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1.
J Cell Physiol ; 239(4): e31184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38197464

RESUMO

Interleukin-38 (IL-38), recently recognized as a cytokine with anti-inflammatory properties that mitigate type 2 diabetes, has been associated with indicators of insulin resistance and nonalcoholic fatty liver disease (NAFLD). This study investigated the impact of IL-38 on hepatic lipid metabolism and endoplasmic reticulum (ER) stress. We assessed protein expression levels using Western blot analysis, while monodansylcadaverine staining was employed to detect autophagosomes in hepatocytes. Oil red O staining was utilized to examine lipid deposition. The study revealed elevated serum IL-38 levels in high-fat diet (HFD)-fed mice and IL-38 secretion from mouse keratinocytes. IL-38 treatment attenuated lipogenic lipid accumulation and ER stress markers in hepatocytes exposed to palmitate. Furthermore, IL-38 treatment increased AMP-activated protein kinase (AMPK) phosphorylation and autophagy. The effects of IL-38 on lipogenic lipid deposition and ER stress were nullified in cultured hepatocytes by suppressing AMPK through small interfering (si) RNA or 3-methyladenine (3MA). In animal studies, IL-38 administration mitigated hepatic steatosis by suppressing the expression of lipogenic proteins and ER stress markers while reversing AMPK phosphorylation and autophagy markers in the livers of HFD-fed mice. Additionally, AMPK siRNA, but not 3MA, mitigated IL-38-enhanced fatty acid oxidation in hepatocytes. In summary, IL-38 alleviates hepatic steatosis through AMPK/autophagy signaling-dependent attenuation of ER stress and enhancement of fatty acid oxidation via the AMPK pathway, suggesting a therapeutic strategy for treating NAFLD.


Assuntos
Estresse do Retículo Endoplasmático , Interleucina-8 , Hepatopatia Gordurosa não Alcoólica , Obesidade , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Palmitatos/farmacologia , RNA Interferente Pequeno/metabolismo , Interleucina-8/farmacologia , Interleucina-8/uso terapêutico
2.
Biochem Biophys Res Commun ; 703: 149671, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38367515

RESUMO

Interleukin-27 (IL-27) is a recently discovered cytokine that has been implicated in inflammatory and metabolic conditions, such as atherosclerosis and insulin resistance. However, the mechanisms by which IL-27 attenuates hepatic lipid accumulation in hyperlipidemic conditions and counteracts endoplasmic reticulum (ER) stress, a known risk factor for impaired hepatic lipid metabolism, have not been elucidated. This in vitro study was designed to examine the effect of IL-27 on hepatic lipid metabolism. The study included the evaluation of lipogenesis-associated proteins and ER stress markers by Western blotting, the determination of hepatic lipid accumulation by Oil Red O staining, and the examination of autophagosome formation by MDC staining. The results showed that IL-27 treatment reduced lipogenic lipid deposition and the expression of ER stress markers in cultured hepatocytes exposed to palmitate. Moreover, treatment with IL-27 suppressed CD36 expression and enhanced fatty acid oxidation in palmitate-treated hepatocytes. The effects of IL-27 on hyperlipidemic hepatocytes were attenuated when adenosine monophosphate-activated protein kinase (AMPK) or 3-methyladenine (3 MA) were inhibited by small interfering RNA (siRNA). These results suggest that IL-27 attenuates hepatic ER stress and fatty acid uptake and stimulates fatty acid oxidation via AMPK/autophagy signaling, thereby alleviating hepatic steatosis. In conclusion, this study identified IL-27 as a promising therapeutic target for nonalcoholic fatty liver disease (NAFLD).


Assuntos
Interleucina-27 , Hepatopatia Gordurosa não Alcoólica , Humanos , Interleucina-27/metabolismo , Interleucina-27/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Hepatócitos/metabolismo , Estresse do Retículo Endoplasmático , Ácidos Graxos/metabolismo , Palmitatos/farmacologia , Palmitatos/metabolismo
3.
Biochem Biophys Res Commun ; 694: 149407, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38154209

RESUMO

Interleukin-38 (IL-38), a member of the IL-1 family, is known for its anti-inflammatory properties mediated through ligand signaling in various disease models. It plays a significant role in atherosclerosis development, forming a theoretical basis for therapeutic strategies. However, the direct effects of IL-38 on atherogenic responses in the vascular endothelium and monocytes remain unclear. In this investigation, IL-38 treatment reduced THP-1 monocyte adhesion to HUVECs, decreased the expression of vascular adhesion molecules, and mitigated inflammation in the presence of palmitate. IL-38 treatment upregulated SIRT6 expression and enhanced autophagy markers such as LC3 conversion and p62 degradation. The effects of IL-38 were nullified by siRNA-mediated suppression of SIRT6 or heme oxygenase-1 (HO-1) in HUVECs and palmitate-treated THP-1 cells. These findings reveal that IL-38 mitigates inflammation through the SIRT6/HO-1 pathway, offering a potential therapeutic approach for addressing obesity-related atherosclerosis.


Assuntos
Aterosclerose , Sirtuínas , Humanos , Aterosclerose/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Inflamação/metabolismo , Interleucinas , Obesidade/complicações , Palmitatos , Sirtuínas/genética , Sirtuínas/metabolismo
4.
Biochem Biophys Res Commun ; 691: 149293, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38016337

RESUMO

CTRP4, identified as an adipokine, has demonstrated notable anti-inflammatory and anti-obesity effects in various disease models. Consequently, our research sought to explore the impact of CTRP4 on inflammation and the interaction between endothelial cells and monocytes in hyperlipidemic conditions. Using Western blotting, we assessed the expression levels of various proteins in HUVECs and THP-1 monocytes. Our study findings indicate that treatment with CTRP4 effectively mitigated the attachment of THP-1 monocytes to HUVECs. Furthermore, it reduced the expression of adhesion molecules and inflammation indicators in experimental cells exposed to hyperlipidemic conditions. Notably, CTRP4 treatment led to an increase in SIRT6 expression and the nuclear translocation of Nrf2. Interestingly, when SIRT6 or Nrf2 was silenced using siRNA, the positive effects of CTRP4 in HUVECs and THP-1 cells were nullified. Our results suggest that CTRP4 exhibits anti-inflammatory properties, thereby improving the interaction between endothelial cells and monocytes through the SIRT6/Nrf2-dependent pathway. This study provides insights into CTRP4 as a potential therapeutic target for mitigating obesity-related atherosclerosis.


Assuntos
Monócitos , Sirtuínas , Humanos , Monócitos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Adesão Celular , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Sirtuínas/metabolismo
5.
Biochem Biophys Res Commun ; 730: 150387, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39002201

RESUMO

Uvaol (UV), a pentacyclic triterpene found in olives and virgin olive oil, is known for its anti-inflammatory and antioxidant effects in various disease models. While olive oil is reported to reduce obesity and insulin resistance, the specific impact of UV on liver lipid metabolism and its molecular mechanisms are not fully understood. In this study, hepatic lipid accumulation was measured using oil red O staining, and protein expression levels in liver cells were assessed via Western blot analysis. Apoptosis was evaluated through cell viability and caspase 3 activity assays. UV treatment reduced lipid accumulation, fatty acid uptake, apoptosis, and ER stress in palmitate-treated liver cells. Additionally, UV enhanced fatty acid oxidation. Mechanistically, increased SIRT6 expression and autophagy were observed in UV-treated cells. SIRT6-targeted siRNA or 3-methyladenine blocked the effects of UV in hyperlipidemic cells. In conclusion, UV improves SIRT6/autophagy signaling, reducing lipid deposition and apoptosis in liver cells under high lipid conditions. This in vitro study provides strong evidence for potential therapeutic strategies for hepatic steatosis.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Hepatócitos , Hiperlipidemias , Metabolismo dos Lipídeos , Transdução de Sinais , Sirtuínas , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/efeitos da radiação , Metabolismo dos Lipídeos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hiperlipidemias/metabolismo , Hiperlipidemias/tratamento farmacológico , Sirtuínas/metabolismo , Sirtuínas/genética , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Autofagia/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Humanos , Animais , Triterpenos Pentacíclicos/farmacologia
6.
Biochem Biophys Res Commun ; 722: 150158, 2024 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-38795455

RESUMO

The cytokine interleukin-38 (IL-38), a recently discovered member of the IL-1 family, has been shown to regulate inflammation and improve hepatic endoplasmic reticulum stress and lipid metabolism in individuals with obesity. However, its impact on insulin signaling in skeletal muscle cells and the underlying mechanisms remain unclear. In vitro obesity models were established using palmitate treatment, and Western blot analysis was performed to assess target proteins. Commercial kits were used to measure glucose uptake in cultured myocytes. Our study showed that IL-38 treatment alleviated the impairment of insulin signaling, including IRS-1 and Akt phosphorylation, and increased glucose uptake in palmitate-treated C2C12 myocytes. Increased levels of STAT3-mediated signaling and oxidative stress were observed in these cells following palmitate treatment, and these effects were reversed by IL-38 treatment. In addition, IL-38 treatment upregulated the expression of PPARδ, SIRT1 and antioxidants. Knockdown of PPARδ or SIRT1 using appropriate siRNAs abrogated the effects of IL-38 on insulin signaling, oxidative stress, and the STAT3-dependent pathway. These results suggest that IL-38 alleviates insulin resistance by inhibiting STAT3-mediated signaling and oxidative stress in skeletal muscle cells through PPARδ/SIRT1. This study provides fundamental evidence to support the potential use of IL-38 as a safe therapeutic agent for the treatment of insulin resistance and type 2 diabetes.


Assuntos
Hiperlipidemias , Resistência à Insulina , Estresse Oxidativo , Fator de Transcrição STAT3 , Transdução de Sinais , Sirtuína 1 , Animais , Estresse Oxidativo/efeitos dos fármacos , Sirtuína 1/metabolismo , Sirtuína 1/genética , Fator de Transcrição STAT3/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Hiperlipidemias/metabolismo , Hiperlipidemias/tratamento farmacológico , PPAR delta/metabolismo , PPAR delta/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Interleucinas/metabolismo , Interleucinas/genética , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Interleucina-1/metabolismo , Interleucina-1/genética
7.
J Transl Med ; 22(1): 38, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195611

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. METHODS: We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. RESULTS: Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. CONCLUSIONS: Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.


Assuntos
Proteínas Quinases Ativadas por AMP , Degeneração Macular , Humanos , Caspase 3 , Tunicamicina/farmacologia , Fator A de Crescimento do Endotélio Vascular , Degeneração Macular/terapia , Miocinas , Células Epiteliais , Pigmentos da Retina
8.
Crit Rev Food Sci Nutr ; : 1-23, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230393

RESUMO

The increasing emphasis on the quality and safety of agricultural products, which are vital to global trade and consumer health, has driven the innovation of cost-effective, convenient, and rapid smart detection technologies. Smartphones, with their interdisciplinary functionalities, have become valuable tools in quantification and analysis research. Acting as portable, affordable, and user-friendly analytical devices, smartphones are equipped with high-resolution cameras, displays, memory, communication modules, sensors, and operating systems (Android or IOS), making them powerful, palm-sized remote computers. This review delves into how visual inspection technology and smartphones have enhanced the quality and safety of agricultural products over the past decade. It also evaluates the key features and limitations of existing smart rapid inspection methods for agricultural products and anticipates future advancements, offering insights into the application of smart rapid inspection technology in agriculture.

9.
Drug Resist Updat ; 71: 101005, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37647746

RESUMO

AIMS: Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer. METHODS: The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo. RESULTS: CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells. CONCLUSIONS: Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Animais , Camundongos , Neoplasias Pancreáticas/tratamento farmacológico , Cardiotoxicidade , Membrana Celular , Resistência a Múltiplos Medicamentos , Neoplasias Pancreáticas
10.
Chem Eng J ; 4912024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38882000

RESUMO

Immunoassays have been widely used to determine small-molecule compounds in food and the environment, meeting the challenge of obtaining false positive or negative results because of the variance in the batches of antibodies and antigens. To resolve this problem, atrazine (ATR) was used as a target, and anti-idiotypic nanobodies for ATR (AI-Nbs) and a recombinant full-length antibody against ATR (ATR-rAb) were prepared for the development of a sustainable enzyme-linked immunosorbent assay (ELISA). AI-Nb-7, AI-Nb-58, and AI-Nb-66 were selected from an immune phage display library. ATR-rAb was produced in mammalian HEK293 (F) cells. Among the four detection methods explored, the assay using AI-Nb-66 as a coating antigen and ATR-rAb as a detection reagent yielded a half maximal inhibitory concentration (IC50) of 1.66 ng mL-1 for ATR and a linear range of 0.35-8.73 ng mL-1. The cross-reactivity of the assay to ametryn was 64.24%, whereas that to terbutylazine was 38.20%. Surface plasmon resonance (SPR) analysis illustrated that these cross-reactive triazine compounds can bind to ATR-rAb to varying degrees at high concentrations; however, the binding/dissociation kinetic curves and the response values at the same concentration are different, which results in differences in cross-reactivity. Homology modeling and molecular docking revealed that the triazine ring is vital in recognizing triazine compounds. The proposed immunoassay exhibited acceptable recoveries of 84.40-105.36% for detecting fruit, vegetables, and black tea. In conclusion, this study highlights a new strategy for developing sustainable immunoassays for detecting trace pesticide contaminants.

11.
J Dairy Sci ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39343213

RESUMO

Cow milk, although rich in essential nutrients, is a well-known allergic food that can cause allergic reactions in infants and young children. ß-Lactoglobulin accounts for 10% of the total protein in milk and 50% of the whey protein, which has high nutritional value and excellent functional properties but is also the main allergen leading to milk protein allergy. Exploring the mechanism of milk allergy and selecting suitable separation and purification methods to obtain high-purity ß-Lactoglobulin is the premise of research on reducing allergenicity. In this review, the research progress in membrane technology, gel filtration chromatography, ion exchange chromatography, affinity chromatography, precipitation and aqueous 2-phase system separation for the separation and purification of milk ß-Lactoglobulin is reviewed in detail to promote the further development of milk ß-Lactoglobulin separation and purification methods and provide a new method for the development of hypoallergenic dairy products in the future. Among these methods, ion exchange chromatography and gel chromatography are widely used, precipitation is generally used as a crude purification step, and high-performance liquid chromatography and membrane technology are used for further purification to improve the purity of allergens.

12.
Mikrochim Acta ; 191(10): 631, 2024 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340568

RESUMO

A highly specific and sensitive rapid two-signal assay was developed for the detection of Salmonella typhimurium in foods of animal origin. The invA gene of Salmonella was used as the biorecognition element and recombinase-assisted amplification (RAA) technology for signal amplification. By utilizing the specific recognition and efficient trans-cleavage activity of CRISPR/Cas12a, point-of-care testing (POCT) for S. typhimurium was achieved via lateral flow strips (LFS) and personal glucometer (PGM) biosensors as dual signal readout systems, with sensitivities of 33 CFU/mL and 20 CFU/mL, respectively. Users can select the appropriate test system on the basis of specific application requirements: LFSs are ideal for rapid onsite screening, whereas glucometer biosensors offer precise quantitative determination. This approach simplifies the use of large instruments and overcomes site constraints, demonstrating good accuracy and applicability in animal-derived samples, with significant potential for the detection of other pathogens and for use in restricted environments.


Assuntos
Proteínas de Bactérias , Técnicas Biossensoriais , Sistemas CRISPR-Cas , Microbiologia de Alimentos , Salmonella typhimurium , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Animais , Salmonella typhimurium/isolamento & purificação , Salmonella typhimurium/genética , Proteínas de Bactérias/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Proteínas Associadas a CRISPR/genética , Limite de Detecção , Contaminação de Alimentos/análise , Endodesoxirribonucleases , Recombinases/metabolismo , Testes Imediatos
13.
J Cell Physiol ; 238(5): 966-975, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36890751

RESUMO

Gremlin-1 (GR1) is a novel adipokine that is highly expressed in human adipocytes and has been shown to inhibit the BMP2/4-TGFb signaling pathway. It has an effect on insulin sensitivity. Elevated levels of Gremlin have been shown to lead to insulin resistance in skeletal muscle, adipocytes, and hepatocytes. In this study, we investigated the effect of GR1 on hepatic lipid metabolism under hyperlipidemic conditions and explored the molecular mechanisms associated with GR1 by in vitro and in vivo studies. We found that palmitate increased GR1 expression in visceral adipocytes. Recombinant GR1 increased lipid accumulation, lipogenesis, and ER stress markers in cultured primary hepatocytes. Treatment with GR1 increased EGFR expression and mTOR phosphorylation and reduced autophagy markers. EGFR or rapamycin siRNA reduced the effects of GR1 on lipogenic lipid deposition and ER stress in cultured hepatocytes. Administration of GR1 via the tail vein induced lipogenic proteins and ER stress while suppressing autophagy in the livers of experimental mice. Suppression of GR1 by in vivo transfection reduced the effects of a high-fat diet on hepatic lipid metabolism, ER stress, and autophagy in mice. These results suggest that the adipokine GR1 promotes hepatic ER stress due to the impairment of autophagy, ultimately causing hepatic steatosis in the obese state. The current study demonstrated that targeting GR1 may be a potential therapeutic approach for treating metabolic diseases, including metabolic-associated fatty liver disease (MAFLD).


Assuntos
Adipocinas , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Adipocinas/metabolismo , Autofagia , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático , Receptores ErbB/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos/farmacologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Transdução de Sinais/genética , Regulação para Cima
14.
Biochem Biophys Res Commun ; 682: 104-110, 2023 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-37806247

RESUMO

Hyperglycemia, characterized by high blood glucose levels resulting from pancreatic beta cell dysfunction or impaired insulin signaling, is a contributing factor in the development of diabetic nephropathy. This study aimed to investigate the effects of C1q/TNF-related protein 4 (CTRP4), known for its anti-obesity and anti-inflammatory properties in various disease models, on podocyte apoptosis and endoplasmic reticulum (ER) stress in the presence of elevated glucose levels. The expression levels of various proteins in podocytes and adipocytes were evaluated by Western blotting. Autophagosomes in podocytes were stained by MDC. Chromatin condensation in podocytes was examined by Hoechst staining. The research revealed increased expression of CTRP4 in 3T3-L1 adipocytes and CIHP-1 podocytes exposed to high glucose (HG) conditions. Treatment with CTRP4 effectively mitigated HG-induced apoptosis and ER stress and normalized epithelial-to-mesenchymal transition (EMT) markers in CIHP-1 cells. Furthermore, elevated levels of AMPK phosphorylation and autophagy were observed in CIHP-1 cells treated with CTRP4. Silencing of AMPK or the use of 3-methyl adenine (3 MA) reduced the impacts of CTRP4 on apoptosis, EMT markers and ER stress in CIHP-1 cells. In conclusion, these findings suggest that CTRP4 alleviates ER stress in podocytes under hyperglycemic conditions, leading to the suppression of apoptosis and the restoration of EMT through AMPK/autophagy-mediated signaling. These insights provide valuable information for the development of therapeutic strategies for diabetic nephropathy.


Assuntos
Nefropatias Diabéticas , Podócitos , Humanos , Podócitos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal , Apoptose , Autofagia , Glucose/farmacologia , Glucose/metabolismo
15.
Biochem Biophys Res Commun ; 642: 113-117, 2023 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-36566562

RESUMO

Musclin (MUS), an exercise-responsive myokine, has been documented to attenuate inflammation and enhance physical endurance. However, the effects of MUS on differentiation and related molecular mechanisms in adipocytes have not yet been studied. In this study, we found that treatment with MUS attenuated lipid accumulation in fully differentiated 3T3-L1 cells. Furthermore, MUS treatment enhanced lipolysis assessed by glycerol release, and caused apoptosis, whereas it reduced the expression of lipogenic proteins, such as PPARγ and processed SREBP1. Treatment with MUS augmented phosphorylated PKA expression, whereas suppressed p38 phosphorylation in 3T3-L1 adipocytes. H89, a selective PKA inhibitor reduced the effects of MUS on lipogenic lipid accumulation as well as lipolysis except for apoptosis. These results suggest that MUS promotes lipolysis and suppresses lipogenesis through a PKA/p38-dependent pathway, thereby ameliorating lipid deposition in cultured adipocytes. The current study offers the potential of MUS as a therapeutic approach for treating obesity with few side effects.


Assuntos
Lipogênese , Lipólise , Animais , Camundongos , Células 3T3-L1 , Regulação para Cima , Adipócitos/metabolismo , Lipídeos/farmacologia , Adipogenia
16.
Biochem Biophys Res Commun ; 648: 59-65, 2023 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-36736092

RESUMO

Oroxylin-A (OA) is an O-methylated flavone that has been demonstrated to have anti-inflammatory properties in various disease models. However, the roles of OA in hepatic lipid metabolism and the specific molecular mechanisms by which it exerts these effects are not yet fully understood. In the current study, we aimed to investigate the effects of OA on hepatic lipid deposition and apoptosis, which play a pivotal role in the development of nonalcoholic fatty liver disease (NAFLD) in obesity in vitro models. We found that treatment with OA attenuated lipid accumulation, the expression of lipogenesis-associated proteins and apoptosis in palmitate-treated primary mouse hepatocytes. OA treatment suppressed phosphorylated NFκB and IκB expression in as well as TNFα and MCP-1 release from hepatocytes treated with palmitate. Treatment of hepatocytes with OA augmented AMPK phosphorylation and FGF21 expression. siRNA of AMPK or FGF21 abolished the effects of OA on inflammation as well as lipid accumulation and apoptosis in hepatocytes under palmitate treatment conditions. In conclusion, OA improves inflammation through the AMPK/FGF21 pathway, thereby attenuating lipid accumulation and apoptosis in hepatocytes. This study may help identify new targets for developing treatments for NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Fígado/metabolismo , Hepatócitos/metabolismo , Metabolismo dos Lipídeos , Inflamação/metabolismo , Palmitatos/farmacologia , Palmitatos/metabolismo , Apoptose , Camundongos Endogâmicos C57BL
17.
Biochem Biophys Res Commun ; 658: 62-68, 2023 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-37023616

RESUMO

Musclin, an exercise-responsive myokine, has the ability to attenuate inflammation, oxidative stress, and apoptosis in cardiomyocytes under pathogenic conditions. While the potential benefits of musclin in the cardiovascular system have been well documented, its effects on hepatic endoplasmic reticulum (ER) stress and lipid metabolism are not fully understood. The present study showed that musclin treatment reduced lipid accumulation and lipogenic protein expression in primary hepatocytes exposed to palmitate. Palmitate treatment led to an increase in markers of ER stress, which was reversed by musclin treatment. Musclin treatment increased SIRT7 expression and markers of autophagy in a dose-dependent manner. Small interfering (si) RNA of SIRT7 or 3-methyladenine (3 MA) reduced the effects of musclin on lipogenic lipid deposition in hepatocytes under hyperlipidemic conditions. These findings suggest that musclin can suppress palmitate-induced ER stress by upregulating SIRT7 and autophagy signaling, thereby alleviating lipid accumulation in primary hepatocytes. The current study provides a potential therapeutic strategy for the treatment of liver diseases characterized by lipid accumulation and ER stress, such as nonalcoholic fatty liver disease (NAFLD).


Assuntos
Hepatopatia Gordurosa não Alcoólica , Sirtuínas , Humanos , Hepatócitos/metabolismo , Fígado/metabolismo , Estresse do Retículo Endoplasmático , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metabolismo dos Lipídeos , Autofagia , Palmitatos/farmacologia , Palmitatos/metabolismo , Sirtuínas/metabolismo
18.
Phytochem Rev ; 22(1): 275-308, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36345415

RESUMO

There are approximately 260 known species in the genus Millettia, many of which are used in traditional medicine to treat human and other animal ailments in various parts of the world. Being in the Leguminosae (Fabaceae) family, Millettia species are rich sources of isoflavonoids. In the past three decades alone, several isoflavonoids originating from Millettia have been isolated, and their pharmacological activities have been evaluated against major diseases, such as cancer, inflammation, and diabetes. Despite such extensive research, no recent and comprehensive review of the phytochemistry and pharmacology of Millettia isoflavonoids is available. Furthermore, the structural diversity of isoflavonoids in Millettia species has rarely been reported. In this review, we comprehensively summarized the structural diversity of Millettia isoflavonoids, the methods used for their extraction and isolation protocols, and their pharmacological properties. According to the literature, 154 structurally diverse isoflavonoids were isolated and reported from the various tissues of nine well-known Millettia species. Prenylated isoflavonoids and rotenoids were the most dominant subclasses of isoflavonoids reported. Other subclasses of reported isoflavonoids include isoflavans, aglycone isoflavones, glycosylated isoflavones, geranylated isoflavonoids, phenylcoumarins, pterocarpans and coumaronochromenes. Although some isolated molecules showed promising pharmacological properties, such as anticancer, anti-inflammatory, estrogenic, and antibacterial activities, others remained untested. In general, this review highlights the potential of Millettia isoflavonoids and could improve their utilization in drug discovery and medicinal use processes. Supplementary Information: The online version contains supplementary material available at 10.1007/s11101-022-09845-w.

19.
Crit Rev Food Sci Nutr ; 63(21): 4942-4965, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34852703

RESUMO

Excessive use of pesticides can cause contamination of the environment and agricultural products that are directly threatening human life and health. Therefore, in the process of food safety supervision, it is crucial to conduct sensitive and rapid detection of pesticide residues. The recognition element is the vital component of sensors and methods for fast testing pesticide residues in food. Improper recognition elements may lead to defects of testing methods, such as poor stability, low sensitivity, high economic costs, and waste of time. We can use the molecular biological technique to address these challenges as a good strategy for recognition element production and modification. Herein, we review the molecular biological methods of five specific recognition elements, including aptamers, genetic engineering antibodies, DNAzymes, genetically engineered enzymes, and whole-cell-based biosensors. In addition, the application of these identification elements combined with biosensor and immunoassay methods in actual detection was also discussed. The purpose of this review was to provide a valuable reference for further development of rapid detection methods for pesticide residues.


Assuntos
Técnicas Biossensoriais , Resíduos de Praguicidas , Praguicidas , Humanos , Praguicidas/análise , Resíduos de Praguicidas/análise , Contaminação de Alimentos/análise , Inocuidade dos Alimentos , Técnicas Biossensoriais/métodos
20.
Crit Rev Food Sci Nutr ; 63(31): 10880-10898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35648034

RESUMO

Sample pretreatment is essential for trace analysis of pesticides in complex food and environment matrices. Recently, organic-inorganic hybrid materials have gained increasing attention in pesticide extraction and preconcentration. This review highlighted the common organic-inorganic hybrid materials used as absorbents in sample pretreatment for pesticide detection. Furthermore, the preparation and characterization of organic-inorganic hybrid materials were summarized. To obtain a deep understanding of adsorption toward target analytes, the adsorption mechanism and absorption evaluation were discussed. Finally, the applications of organic-inorganic hybrid materials in sample pretreatment techniques and perspectives in the future are also discussed.


Assuntos
Praguicidas , Praguicidas/análise , Extração em Fase Sólida/métodos , Adsorção
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