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1.
J Hazard Mater ; 442: 130034, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36206716

RESUMO

The toxicity of nanoplastics (NPs) at relatively low concentrations to soil fauna at different organismal levels is poorly understood. We investigated the responses of earthworm (Eisenia fetida) to polystyrene NPs (90-110 nm) contaminated soil at a relatively low concentration (0.02 % w:w) based on multi-omics, morphological, and intestinal microorganism analyses. Results showed that NPs accumulated in earthworms' intestinal tissues. The NPs damaged earthworms' digestive and immune systems based on injuries of the intestinal epithelium and chloragogenous tissues (tissue level) and increased the number of changed genes in the digestive and immune systems (transcriptome level). The NPs reduced gut microorganisms' diversity (Shannon index) and species richness (Chao 1 index). Proteomic, transcriptome, and histopathological analyses showed that earthworms suffered from oxidative and inflammatory stresses. Moreover, NPs influenced the osmoregulatory metabolism of earthworms as NPs damaged intestinal epithelium (tissue level), increased aldosterone-regulated sodium reabsorption (transcriptome level), inositol phosphate metabolism (proteomic level) and 2-hexyl-5-ethyl-furan-3-sulfonic acid, and decreased betaine and myo-inositol concentrations (metabolic level). Transcriptional-metabolic and transcriptional-proteomic analyses revealed that NPs disrupted earthworm carbohydrate and arachidonic acid metabolisms. Our multi-level investigation indicates that NPs at a relatively low concentration induced toxicity to earthworms and suggests that NPs pollution has significant environmental toxicity risks for soil fauna.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Oligoquetos/metabolismo , Microplásticos/toxicidade , Poluentes do Solo/metabolismo , Poliestirenos/metabolismo , Proteômica , Betaína/metabolismo , Aldosterona/análise , Aldosterona/metabolismo , Ácido Araquidônico/metabolismo , Solo , Sódio , Ácidos Sulfônicos , Furanos , Carboidratos , Fosfatos de Inositol/metabolismo
2.
Theriogenology ; 195: 122-130, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332371

RESUMO

Taihang chickens are a domestic breed distributed throughout Hebei province in the Taihang Mountains of China and are characterized by their high meat and egg quality. However, the relatively limited egg production by this breed constrains their more widespread commercial utilization. The follicle selection process is closely linked to oocyte development and ovulation, making it a key determinant of laying performance and fecundity in hens. To understand the biological basis for such follicle selection and to identify the associated regulatory pathways, we conducted a genome-wide analysis of long noncoding RNAs (lncRNAs) and mRNAs from the pre-hierarchical follicles and hierarchical follicles of Taihang laying hens. We identified 81 lncRNAs and 528 mRNAs that were differentially expressed during follicle selection, and integrated network analyses suggested that these RNAs were associated with the cell cycle, focal adhesion, oocyte meiosis, peroxisome proliferator-activated receptor signaling, and steroid hormone biosynthesis pathways. The identified lncRNAs were also predicted to influence a series of target genes in cis and trans, suggesting that they may be important regulators of ovarian follicular development. Overall, the present analysis of lncRNA and mRNA expression patterns associated with ovarian follicle development offers a new foundation for future studies of reproductive physiology in Taihang chickens, highlighting new opportunities to improve the laying performance of this important domestic breed.


Assuntos
RNA Longo não Codificante , Animais , Feminino , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Galinhas/genética , Folículo Ovariano , Ovulação/genética
3.
Theriogenology ; 195: 217-228, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368116

RESUMO

Cattleyaks are equally adaptable to harsh environment as yaks, but produce far more milk and meat in terms of quality and quantity. However, male cattleyaks with active secondary sexuality are infertile and have restricted productivity and breeding of yaks. Much researches continue to be done in regard to the differences in transcriptome profiling in cattleyak epididymis with respect to yak epididymis. The caput segment of the epididymis is highly specialized for the initiation of spermatozoa maturation, synthesis and secretion. We used RNA-Seq technology to comparatively analyze differentially expressed genes (DEGs) associated with sperm maturation between the caput epididymis of yak and cattleyak. Transcriptomic profiling identified 109 DEGs in which 44 were upregulated and 65 were downregulated. 8 DEGs were validated by quantitative real-time PCR. DEGs were analyzed by GO and KEGG analysis to screen the key genes involved in sperm maturation. The upregulation of PAOX and ATP2C2 may be associated with toxicity and apoptosis resistance in cattleyak with respect to yak. However, downregulated DEFB109, DEFB121, DEFB123, DEFA1, LY6G5C, SLC13A2, CST3, CRYBA4 and ADAM28 were associated with innate immune response, sperm maturation, motility and antimicrobial functions. AMPK and Hedgehog signaling pathways were involved in the top-listed five significantly enriched pathways, and the downregulation of HNF4α and LRP2 may have contributed to infertility in cattleyak. The data provide a powerful resource, contributing to the knowledge on the molecular mechanisms underlying male cattleyak infertility.


Assuntos
Doenças dos Bovinos , Infertilidade Masculina , Masculino , Animais , Bovinos/genética , Proteínas Hedgehog , Transcriptoma , Epididimo , Sêmen , Perfilação da Expressão Gênica/veterinária , Infertilidade Masculina/veterinária , Doenças dos Bovinos/genética
4.
J Clin Transl Hepatol ; 11(1): 45-57, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36406315

RESUMO

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease caused by over-nutrition. Impaired autophagy is closely related to NAFLD progression. Recently, ubiquitin-specific peptidase-10 (USP10) was reported to ameliorate hepatic steatosis, but the underlying mechanism is still unclear. In view of the potential effects of USP10 on autophagy, we investigated whether USP10 alleviated steatosis through autophagy. Methods: HepG2 cells were treated with palmitic acid (PA) to model NAFLD in vitro. Lentivirus was used to regulate USP10 level in cells. Autophagic regulators were used to autophagic progression in cells. Western blotting, real-time fluorescence quantitative polymerase chain reaction, lipid drop staining and immunofluorescent staining were performed to determine the effect of USP10 on lipid autophagy. Student's t-test and Tukey's post hoc test were used to compare the means among groups. Results: PA induced cellular steatosis with dependance on autophagy. USP10 overexpression alleviated PA-induced steatosis, restored autophagic activity, promoted autophagic flux, including synthesis and degradation of autophagosomes, and lipid-targeted autophagy. In the presence of autophagy inhibitors, the protective effectiveness of USP10 on steatosis decreased. Furthermore, the specific inhibitor to C-jun N-terminal protein kinase-1 (JNK1), DB07268, abolished USP10-induced autophagy. However, during early stage inhibition of JNK1, compensatory expression of tuberous sclerosis complex-2 (TSC2) maintained autophagy. The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level. Functionally, JNK1 and TSC2 were involved in the lipid-lowering effect of USP10. Conclusions: USP10 alleviated hepatocellular steatosis in autophagy-dependent manner. JNK1/TSC2 signaling pathways were required for USP10-induced autophagy.

5.
Neural Regen Res ; 18(3): 603-608, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018184

RESUMO

ß2-Microglobulin (ß2M), a component of the major histocompatibility complex class I molecule, is associated with aging-related cognitive impairment and Alzheimer's disease. Although upregulation of ß2M is considered to be highly related to ischemic stroke, the specific role and underlying mechanistic action of ß2M are poorly understood. In this study, we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery. We found that ß2M levels in the cerebral spinal fluid, serum, and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period. RNA interference was used to inhibit ß2M expression in the acute period of cerebral stroke. Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreased ß2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits, respectively. Notably, glial cell, caspase-1 (p20), and Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation as well as production of the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α were also effectively inhibited by ß2M silencing. These findings suggest that ß2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.

6.
Cell Prolif ; : e13349, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316968

RESUMO

OBJECTIVES: Elevated thioredoxin-interacting protein (TXNIP)-induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP in DKD remain largely unclear. MATERIALS AND METHODS: Transcriptomic analysis identified a novel long noncoding RNA-Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)-which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions. We focused on revealing the functions of PWARSN in regulating TXNIP-mediated pyroptosis in PTECs by targeting PWARSN expression via lentivirus-mediated overexpression and CRISPR-Cas9-based knockout in vitro and overexpressing PWARSN in the renal cortex by AAV-9 targeted injection in vivo. A number of molecular techniques disclosed the mechanisms of PWARSN in regulating TXNIP induced-pyroptosis in DKD. RESULTS: TXNIP-NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and PTEC pyroptosis were activated in the renal tubules of patients with DKD and in diabetic mice. Then we explored that PWARSN enhanced TXNIP-driven PTECs pyroptosis in vitro and in vivo. Mechanistically, cytoplasmic PWARSN sponged miR-372-3p to promote TXNIP expression. Moreover, nuclear PWARSN interacted and facilitated RNA binding motif protein X-linked (RBMX) degradation through ubiquitination, resulting in the initiation of TXNIP transcription by reducing H3K9me3-enrichment at the TXNIP promoter. Further analysis indicated that PWARSN might be a potential biomarker for DKD. CONCLUSIONS: These findings illustrate distinct dual molecular mechanisms for PWARSN-modulated TXNIP and PTECs pyroptosis in DKD, presenting PWARSN as a promising therapeutic target for DKD.

7.
Mitochondrial DNA B Resour ; 7(10): 1876-1878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325284

RESUMO

Elaeagnus henryi Warb. ex Diels belongs to the Elaeagnaceae. Here, we reveal the complete chloroplast genome of Elaeagnus henryi. The complete chloroplast genome is 152,244 bp in length and contains a large single-copy (LSC) region of 82,235 bp, a small single-copy (SSC) region of 18,279 bp and a pair of inverted repeats (IRs) of 25,865 bp. There are 126 genes, including 81 protein-coding, 37 transfer RNA (tRNA), and eight ribosomal RNA (rRNA) genes. The total GC content of the chloroplast genome sequence is 37.1%. The maximum-likelihood phylogenetic analysis indicated that E. henryi was sister to Elaeagnus pungens (MW145133). The result may be because the species are advanced and developed from the same ancestor.

8.
Front Plant Sci ; 13: 1036369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325540

RESUMO

A change in precipitation can profoundly change the structure of soil microbial communities, especially in arid and semi-arid areas which are limited by moisture conditions. Therefore, it is crucial to explore how soil bacterial community composition and diversity will respond to variation in precipitation. Here we conducted a precipitation control experiment to simulate precipitation change by reducing and increasing rainfall by 25%, 50%, and 75% in the alpine grasslands of northern Tibet. The composition, diversity, and species interaction network of soil microbial community were studied by high-throughput sequencing, and the relationship between microbial community species and soil environmental factors was analyzed. Our results showed that Proteobacteria (45%-52%) and Actinobacteria (37%-45%) were the dominant bacteria in the soil. The alpha diversity index based on Shannon, Chao1, and Simpson indices revealed that precipitation change had no significant effect on richness and evenness of soil microbial communities. Non-metric multidimensional scaling (NMDS) and analysis of similarities (ANOSIM) showed that a clear separation of soil microbial communities between D2(-50%),D3(-75%) and W2(+50%), W3(+75%) treatments. The microbial interaction network indicated that the water-increasing treatment group had closer connections, and Proteobacteria and Actinomycetes were the core species. Furthermore, there was a stronger positive correlation between species in the water-reducing treatment group, the contribution of Proteobacteria decreased significantly, the role of connecting hub decreased, and Actinomycetes became the most important core microbial species. In addition, soil water content (SWC) and available phosphorus (AP) were closely related to the variations in soil microbial compositions. The findings of this study provide a theoretical basis for the driving mechanism of global climate change on soil microbial community and grassland ecosystem in alpine grassland.

9.
Support Care Cancer ; 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322246

RESUMO

PURPOSE: We aimed to assess the impact of aerobic exercise (AE) on parameters related to cardiotoxicity in breast cancer (BC) patients receiving anthracycline or trastuzumab. METHODS: We performed a systematic review and meta-analysis of comparative studies on AE via the screening of standard databases from their inception to January 18, 2022. The risk of bias was assessed qualitatively using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were analyzed quantitatively using fixed effects meta-analysis and subgroup analysis in RevMan software. Notable outcomes included imaging outcomes of cardiotoxicity, cardiorespiratory fitness, and cardiac biomarkers. RESULTS: A meta-analysis of the pooled evidence obtained from seven studies revealed that AE significantly increased peak oxygen consumption (VO2 peak) and E/A values, compared to the values observed during usual care. Moreover, AE was safe and feasible, and was associated with a lower risk of adverse effects, a higher participation rate, and better results, when combined with resistance exercise. CONCLUSION: In BC patients receiving anthracyclines or trastuzumab, the effects of AE on the levels of cardiotoxicity were mixed; the diastolic functions and VO2 peak values were improved, biomarkers were not affected, and the overall improvements in the levels of cardiotoxicity were promising, despite the use of different exercise parameters.

10.
Front Pharmacol ; 13: 910722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330095

RESUMO

Background: Immune checkpoint inhibitors combined chemotherapy (ICIC) are widely used for various types of lung cancer in the past decade. However, ICIC related adverse events (AEs) are more serious than immune-related adverse events (irAE) or cytotoxic chemotherapy alone. Objective: This prospective interventional study aimed to evaluate the impact of the pharmaceutical care program in reducing adverse events and analyze pharmacy interventions in patients with NSCLC who receive ICIC therapies. Method: NSCLC patients were enrolled in this study, the pharmaceutical care program was introduced after patients received the second cycle ICIC therapies, and were followed by the pharmacist for 6 months after hospital discharge. The percentages of adverse events between patients in and after the first two cycles were analyzed and compared. Results: After the first two treatment cycles, the clinical pharmacist proposed 67 interventions in 30 patients. The most frequent types of intervention were drug discontinuation (40.3%, 27/67) followed by drug modification (14.9%, 10/67). There were significant decreases in AEs after the second cycle with respect to nausea (≥grade-2, 14% vs. 28.3%, p = 0.039), constipation (≥grade-2, 8.8% vs. 21.7%, p = 0.039), diarrhea (≥grade-2, 6% vs. 16.7%, p = 0.031), and myelosuppression (≥grade-2, 15.8% vs. 30.0%, p = 0.022). Conclusion: Provision of pharmaceutical care for NSCLC patients receiving ICIC therapies can optimize drug therapy and reduce adverse events.

11.
J Bone Joint Surg Am ; 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36325763

RESUMO

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm2) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

12.
J Hazard Mater ; 443(Pt B): 130288, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36335899

RESUMO

Increasing investigations explore the effects of plastic pollutants on bacterial communities, diversity, and functioning in various ecosystems. However, the impact of microplastics (MPs) on the eukaryotic community, microbial assemblages, and interactions is still limited. Here, we investigated bacterial and micro-eukaryotic communities and functioning in soils with different concentrations of phenol formaldehyde-associated MPs (PF-MPs), and revealed the factors, such as soil properties, microbial community assembly, and interactions between microbes, influencing them. Our results showed that a high concentration (1%) of PF-MPs decreased the microbial interactions and the contribution of deterministic processes to the community assembly of microbes, and consequently changed the communities of bacteria, but not eukaryotes. A significant and negative relationship was determined between N2O emission rate and functional genes related to nitrification, indicating that the competitive interactions between functional microbes would affect the nitrogen cycling of soil ecosystem. We further found that vegetable biomass weakly decreased in treatments with a higher concentration of PF-MPs and positively related to the diversity of micro-eukaryotic communities and functional diversity of bacterial communities. These results suggest that a high concentration of the PF-MPs would influence crop growth by changing microbial communities, interactions, and eukaryotic and functional diversity. Our findings provide important evidence for agriculture management of phenol formaldehyde and suggest that we must consider their threats to microbial community compositions, diversity, and assemblage in soils due to the accumulation of PF-MPs widely used in the field.

13.
Int J Sports Med ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36377188

RESUMO

We investigated the effects of 12-week brisk walking on chronotropic response in hypertensive patients aged 40-69. 77 participants in exercise group underwent 12-week brisk walking, while 66 participants in control group received health education. Chronotropic parameters, resting blood pressure, and physical fitness including peak oxygen consumption (VO2peak) were measured. After 12 weeks, the systolic blood pressure (SBP) was decreased (-6.104 mmHg, 95%CI -8.913 to -3.295 mmHg, P<0.0001), while metabolic chronotropic relationship (MCR) slope and VO2peak were increased (0.073, 95%CI 0.001 to 0.145, P=0.046; 1.756 mL/kg/min, 95%CI 0.891 to 2.622 mL/kg/min, P<0.0001) in exercise group compared to baseline. The chronotropic response index (CRI) at 25-75W load were decreased (-0.210, 95%CI -0.307 to -0.112, P<0.0001; -0.144, 95%CI -0.204 to -0.083, P<0.0001; -0.078, 95%CI -0.135 to -0.022, P=0.007) in control group after 12 weeks. The relative changes (%Δ) of systolic and diastolic blood pressure were negatively correlated with %ΔVO2peak (r=-0.233, r=-0.187), while %ΔMCR and %ΔCRI at 50-75W load were positively correlated with %ΔVO2peak after 12 weeks (r=0.330, r=0.282, r=0.370). %ΔSBP was also positively correlated with %ΔMCR (r=-0.213). In conclusion, 12-week brisk walking reduced SBP by improving chronotropic response in hypertensive patients aged 40-69. The enhanced chronotropic response was associated with enhanced cardiorespiratory fitness.

14.
Opt Express ; 30(23): 42728-42737, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366720

RESUMO

Resonant integrated optical gyroscopes (RIOGs) can integrate discrete optical components as a promising candidate for high-performance micro-optical gyroscopes. However, the current RIOG still consists of discrete elements due to the difficulty and complexity of heterogeneous integration of resonator and modulators. This paper presents on-chip integration of optical functional components including modulator, resonator, beam splitter, and coupler for the organic-polymer-based RIOG. Simple integrated optical processes such as spin coating, lithography, and etching can realize RIOG chips with low cost, size, weight, and power (CSWaP) features. Thereinto, the electro-optic modulator (EOM) fabricated by self-synthesized electro-optic (EO) polymer (side chain bonded polyurethane imide) exhibits less than 2 V half-wave voltage, which is half of the lithium niobate (LiNbO3) modulator. With respect to the resonator, a quality factor of approximately million was achieved using low-loss fluorinated polymer. In addition, the angular velocity sensing of RIOG was also investigated. By demonstrating the monolithic integration of the resonator and modulators, such an all-polymer RIOG chip prototype builds the technical foundation for the precision fully integrated optical gyroscope.

15.
Environ Res ; : 114778, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36368374

RESUMO

A PbO2 electrode integrating electrocatalytic and adsorptive functions was successfully fabricated by embedding layer-by-layer graphene nanoplatelets (GNPs) into ß-PbO2 active layer (GNPs/PbO2) and employed as anode for high-efficient removal of sulfadiazine (SDZ). In electrochemical degradation experiments, SDZ was quickly enriched on the surface of GNPs/PbO2 film via adsorption and then oxidized by ⋅OH in-site. In terms of the electrocatalytic performance and adsorption of electrode, the optimal electrodeposition time for each ß-PbO2 outer layer was 4 min (GNPs/PbO2-4). Compared with conventional PbO2 electrode, the layer-by-layer GNPs resulted in the smaller crystal size and denser surface of PbO2 electrode, thus facilitating the generation of active oxygen species. At the same time, the specific surface area, oxygen evolution potential (OEP) of the anode were enhanced and the charge-transfer resistance was reduced. For GNPs/PbO2-4 anode, the optimal conditions of electrochemical oxidation of SDZ were identified as initial pH 9, 50 mg/L of SDZ and 20 mA/cm2 of current density using response surface methodology (RSM), 98.15% of SDZ could be removed in this case. The contribution of radical oxidation and non-radical oxidation to SDZ removal was about 79% and 21%, respectively. Moreover, the reaction pathways of SDZ on the GNPs/PbO2-4 electrode involving hydroxylation, radical reaction and ring cleavage were speculated. Finally, the continuous SDZ degradation and accelerated service lifetime test suggested the GNPs/PbO2-4 electrode was shown to be stable and repeatable, and the Pb2+ concentration was measured to ensure the safety of the treated solution. Consequently, the above findings provide an innovative way to design and prepare an effective and stable PbO2 electrode for electrochemical degradation of antibiotic wastewater.

16.
Am J Cancer Res ; 12(10): 4502-4519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36381328

RESUMO

Tumor metastasis is the major cause of cancer mortality; therefore, it is imperative to discover effective therapeutic drugs for anti-metastasis therapy. In the current study, we investigated whether ivermectin (IVM), an FDA-approved antiparasitic drug, could prevent cancer metastasis. Colorectal and breast cancer cell lines and a cancer cell-derived xenograft tumor metastasis model were used to investigate the anti-metastasis effect of IVM. Our results showed that IVM significantly inhibited the motility of cancer cells in vitro and tumor metastasis in vivo. Mechanistically, IVM suppressed the expressions of the migration-related proteins via inhibiting the activation of Wnt/ß-catenin/integrin ß1/FAK and the downstream signaling cascades. Our findings indicated that IVM was capable of suppressing tumor metastasis, which provided the rationale on exploring the potential clinical application of IVM in the prevention and treatment of cancer metastasis.

17.
Exp Dermatol ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394347

RESUMO

BACKGROUND: Mutations in the γ-secretase complex have been well described in familial hidradenitis suppurativa (HS). No gene mutations have been identified in sporadic HS, which comprises 60-70% of all HS cases. Obesity and smoking are risk factors for HS and are closely related to DNA methylation, an essential epigenetic phenomenon. Hence, we hypothesized that epigenetic modifications might be involved in sporadic HS. OBJECTIVES: To investigate genes with aberrant methylation in sporadic HS cases and assess their expression in skin lesions and blood from patients with HS. METHODS: Skin lesion samples and corresponding normal skin were obtained from three patients with HS and subjected to whole-genome DNA methylation sequencing. Blood samples were collected from 20 patients with HS and 20 healthy controls (HCs). The HS mouse model was established by applying tamoxifen to NcstnΔKC mice. Target gene expression was analyzed by immunohistochemistry, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA), and semiquantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: Among 10,807 differentially methylated genes, we filtered 2,101 genes with hypermethylated promoter regions, and following bioinformatics analyses, we focused on CXC chemokine ligand 16 (CXCL16). Subsequent functional experiments confirmed the downregulation of CXCL16 and its receptor, CXC chemokine receptor (CXCR) 6, in skin tissue from HS patients and NcstnΔKC mice. Serum CXCL16 concentrations were also significantly decreased in patients with HS. CONCLUSIONS: Our data revealed the downregulation of CXCL16 and CXCR6 in HS.

18.
Molecules ; 27(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364248

RESUMO

Accumulating evidence has shown that Parkinson's disease (PD) is a systemic disease other than a mere central nervous system (CNS) disorder. One of the most important peripheral symptoms is gastrointestinal dysfunction. The enteric nervous system (ENS) is regarded as an essential gateway to the environment. The discovery of the prion-like behavior of α-synuclein makes it possible for the neurodegenerative process to start in the ENS and spread via the gut-brain axis to the CNS. We first confirmed that synucleinopathies existed in the stomachs of chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid (MPTP/p)-induced PD mice, as indicated by the significant increase in abnormal aggregated and nitrated α-synuclein in the TH-positive neurons and enteric glial cells (EGCs) of the gastric myenteric plexus. Next, we attempted to clarify the mechanisms in single MPTP-injected mice. The stomach naturally possesses high monoamine oxidase-B (MAO-B) activity and low superoxide dismutase (SOD) activity, making the stomach susceptible to MPTP-induced oxidative stress, as indicated by the significant increase in reactive oxygen species (ROS) in the stomach and elevated 4-hydroxynonenal (4-HNE) in the EGCs after MPTP exposure for 3 h. Additionally, stomach synucleinopathies appear before those of the nigrostriatal system, as determined by Western blotting 12 h after MPTP injection. Notably, nitrated α-synuclein was considerably increased in the EGCs after 3 h and 12 h of MPTP exposure. Taken together, our work demonstrated that the EGCs could be new contributors to synucleinopathies in the stomach. The early-initiated synucleinopathies might further influence neighboring neurons in the myenteric plexus and the CNS. Our results offer a new experimental clue for interpreting the etiology of PD.


Assuntos
Intoxicação por MPTP , Doença de Parkinson , Transtornos Parkinsonianos , Sinucleinopatias , Camundongos , Animais , alfa-Sinucleína , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Neuroglia , Estômago
19.
Plant Physiol Biochem ; 193: 110-123, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36347113

RESUMO

The most hazardous abiotic stress, salinity, restricted the world crop production, and grain chalkiness affected the grain quality to limit consumers' acceptance. The basic helix-loop-helix (bHLH) proteins modulate massive biological processes in plants. Here the CRISPR/Cas9 gene editing mutants were obtained to detect the function of OsbHLH044. The loss-of-function of OsbHLH044 mutants showed numerous altered plant phenotypes. Notably, the osbhlh044 mutants resulted in prominently reduced morphological and physiological parameters under salt stress. Lower antioxidant activities and higher lipid peroxidation and hydrogen peroxide (H2O2) accumulation in the osbhlh044 mutants caused salinity sensitivity due to elevated reactive oxygen species (ROS). Under salt stress, both shoots and roots of the osbhlh044 mutants acquired higher Na+. Moreover, the expression of ion homeostasis-related genes (OsHKTs, OsHAK, OsSOSs, and OsNHX) and ABA-responsive gene (OsLEA3) was significantly altered in the osbhlh044 mutants after salt stress. The expression levels of genes coding for starch (OsAGPL1, OsSSIIa, OsWx, and OsFLO2) and seed storage proteins (GluA1 and Globulin 1) were significantly decreased, indicating that they synthesize less store starch and proteins, resulting in grain chalkiness in the osbhlh044 mutants. Yeast one Hybrid (Y1H) showed that OsbHLH044 could activate salt- (OsHKT1;3, OsHAK7, OsSOS1, OsSOS2, OsNHX2, and OsLEA3 but not OsHKT2;1), and starch-related genes (OsSSIIa, OsWx, and OsFLO2) by binding to the G-boxes of their promoters. Therefore, the OsbHLH044 gene editing mutants revealed multiple functions, specifically a positive regulator of salt stress and grain quality, which might bring new insights into the breeding of rice varieties.


Assuntos
Oryza , Oryza/metabolismo , Salinidade , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Estresse Fisiológico/genética , Amido/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Mutação/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(9): 909-914, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36377442

RESUMO

OBJECTIVE: To explore the application rules and effects of "Four Elements, One Peptide, and Two Transplantations" in the bundle treatment of the patients with coronavirus disease 2019 (COVID-19), so as to provide a scientific evidence for effective treatment and prevention of severe type. METHODS: A retrospective comparative study method was used to analyze the clinical data of COVID-19 patients admitted to Wuxi Fifth People's Hospital from January 2020 to March 2022, including demographic information, underlying diseases, clinical classification, length of hospital stay, treatment cost, clinical symptoms, laboratory tests and other key indicators, and evaluate the application rules and effect of "Four Elements, One Peptide, and Two Transplantations" in the bundle treatment of the patients with COVID-19. RESULTS: The L-type new coronavirus strain was predominant in 2020, the Delta variant in 2021, and the Omicron variant in 2022. The proportion of mild cases was highest in 2022, with the highest proportion of > 65 years old patients developing severe and critical. Among the 150 patients, the proportion of interferon use (100.0%) was the highest in the bundle treatment regimen of "Four Elements, One Peptide, and Two Transplantation". The combined use of vitamin C, interferon and thymopeptide was highest in 2022. More than 75.0% of the age > 65 years old group had underlying diseases, which was also the age group with the highest proportion of "Four Elements, One Peptide, and Two transplantations". Compared with mild cases, the age, length of hospital stay, and hospitalization cost of patients with COVID-19 increased significantly with severity. Mild, ordinary, severe, and critically ill patients all had low lymphocyte counts, with 40.0% of severe patients having the lowest lymphocyte counts within 3 days of admission. The lymphocyte count of critically ill patients was reduced or continuously reduced after admission, and the use of the "Four Elements, One Peptide, and Two transplantations" method to regulate immunity can effectively save the lives of critically ill patients. Of all cases of COVID-19 infection, 51.3% were asymptomatic, followed by respiratory symptoms (48.7%) and lung lesions (38.0%). Patients with renal dysfunction received this bundle therapy was highest, followed abnormal coagulation and abnormal liver function. This bundle therapy promoted a significant increase in CD4+ T lymphocytes and B lymphocytes in various cases. After treatment, as the virus turns negative, the proportion of M1 type macrophages increased, and the proportion of regulatory T cell (Treg cells) that suppress immunity and the infection related C-C chemokine receptor type (CCR10+) Treg cells decreased. Mild adult cases showed a great change and declined rapidly. CONCLUSIONS: Advanced age with underlying diseases is a risk factor for severe disease of COVID-19, the "Four Elements, One Peptide, and Two transplantations" bundle fine treatment of COVID-19 can improve the proportion of lymphocyte composition and organ function, which can control the occurrence and development of severe diseases. In addition to the proportion of CD4+ T cells, the changes of the M1 macrophage, total Treg cell, and CCR10+ Treg cell proportions can be used to determine disease changes of adult patients.


Assuntos
COVID-19 , Humanos , Adulto , Idoso , SARS-CoV-2 , Estado Terminal , Estudos Retrospectivos , Antivirais , Peptídeos , Interferons
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