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1.
Ecotoxicol Environ Saf ; 238: 113569, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35512470

RESUMO

Sertoli cells play a pivotal role in the complex spermatogenesis process. This study aimed to investigate the effects of PM2.5 on Sertoli cells using the TM4 cell line and a real time whole-body PM2.5 exposure mouse model, and further explore the underlying mechanisms through the application of metabolomics and transcriptomics. The results in vivo and in vitro showed that PM2.5 reduced Sertoli cells number in seminiferous tubules and inhibited cell proliferation. PM2.5 exposure also induced Sertoli cell dysfunction by increasing androgen binding protein (ABP) concentration, reducing the blood-testis barrier (BTB)-related protein expression, and decreasing glycolysis capacity and lactate production. The results of transcriptomics, metabolomics, and integrative analysis of multi-omics in the TM4 Sertoli cells revealed the activation of xenobiotic metabolism, and the disturbance of glutathione and purine metabolism after PM2.5 exposure. Further tests verified the reduced GSH/GSSG ratio and the elevation of xanthine oxidase (XO) activity in the PM2.5-exposed TM4 cells, indicating that excessive reactive oxygen species (ROS) was generated via metabolic disorder caused by PM2.5. Moreover, the redox imbalance was proved by the increase in the mitochondrial ROS level, superoxide dismutase (SOD) and catalase (CAT) activity, as well as the activation of the Nrf2 antioxidative pathway. Further study found that the redox imbalance caused by PM2.5 induced DNA damage response and cell cycle arrest. Additionally, PM2.5 induced ferroptosis through iron overload and lipid peroxidation. Taken all together, our study provided new insights for understanding proliferation inhibition and dysfunction of TM4 Sertoli cells exposed to PM2.5 via metabolic disorder and redox imbalance-mediated DNA damage response and ferroptosis.

2.
J Dent ; : 104159, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35550398

RESUMO

OBJECTIVES: To evaluate the interactions of two phosphate ester monomers [10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) and dipentaerythritol penta-acrylate phosphate (PENTA)] with hydroxyapatite and collagen and understand their influence on dentine bonding. METHODS: Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, nuclear magnetic resonance, ultraviolet-visible, and molecular docking were applied for separately evaluating the interactions of two monomers with hydroxyapatite and collagen. Hydrophilicity tests and morphological observation were employed to characterize pretreated dentine. Microtensile bond strength (µTBS) and nanoleakage were investigated to evaluate the bonding performance. Hydroxyproline assay, in situ zymography, and matrix metalloproteinase-9 (MMP-9) activity assay were used to confirm the MMP inhibition. RESULTS: Chemoanalytic characterization confirmed the interactions of 10-MDP and PENTA with hydroxyapatite and collagen. The interactions of PENTA were weaker than 10-MDP. PENTA possessed better dentine tubule sealing after etching than 10-MDP. Dentine treated with PENTA was more hydrophilic than 10-MDP. 10-MDP and PENTA treating significantly increased the initial µTBS than the control group without primer conditioning. µTBS decreased significantly during aging, and the decrease was more severe in the PENTA group than 10-MDP. The 10-MDP and PENTA groups exhibited relatively less fluorescence than the control. The relative inhibition percentages of MMP-9 decreased in the order of 10-MDP-Ca salt, 10-MDP and PENTA. The 10-MDP, PENTA, and 10-MDP-Ca salt groups showed significantly lower hydroxyproline contents than the control. CONCLUSIONS: Although PENTA adsorbed on hydroxyapatite, it did not form a stable calcium salt. The interactions of 10-MDP with hydroxyapatite and collagen are different than those of PENTA. CLINICAL SIGNIFICANCE: The sealing of dentinal tubules by PENTA and the inhibition of MMP by 10-MDP and its calcium salts contribute to improving the dentine bonding durability.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35550876

RESUMO

The unicellular green alga Chlamydomonas reinhardtii (hereafter Chlamydomonas) possesses both plant and animal attributes, and it is an ideal model organism for studies of fundamental processes such as photosynthesis, sexual reproduction, and the life cycle. N6-methyladenosine (m6A) is the most prevalent mRNA modification, and it plays important roles during sexual reproduction in animals and plants. However, the pattern and function of m6A modification during the sexual reproduction of Chlamydomonas remain unknown. Here, we performed transcriptome and methylated RNA immunoprecipitation sequencing (MeRIP) sequencing on six samples from different stages during sexual reproduction of the Chlamydomonas life cycle. The results showed that m6A modification frequently occurs at the main motif of DRAC (D = G/A/U, R = A/G) in Chlamydomonas mRNAs. Moreover, m6A peaks in Chlamydomonas mRNAs are mainly enriched in the 3' untranslated regions (3' UTR) and negatively correlated with the abundance of transcripts at each stage. In particular, there is a significant negative correlation between expression levels and m6A levels of genes in the microtubule-associated pathway, indicating that m6A modification influences the sexual reproduction and life cycle of Chlamydomonas by regulating microtubule-based movement. In summary, our findings are the first to demonstrate the distributions and the functions of m6A modification in Chlamydomonas mRNAs and provide new evolutionary insights into m6A modification in the process of sexual reproduction in other plant organisms.

4.
Anim Sci J ; 93(1): e13725, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35508764

RESUMO

In the process of modern breeding, high-concentrate diets are widely used to meet the high energy nutritional requirements of animals but change the form of access to energy and nutrients and the way the organism metabolizes them. Goat psoas major (PM) muscle is a hybrid skeletal muscle whose characteristics are important for the motility and meat quality of goats. However, there are few studies on the effects of high-concentrate diets on the muscle type and metabolic characteristics of PM in goats. In this study, two treatment groups were set up: high concentrate group (HC) and control group (C). The expression of genes related to muscle type and metabolism of the PM was examined by quantitative PCR. The results showed that high concentrate promoted the conversion of PM fibers from intermediate to slow type at the mRNA level, improved the absorption, transport, and oxidation of fat by PM, and upregulated the expression of calpain system. These changes may be regulated by the involvement of differential expression of MSTN, Myf-5, and IGF-2. These results suggest that high concentrate may exert a positive effect on skeletal muscle function, metabolism, and meat quality in goats by affecting the expression of muscle type and metabolism-related genes.


Assuntos
Dieta , Cabras , Animais , Dieta/veterinária , Cabras/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Acta Pharm Sin B ; 12(3): 1163-1185, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35530162

RESUMO

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.

6.
FASEB J ; 36(6): e22342, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35524750

RESUMO

Renal fibrosis is the final common outcome of chronic kidney disease (CKD), which remains a huge challenge due to a lack of targeted treatment. Growing evidence suggests that during the process of CKD, the integrity and function of mitochondria in renal tubular epithelial cells (TECs) are generally impaired and strongly connected with the progression of renal fibrosis. Mitophagy, a selective form of autophagy, could remove aberrant mitochondria to maintain mitochondrial homeostasis. Deficiency of mitophagy has been reported to aggravate renal fibrosis. However, whether induction of mitophagy could alleviate renal fibrosis has not been stated. In this study, we explored the effect of mitophagy activation by UMI-77, a compound recently verified to induce mitophagy, on murine CKD model of unilateral ureteral obstruction (UUO) in vivo and TECs in vitro. In UUO mice, we found the changes of mitochondrial damage, ROS production, transforming growth factor (TGF)-ß1/Smad pathway activation, as well as epithelial-mesenchymal transition phenotype and renal fibrosis, and these changes were ameliorated by mitophagy enhancement using UMI-77. Moreover, TEC apoptosis, nuclear factor (NF)-κB signaling activation, and interstitial inflammation after UUO were significantly mitigated by augmented mitophagy. Then, we found UMI-77 could effectively and safely induce mitophagy in TECs in vitro, and reduced TGF-ß1/Smad signaling and downstream profibrotic responses in TGF-ß1-treated TECs. These changes were restored by a mitophagy inhibitor. In conclusion, we demonstrated that mitophagy activation protected against renal fibrosis through improving mitochondrial fitness, downregulating TGF-ß1/Smad signaling and alleviating TEC injuries and inflammatory infiltration in kidneys.


Assuntos
Insuficiência Renal Crônica , Animais , Células Epiteliais/metabolismo , Fibrose , Rim/metabolismo , Camundongos , Mitocôndrias/metabolismo , Mitofagia , NF-kappa B/metabolismo , Insuficiência Renal Crônica/metabolismo , Sulfonamidas , Tioglicolatos , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/metabolismo
7.
Phytochemistry ; 200: 113186, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35500784

RESUMO

Eleven undescribed limonoids, cipacinerasins A-K, involving of four diverse carbon skeletal types, along with fifteen known analogues, were isolated from the branches and leaves of Cipadessa baccifera. Within them, cipacinerasins A and B feature a rearranged tetrahydropyranyl ring B formed between C-8 and C-30, are unusual miscellaneous-type limonoids. Cipacinerasins E and F are rare trijugin-type limonoids, of which the D-ring δ-lactone is cleaved. Their structures were elucidated on the basis of extensive spectroscopic data (HRESIMS, NMR, UV and IR), electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. All compounds were evaluated in vitro cytotoxicity against five human tumor cell lines (K562, HeLa, PC3, LN-Cap and Hell), and cipacinerasin E showed moderate antitumor activity with IC50 values ranging from 8.0 to 24.8 µM.

8.
Fitoterapia ; 160: 105217, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35561838

RESUMO

Two pairs of new enantiomeric flavonolignans, ±stachyols A and B (±1 and ± 2), along with two novel isoflavanelignans, stachyols C and D (3 and 4) were isolated from the roots of Indigofera stachyodes. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism (ECD) spectra, as well as quantum chemical calculations. Of those compounds, 1 and 2 represented the first examples of flavonolignans with 5-deoxyflavonoids adduct phenylpropanoids. Moreover, 3 and 4 possess an unprecedented skeleton with isoflavanes adduct phenylpropanoids. The antioxidant activity was evaluated for all compounds in terms of ABTS+ and DPPH bioassays. Compounds 3 and 4 exhibited significant radical-scavenging activity in the ABTS+ assay, with IC50 values of 15.15 and 5.83 µM, respectively.

9.
RSC Adv ; 12(6): 3243-3252, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35425400

RESUMO

Wound infection is a common clinical problem. Traditional detection methods can not provide infection early warning information in time. With the development of flexible electronics, flexible wearable devices have been widely used in the field of intelligent monitoring. Here, we describe the development of a soft wound infection monitoring system with pH sensors and temperature sensors. The measurement range of pH was 4-10, the fitting accuracy was 99.8%, and the response time was less than 6 s. The temperature sensor array showed good accuracy and short response times in the range of 30 °C to 40 °C. A series of in vitro tests and the use of a rat model of Staphylococcus aureus infection confirmed that this flexible detection system can monitor the pH and temperature changes occurring in the early stage of infection, which provides an effective reference for clinical application.

10.
Adv Healthc Mater ; : e2200287, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35488775

RESUMO

The construction of hierarchical porous structure in biomaterials is of great significance for improving nutrient transport and biological performance. However, it is still challenging to design porous bone substitutes with high strength and biological properties, which limits their clinical applications in load-bearing bone regeneration. Herein, based on hierarchical porous structure of renewable bamboo, the mineralized calcium phosphate/bamboo composite scaffolds with high strength and excellent transport performance are successfully prepared in combination of biotemplated approach and biomimetic mineralization. The mineralized biomaterials have simultaneously achieved high mechanical strength and low modulus, similar to those of cortical bone. Furthermore, the mineralized biomaterials exhibit good liquid transport capacity and can transport cells along anti-gravity direction. Based on density functional theory (DFT) calculations, the mineralized calcium phosphate reveals the optimal H2 O adsorption energy (-0.651 eV) and low diffusion energy barrier (0.743 eV), which is conducive to enhance hydrophilicity and liquid transport performance. Moreover, owing to the synergistic effect of the porous structure of biotemplate and bioactive mineralized components, the mineralized biomaterials possess enhanced bone integration and osteoconduction properties. The present study shed light on deeper understanding of mineralized biosourced materials, offering a strategy of combining green chemistry with tissue engineering to prepare eco-friendly biomaterials.

11.
Foods ; 11(7)2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35407128

RESUMO

This work studied the interactions between trehalose/chitooligosaccharide (COS) and myofibrillar protein (MP), and the effect of such interactions on the quality of meat after freezing was also evaluated. Fourier transform infrared spectroscopy showed that both trehalose and COS could enhance the content of hydrogen bonds of MP. Zeta potential measurement displayed trehalose/COS reduced the absolute value of the surface potential of MP. The results of Raman spectroscopy suggested that the hydrophobic residues of MP were more exposed after treatment with trehalose/COS. Thus, trehalose and COS could both interact with MP through non-covalent bonds. Subsequently, the evaluation of the effect of trehalose and COS on the physicochemical properties of frozen meat was conducted. Results showed that both trehalose and COS significantly reduced thawing loss of frozen meat, and sensory evaluation showed that trehalose had a better performance from the perspective of smell, texture, and overall consumer acceptance. In conclusion, trehalose/COS interacting with MP can reduce meat thawing loss, which might provide technical guidance in the quality control of frozen meat.

12.
Int J Nanomedicine ; 17: 1695-1709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444417

RESUMO

Purpose: This study aimed to investigate the hydrolytic stability of 10-methacryloyloxydecyl dihydrogen phosphate calcium (MDP-Ca) salts with nanolayered and amorphous structures in different pH environments. Methods: The MDP-Ca salts were synthesized from MDP and calcium chloride and characterized by X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to quantify the release of calcium from the synthesized MDP-Ca salt, MDP-treated hydroxyapatite (MDP-HAp), and untreated HAp after soaking in acidic and neutral solutions for 1, 7, and 30 days. To study the hydrolytic process, we carried out molecular dynamics (MD) simulations of the nanolayered MCS-MD (monocalcium salt of the MDP dimer) and DCS-MD (dicalcium salt of the MDP dimer) structures, as well as of the amorphous-phase MCS-MM (monocalcium salt of the MDP monomer). Results: The TEM images showed that the nanolayered structures were partially degraded by acid attack. Based on the ICP-MS results, the hydrolysis rate of the MDP-Ca salt in acidic and neutral environments followed the order HAp > MDP-HAp > MDP-Ca salt. The MD simulations showed that, in acidic environments, clusters of MDP remained aggregated and all Ca2+ ions separated from the MDP monomer to interact with water molecules in aqueous solution. In neutral environments, Ca2+ ions always interacted with phosphate groups, OH- ions, and water molecules to form clusters centered on Ca2+ ions. Conclusion: MDP-Ca presented higher hydrolysis rates in acidic than neutral environments. Nanolayered MCS-MD possessed the highest resistance to acidic hydrolysis, followed by amorphous MCS-MM and DCS-MD.


Assuntos
Colagem Dentária , Sais , Cálcio/análise , Dentina/química , Hidrólise , Teste de Materiais , Metacrilatos/química , Cimentos de Resina/química , Sais/análise , Água
13.
Front Immunol ; 13: 805420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359928

RESUMO

The interstitium of kidney involves a variety of components including resident immune cells, in particular mononuclear phagocytes. However, many proposed markers for distinguishing macrophages or dendritic cells are, in fact, shared by the majority of renal mononuclear phagocytes, which impedes the research of kidney diseases. Here, by employing a flow cytometry strategy and techniques of fate mapping, imaging and lineage depletion, we were able to demarcate renal monocytes, macrophages and dendritic cells and their subsets in mice. In particular, using this strategy, we found that even in steady state, the renal macrophage pool was continuously replenished by bone marrow-derived monocytes in a stepwise process, i.e., from infiltration of classical monocyte, to development of nonclassical monocyte and eventually to differentiation to macrophages. In mechanism, we demonstrated that the ligation of tissue-anchored CX3CL1 and monocytic CX3CR1 was required for promoting monocyte differentiation to macrophages in the kidney, but CX3CL1-CX3CR1 signaling was dispensable in monocyte infiltrating into the kidney. In addition to the bone marrow-derived macrophages, fate mapping in adult mice revealed another population of renal resident macrophages which were embryo-derived and self-maintaining. Thus, the dissecting strategies developed by us would assist in exploration of the biology of renal mononuclear phagocytes.


Assuntos
Macrófagos , Monócitos , Animais , Citometria de Fluxo , Rim , Contagem de Leucócitos , Camundongos
14.
Adv Mater ; : e2202063, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443084

RESUMO

Proton conduction underlies many important electrochemical technologies. A family of new proton electrolytes is reported: acid-in-clay electrolyte (AiCE) prepared by integrating fast proton carriers in a natural phyllosilicate clay network, which can be made into thin-film (tens of micrometers) fluid-impervious membranes. The chosen example systems (sepiolite-phosphoric acid) rank top among the solid proton conductors in terms of proton conductivities (15 mS cm-1 at 25 °C, 0.023 mS cm-1 at -82 °C), electrochemical stability window (3.35 V), and reduced chemical reactivity. A proton battery is assembled using AiCE as the solid electrolyte membrane. Benefitting from the wider electrochemical stability window, reduced corrosivity, and excellent ionic selectivity of AiCE, the two main problems (gassing and cyclability) of proton batteries are successfully solved. This work draws attention to the element cross-over problem in proton batteries and the generic "acid-in-clay" solid electrolyte approach with superfast proton transport, outstanding selectivity, and improved stability for room- to cryogenic-temperature protonic applications.

15.
Adv Sci (Weinh) ; : e2200670, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35478383

RESUMO

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/ß-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.

16.
J Clin Invest ; 132(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229723

RESUMO

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/metabolismo , Antígeno CD47/genética , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Transdução de Sinais
17.
Endocrine ; 76(2): 294-303, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35246764

RESUMO

PURPOSE: We aimed to illustrate gut microbiota and short chain fatty acid (SCFA) levels in diabetic nephropathy (DN) patients, and investigate the mechanism of sodium butyrate in diabetic mellitus (DM) rats. METHODS: Gut microbiota and serum SCFA levels were measured by 16S rDNA and GC-MS. After being built by streptozotocin (DM rats), the DM rats were administered 300 mg/kg sodium butyrate for 12 weeks (DM + BU rats). Gut microbiota, serum and fecal butyrate level were measured. RT-PCR, WB and transmission electron microscopy were performed to explore LC3mRNA or LC3B protein expression, and autophagosomes in kidney tissues. AMPK/mTOR protein expression in renal tissue were also measured. RESULTS: The gut microbial dysbiosis was found in DM and DN groups, and some SCFAs-producing bacteria were decreased in DN group. The serum butyrate concentrations were lower in SCFA-DN group compared with SCFA-HC group and SCFA-DM group in the other cohort. Serum butyrate level was positively correlated with eGFR. Sodium butyrate increased serum and fecal butyrate levels, and improved the enlargement of glomerular area and fibronectin and collagen IV expressions in renal tissues in DM + BU rats. The LC3 mRNA, LC3BII/I ratio and number of autophagosomes were increased in renal tissue of DM + BU rats. Higher p-AMPK/AMPK ratio and lower p-mTOR/ mTOR ratio were shown in renal tissue of DM + BU rats compared with DM rats. CONCLUSIONS: We found the decrease in SCFAs-producing bacteria and low SCFAs concentrations in DN patients. Oral butyrate supplementation may improve kidney injury in DM rats, possibly by increasing autophagy via activating AMPK/mTOR pathway.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Microbioma Gastrointestinal , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Ácido Butírico/metabolismo , Ácido Butírico/farmacologia , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/metabolismo , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Feminino , Humanos , Rim/metabolismo , Masculino , Ratos , Serina-Treonina Quinases TOR/metabolismo
18.
Oncogene ; 41(18): 2651-2662, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35351997

RESUMO

The role of glucose-6-phosphate dehydrogenase (G6PD) in human cancer is incompletely understood. In a metabolite screening, we observed that inhibition of H3K9 methylation suppressed aerobic glycolysis and enhances the PPP in human mesothelioma cells. Genome-wide screening identified G6PD as an H3K9me3 target gene whose expression is correlated with increased tumor cell apoptosis. Inhibition of aerobic glycolysis enzyme LDHA and G6PD had no significant effects on tumor cell survival. Ablation of G6PD had no significant effect on human mesothelioma and colon carcinoma xenograft growth in athymic mice. However, activation of G6PD with the G6PD-selective activator AG1 induced tumor cell death. AG1 increased tumor cell ROS production and the resultant extrinsic and intrinsic death pathways, mitochondrial processes, and unfolded protein response in tumor cells. Consistent with increased tumor cell death in vitro, AG1 suppressed human mesothelioma xenograft growth in a dose-dependent manner in vivo. Furthermore, AG1 treatment significantly increased tumor-bearing mouse survival in an intra-peritoneum xenograft athymic mouse model. Therefore, in human mesothelioma and colon carcinoma, G6PD is not essential for tumor growth. G6PD acts as a metabolic checkpoint to control metabolic flux towards the PPP to promote tumor cell apoptosis, and its expression is repressed by its promotor H3K9me3 deposition.


Assuntos
Carcinoma , Mesotelioma , Animais , Modelos Animais de Doenças , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , Mesotelioma/genética , Camundongos , Camundongos Nus , Via de Pentose Fosfato , Espécies Reativas de Oxigênio/metabolismo
19.
J Ethnopharmacol ; 292: 115194, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35304276

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is recognized as one of the most prevalent neurodegenerative diseases. Lingguizhugan decoction (LGZGD) is a classical traditional Chinese medicine (TCM). Many studies have shown that LGZGD can alleviate the symptoms of AD. AIM OF THE STUDY: The aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on Aß25-35-induced PC12 cells. MATERIALS AND METHODS: PC12 cells were used MTT assays, ELISA, fluorescence probe analyses, Hoechst 33342 staining, immunofluorescent staining and western blot analyses were systematically conducted to evaluate the underlying mechanisms of LGZGD. RESULTS: In Aß25-35-induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNF-α, IL-1ß, IL-6, MDA and ROS, increased the activity of GSH-Px, inhibited cell apoptosis, downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. Moreover, LGZGD modulated the NF-κB/MAPK signaling pathways by upregulating the levels of IκBα and phospho-ERK, while downregulating the levels of phospho-p65, phospho-IκBα, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-κB p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3ß and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. CONCLUSIONS: Taken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by Aß25-35 by modulating the NF-κB/MAPK signaling pathways in PC12 cells.


Assuntos
Doença de Alzheimer , NF-kappa B , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Apoptose , Glicogênio Sintase Quinase 3 beta/metabolismo , Sistema de Sinalização das MAP Quinases , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Células PC12 , Ratos
20.
Adv Mater ; : e2109055, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258117

RESUMO

Advances in wearable epidermal sensors have revolutionized the way that physiological signals are captured and measured for health monitoring. One major challenge is to convert physiological signals to easily readable signals in a convenient way. One possibility for wearable epidermal sensors is based on visible readouts. There are a range of materials whose optical properties can be tuned by parameters such as temperature, pH, light, and electric fields. Herein, this review covers and highlights a set of materials with tunable optical properties and their integration into wearable epidermal sensors for health monitoring. Specifically, the recent progress, fabrication, and applications of these materials for wearable epidermal sensors are summarized and discussed. Finally, the challenges and perspectives for the next generation wearable devices are proposed.

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