity of antioxidant enzymes, changed mitochondrial morphology through mediating protein and mRNA levels related to mitochondrial fission and fusion. Moreover, we found that depletion of SIRT4 or stress conditions inhibited the expression of milk proteins, as well as lipid and glucose synthesis-related genes, and activated the AMPK/mTOR signaling pathway. Increased SIRT4 expression was found to have the opposite effect. However, blocking the AMPK/mTOR signaling pathway could inhibit the regulatory function of SIRT4 in milk synthesis-related gene expression. In summary, our results suggest that SIRT4 may play critical roles in maintaining mammary gland function by regulating the AMPK/mTOR signaling pathway in dairy cows, indicating that SIRT4 may be a potential molecular target for curing heat stress-induced BMEC injury and low milk production in dairy cows.


Assuntos
Proteínas Quinases Ativadas por AMP , Antioxidantes , Feminino , Bovinos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/farmacologia , Transdução de Sinais , Células Epiteliais/metabolismo , Resposta ao Choque Térmico , Serina-Treonina Quinases TOR/metabolismo , Glândulas Mamárias Animais/metabolismo
13.
Front Microbiol ; 13: 932294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312920

RESUMO

Abdominal irradiation (IR) destroys the intestinal mucosal barrier, leading to severe intestinal infection. There is an urgent need to find safe and effective treatments to reduce IR-induced intestinal injury. In this study, we reported that metformin protected mice from abdominal IR-induced intestinal injury by improving the composition and diversity of intestinal flora. The elimination of intestinal microbiota (Abx) abrogated the protective effects of metformin on irradiated mice. We further characterized that treatment of metformin increased the murine intestinal abundance of Lactobacillus, which mediated the radioprotective effect. The administration of Lactobacillus or fecal microbiota transplantation (FMT) into Abx mice considerably lessened IR-induced intestinal damage and restored the radioprotective function of metformin in Abx mice. In addition, applying the murine intestinal organoid model, we demonstrated that IR inhibited the formation of intestinal organoids, and metformin alone bore no protective effect on organoids after IR. However, a combination of metformin and Lactobacillus or Lactobacillus alone displayed a strong radioprotection on the organoid formation. We demonstrated that metformin/Lactobacillus activated the farnesoid X receptor (FXR) signaling in intestinal epithelial cells and hence upregulated tight junction proteins and mucins in intestinal epithelia, increased the number of goblet cells, and augmented the mucus layer thickness to maintain the integrity of intestinal epithelial barrier, which eventually contributed to reduced radiation intestinal injury. In addition, we found that Lactobacillus abundance was significantly increased in the intestine of patients receiving metformin while undergoing abdominal radiotherapy and the abundance was negatively correlated with the diarrhea duration of patients. In conclusion, our results demonstrate that metformin possesses a protective effect on IR-induced intestinal injury by upregulating the abundance of Lactobacillus in the intestine.

14.
Int J Biol Macromol ; 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36265533

RESUMO

The introduction of antibacterial and hemostatic hydrogels with good mechanical properties that display desirable impacts on wound healing process is still an unmet essential for clinical wound dressings. Herein, a multifunctional hydrogel PEG-CMC-THB-PRTM was fabricated via a one-pot method combining carboxymethyl chitosan (CMC), 2,3,4-trihydroxybenzaldehyde (THB), protamine (PRTM) and 4-arm polyethylene glycol aldehyde (PEG). The hydrogel was formed by the dynamic Schiff base reaction between amino groups of carboxymethyl chitosan and aldehyde groups of 4-arm polyethylene glycol aldehyde and exhibited excellent mechanical properties. The developed hydrogel also showed outstanding effects on anti-bacteria and hemostasis through the release of PRTM. Moreover, the hydrogel could promote extracellular matrix formation and wound closure in vivo, thereby accelerating the healing of skin wound. These results suggested that the multifunctional PEG-CMC-THB-PRTM hydrogel is a promising candidate for the clinical treatment of full-thickness wounds.

15.
Int Urol Nephrol ; 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253606

RESUMO

PURPOSE: To compare the efficacy and safety of optical puncture combined with standard percutaneous nephrolithotomy (PNL) and conventional PNL for the treatment of patients with complex kidney stones with no or mild hydronephrosis. METHODS: We retrospectively reviewed the data on patients with complex kidney stones treated by PNL in our hospital between May 2019 and February 2022. The patients were divided into two groups according to the puncture techniques applied. In the optical puncture group, 40 patients underwent optical puncture combined with standard PNL. In the control group, 44 patients underwent conventional standard PNL. The demographics and perioperative parameters were analyzed between the two groups. RESULTS: There mean puncture durations were significantly shorter in the optical puncture group (8.2 ± 2.16 min) than in the control group (14.0 ± 6.76 min) (P = 0.001). The re-puncture rates were lower in the optical puncture group (5%) compared with the control group (20.5%) (P = 0.036). The access loss rate in the optical puncture group (2.5%) was significantly lower than that in the control group (11.36%) (P = 0.037). The mean hemoglobin drop was significantly lower in the optical puncture group (12.6 ± 5.36 g/L) compared with the control group (22.3 ± 11.61 g/L) (P = 0.001). The mean hospital stay was significantly shorter in the optical puncture group (3.9 ± 1.65d) compared with the control group (5.1 ± 2.10d) (P = 0.042). The primary stone-free rate in the optical puncture group (87.5%) was similar to the control group (84.1%) (P = 0.656). The overall stone-free rates were 95% in the optical puncture group and 93.2% in the control group (P = 0.725). There were significantly more patients in the control group (18.2%) who suffered collecting system injury than in the optical puncture group (2.5%) (P = 0.020). There were no significant differences between the two groups in terms of blood transfusion (P = 0.292), fever (P = 0.696) and urosepsis (P = 0.946). CONCLUSION: We demonstrated that optical puncture combined with standard PNL could increase the precision and success rate of puncture, and reduce the access-related complications in patients with complex kidney stones without hydronephrosis.

16.
Neurooncol Adv ; 4(1): vdac131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225650

RESUMO

Background: Chromosomal translocation has been detected in many human cancers including gliomas and is considered a driving force in tumorigenesis. Co-deletion of chromosome arms 1p and 19q is a hallmark for oligodendrogliomas. On the molecular level, 1p/19q co-deletion results from t(1;19)(q10;p10), which leads to the concomitant formation of a hybrid chromosome containing the 1q and 19p arms. A method to generate 1p/19q co-deletion is lacking, which hinders the investigation of how 1p/19q co-deletion contributes to gliomagenesis. Methods: We hypothesized that chromosomal translocation, such as t(1;19)(q10;p10) resulting in the 1p/19q co-deletion, may be induced by simultaneously introducing DNA double-strand breaks (DSBs) into chromosomes 1p and 19q using CRISPR/Cas9. We developed a CRISPR/Cas9-based strategy to induce t(1;19)(q10;p10) and droplet digital PCR (ddPCR) assays to detect the hybrid 1q/19p and 1p/19q chromosomes. Results: After translocation induction, we detected both 1p/19q and 1q/19p hybrid chromosomes by PCR amplification of the junction regions in HEK 293T, and U-251 and LN-229 glioblastoma cells. Sequencing analyses of the PCR products confirmed DNA sequences matching both chromosomes 1 and 19. Furthermore, the 1p/19q hybrid chromosome was rapidly lost in all tested cell lines. The 1q/19p hybrid chromosome also become undetectable over time likely due to cell survival disadvantage. Conclusion: We demonstrated that t(1;19)(q10;p10) may be induced by CRISPR/Cas9-mediated genomic editing. This method represents an important step toward engineering the 1p/19q co-deletion to model oligodendrogliomas. This method may also be generalizable to engineering other cancer-relevant translocations, which may facilitate the understanding of translocation roles in cancer progression.

17.
Genes (Basel) ; 13(10)2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36292673

RESUMO

MicroRNAs (miRNAs) play key roles in sperm as the regulatory factors involved in fertility and subsequent early embryonic development. Bta-miR-6531 is specifically a highly enriched miRNA in low-motility sperms in previous study. To investigate the mechanism of bta-miR-6531, 508 shared target genes of bta-miR-6531 were predicted using two miRNA target databases (TargetScan7 and miRWalk). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), the calcium and cAMP signaling pathways were the most enriched of the target genes. A dual-luciferase assay indicated that bta-miR-6531 targeted ATP2A2 mRNA by binding to the coding sequence region. In bovine Leydig cells, bta-miR-6531 overexpression affected the intracellular calcium concentration by restraining ATP2A2 expression. Moreover, we observed high calcium concentrations and high ATP2A2 protein levels in high-motility sperm compared with those in low-motility sperms. Furthermore, high-linkage single-nucleotide polymorphisms (SNPs) of the pre-bta-miR-6531 sequence were identified that related to sperm traits. Genotype TCTC of bta-miR-6531 showed high sperm motility and density and low deformity rate in Holstein bulls. However, the mutation in pre-miR-6531 did not significantly affect mature bta-miR-6531 expression in the sperm or cell models. Our results demonstrate that bta-miR-6531 might involve in sperm motility regulation by targeting ATP2A2 of the calcium signaling pathway in bovine spermatozoa.


Assuntos
Cálcio , MicroRNAs , Bovinos , Masculino , Animais , Motilidade Espermática/genética , Células Intersticiais do Testículo/metabolismo , Sêmen/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro
19.
Int J Biol Macromol ; 222(Pt A): 1092-1100, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183755

RESUMO

The immunostimulatory activity of polysaccharides can improve human immunity, but their activity is low and prompting the activity is a great challenge. Curdlan, is a linear beta-1,3-glucan and has the potential to induce immune responses. However, owing to its tight triple helix structure and insolubility in water, its immunostimulatory activity is weakened. The keyway to promote its immunostimulatory activity is to relax its tight triple helix structure. In this work, methoxypolyethylene glycol (mPEG) was grafted onto curdlan (curdlan-g-mPEG) to unwind its triple helix structure. With its grafting mPEG, the water solubility of curdlan was enhanced. Moreover, with curdlan-g-mPEG treatment, macrophages secreted more tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 and exhibited favorable phagocytosis of bacteria (Staphylococcus aureus and Pseudomonas aeruginosa). These results reveal that curdlan-g-mPEG as an immunostimulant has potential applications in immunology and antibiotics.


Assuntos
beta-Glucanas , Humanos , beta-Glucanas/farmacologia , beta-Glucanas/química , Polietilenoglicóis , Interleucina-6 , Fator de Necrose Tumoral alfa , Água
20.
J Proteomics ; 268: 104715, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36058541

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent threat to human health. Major outer membrane proteins (OMPs) porin mutation is one important resistance mechanism of CRKP, and may also affect the inhibition activity of ß-lactam and ß-lactamase inhibitor combinations. The ertapenem-resistant K. pneumoniae strain 2018B120 with major porin mutations was isolated from a clinical patient. Genomic and time-series proteomic analyses were conducted to retrieve the ertapenem-challenged response of 2018B120. The abundance changing of proteins from PTS systems,  ABC transporters, the autoinducer 2 (AI-2) quorum sensing system, and antioxidant systems can be observed. Overexpression of alternative porins was also noticed to balance major porins' defection. These findings added a detailed regulation network in bacterial resistance mechanisms and gave new insights into bypass adaptation mechanisms the porin deficient bacteria adopted under carbapenem antibiotics pressure. SIGNIFICANCE: Outer membrane porins deficiency is an important mechanism of carbapenem resistance in K. pneumoniae. Comprehensive genomic and proteomic profiling of an ertapenem-resistant K. pneumoniae strain 2018B120 gives a detailed systematic regulation network in bacterial resistance mechanisms. Overexpression of alternative porins to balance major porins' defection was noticed, giving new insights into bypass adaptation mechanisms of porin deficient bacteria.


Assuntos
Klebsiella pneumoniae , Porinas , Resistência beta-Lactâmica , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antibacterianos/farmacologia , Antioxidantes/metabolismo , Proteínas de Bactérias/metabolismo , Carbapenêmicos/metabolismo , Carbapenêmicos/farmacologia , Ertapenem/metabolismo , Ertapenem/farmacologia , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Porinas/genética , Porinas/metabolismo , Proteômica/métodos , Resistência beta-Lactâmica/genética , Inibidores de beta-Lactamases/metabolismo , beta-Lactamases/genética , beta-Lactamases/metabolismo , beta-Lactamas/metabolismo , beta-Lactamas/farmacologia
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