Biochemical and biophysical research communications最新文献_第9页

2-Methoxy-4-vinylphenol mitigates malignancy of cholangiocarcinoma cells through the blockade of sonic hedgehog signalling

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-21 DOI: 10.1016/j.bbrc.2025.151515

Jungwhoi Lee , Nur Azizah Arryanie Binti Morshidi , Jungsul Lee , Woogwang Sim , Jae-Hoon Kim

Background

Cholangiocarcinoma (CCA) is one of the most refractory malignancies with a grave prognosis. 2-Methoxy-4-vinylpenol (2M4VP) is a well-known flavonoid having beneficial functions in human health including an anti-cancer effect in various malignant tumours. However, the anti-cancer effect of 2M4VP against CCA remains ambiguous.

Purpose

The present study aimed to investigate the bio-activity of 2M4VP in human CCA.

Methods

Biological activities of 2M4VP were examined using in vitro assays. Prognostic values were assessed using Kaplan-Meier and Liptak's z score analyses.

Results

2M4VP significantly attenuated the anti-migratory features of CCA cells when compared to human intrahepatic bile duct epithelial cells (HIBEpiC), but not in viability. The anti-cancer effect of 2M4VP was induced by down-regulating the expression of cellular sonic hedgehog (Shh) signalling molecule such as GLI family zinc finger 3 (GLI3). In addition, 2M4VP treatment evoked a synergic anti-cancer effect when used in combination with gemcitabine. Furthermore, high GLI3 expression was significantly associated with a poor prognosis in patients with CCA.

Conclusions

These results collectively indicate that 2M4VP might be a natural reagent against CCA metastasis, functioning through the ablating Shh signalling associated GLI3 expression, which provides the rationale for further investigation and a potential clinical trial using 2M4VP against CCA.

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引用次数: 0

Muscle cells affect the promoting effect of FGF21 on lipid accumulation in porcine adipocytes through AhR/FGFR1 signaling pathway

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-21 DOI: 10.1016/j.bbrc.2025.151520

Shengda Qiu, Xiaolei Ding, Xiangfei Ma, Lifan Zhang, Jie Chen, Wei Wei

The intramuscular fat (IMF) content, as an important meat quality trait, can directly affect the tenderness, juiciness, and flavor of pork. Reasonably increasing the IMF content can improve the palatability of pork. Therefore, identification of important factors for the lipid accumulation among muscles is the breakthrough point for improving meat quality. FGF21, identified as a novel metabolic regulator, has been found to regulate glucose and lipid metabolism in 3T3-L1 adipocytes, but its function in porcine adipocytes remains unclear. In this study, we discovered that the administration of recombinant FGF21 protein promotes adipogenic differentiation and increases triglyceride accumulation in porcine adipocytes. While the expression of FGFR1 in adipocytes under muscle conditions is inhibited, affecting the signal transduction of FGF21. This inhibitory effect is accompanied by activation of the AhR signaling pathway. When treated with the AhR antagonist CH223191, there was a partial restoration of FGFR1 expression levels. This indicates that muscle cells suppress the expression of FGFR1 in adipocytes by activating the AhR signaling pathway, thereby affecting the signal transduction of FGF21. Our results reveal the regulatory role of FGF21 in pig adipocyte differentiation and the regulatory mechanism of muscle environment on FGFR1 expression, providing new theoretical basis for IMF content improvement from the perspective of FGF21-FGFR1 signaling transduction.

{"title":"Muscle cells affect the promoting effect of FGF21 on lipid accumulation in porcine adipocytes through AhR/FGFR1 signaling pathway","authors":"Shengda Qiu, Xiaolei Ding, Xiangfei Ma, Lifan Zhang, Jie Chen, Wei Wei","doi":"10.1016/j.bbrc.2025.151520","DOIUrl":"10.1016/j.bbrc.2025.151520","url":null,"abstract":"<div><div>The intramuscular fat (IMF) content, as an important meat quality trait, can directly affect the tenderness, juiciness, and flavor of pork. Reasonably increasing the IMF content can improve the palatability of pork. Therefore, identification of important factors for the lipid accumulation among muscles is the breakthrough point for improving meat quality. FGF21, identified as a novel metabolic regulator, has been found to regulate glucose and lipid metabolism in 3T3-L1 adipocytes, but its function in porcine adipocytes remains unclear. In this study, we discovered that the administration of recombinant FGF21 protein promotes adipogenic differentiation and increases triglyceride accumulation in porcine adipocytes. While the expression of FGFR1 in adipocytes under muscle conditions is inhibited, affecting the signal transduction of FGF21. This inhibitory effect is accompanied by activation of the AhR signaling pathway. When treated with the AhR antagonist CH223191, there was a partial restoration of FGFR1 expression levels. This indicates that muscle cells suppress the expression of FGFR1 in adipocytes by activating the AhR signaling pathway, thereby affecting the signal transduction of FGF21. Our results reveal the regulatory role of FGF21 in pig adipocyte differentiation and the regulatory mechanism of muscle environment on FGFR1 expression, providing new theoretical basis for IMF content improvement from the perspective of FGF21-FGFR1 signaling transduction.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151520"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ITGA8 deficiency in hepatic stellate cells attenuates CCl4-Induced liver fibrosis via suppression of COL11A1

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-21 DOI: 10.1016/j.bbrc.2025.151522

Xuzhen Yan , Qi Han , Wenyue Wu , Hong Li , Wen Zhang , Yiwen Wang , Wei Chen , Aiting Yang , Hong You

Background and objective

Liver fibrosis is a pathological process driven by chronic liver injury, characterized by excessive extracellular matrix (ECM) deposition due to hepatic stellate cell (HSC) activation. Integrins are critical regulators of ECM remodeling and HSC activation, yet the role of integrin α8(ITGA8) in liver fibrosis remains unclear. This study aims to investigate the function and underlying mechanisms of HSC-derived ITGA8 in liver fibrosis and evaluate the therapeutic potential of ITGA8-targeted intervention.

Methods

A CCl₄-induced mouse liver fibrosis model and public database analysis were used to assess ITGA8 expression and localization in liver fibrosis. AAV2/6-shItga8 was utilized to selectively silence HSC-derived ITGA8, and its effects on HSC activation and ECM accumulation were examined. In addition, in vitro ITGA8 knockdown combined with proteomic analysis was performed to explore the molecular mechanisms linking ITGA8 to ECM remodeling.

Results

ITGA8 expression was significantly upregulated in fibrotic liver tissues across different etiologies, with a strong colocalization with HSCs. Silencing ITGA8 using AAV2/6-shItga8 effectively reduced liver fibrosis, as indicated by decreased hepatic inflammation, lower serum ALT levels, reduced inflammatory cell infiltration, and downregulated expression of pro-inflammatory cytokines. Fibrosis markers, including Sirius Red staining, type I collagen deposition, and α-SMA expression, were all reduced upon Itga8 silencing. Proteomic analysis revealed that ITGA8 regulates liver fibrosis through the ECM-receptor interaction pathway, with COL11A1 identified as a key downstream target. ITGA8 knockdown significantly suppressed COL11A1 expression, and reduced HSC-mediated collagen contraction, suggesting that ITGA8 contributes to ECM cross-linking and fibrosis progression via COL11A1 regulation.

Conclusion

This study demonstrates that HSC-derived ITGA8 promotes ECM accumulation and liver fibrosis progression by regulating COL11A1. Targeted silencing of ITGA8 via AAV2/6-shItga8 effectively alleviates liver fibrosis, providing new insights into ITGA8 as a potential therapeutic target for antifibrotic treatment.

{"title":"ITGA8 deficiency in hepatic stellate cells attenuates CCl4-Induced liver fibrosis via suppression of COL11A1","authors":"Xuzhen Yan , Qi Han , Wenyue Wu , Hong Li , Wen Zhang , Yiwen Wang , Wei Chen , Aiting Yang , Hong You","doi":"10.1016/j.bbrc.2025.151522","DOIUrl":"10.1016/j.bbrc.2025.151522","url":null,"abstract":"<div><h3>Background and objective</h3><div>Liver fibrosis is a pathological process driven by chronic liver injury, characterized by excessive extracellular matrix (ECM) deposition due to hepatic stellate cell (HSC) activation. Integrins are critical regulators of ECM remodeling and HSC activation, yet the role of integrin α8(ITGA8) in liver fibrosis remains unclear. This study aims to investigate the function and underlying mechanisms of HSC-derived ITGA8 in liver fibrosis and evaluate the therapeutic potential of ITGA8-targeted intervention.</div></div><div><h3>Methods</h3><div>A CCl<sub>4</sub>-induced mouse liver fibrosis model and public database analysis were used to assess ITGA8 expression and localization in liver fibrosis. AAV2/6-shItga8 was utilized to selectively silence HSC-derived ITGA8, and its effects on HSC activation and ECM accumulation were examined. In addition, in vitro ITGA8 knockdown combined with proteomic analysis was performed to explore the molecular mechanisms linking ITGA8 to ECM remodeling.</div></div><div><h3>Results</h3><div>ITGA8 expression was significantly upregulated in fibrotic liver tissues across different etiologies, with a strong colocalization with HSCs. Silencing ITGA8 using AAV2/6-shItga8 effectively reduced liver fibrosis, as indicated by decreased hepatic inflammation, lower serum ALT levels, reduced inflammatory cell infiltration, and downregulated expression of pro-inflammatory cytokines. Fibrosis markers, including Sirius Red staining, type I collagen deposition, and α-SMA expression, were all reduced upon <em>Itga8</em> silencing. Proteomic analysis revealed that ITGA8 regulates liver fibrosis through the ECM-receptor interaction pathway, with COL11A1 identified as a key downstream target. ITGA8 knockdown significantly suppressed COL11A1 expression, and reduced HSC-mediated collagen contraction, suggesting that ITGA8 contributes to ECM cross-linking and fibrosis progression via COL11A1 regulation.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that HSC-derived ITGA8 promotes ECM accumulation and liver fibrosis progression by regulating COL11A1. Targeted silencing of ITGA8 via AAV2/6-shItga8 effectively alleviates liver fibrosis, providing new insights into ITGA8 as a potential therapeutic target for antifibrotic treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"756 ","pages":"Article 151522"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts 骨蛋白激酶受转化生长因子-β1 的诱导，并调节人类真皮成纤维细胞的促纤维化反应

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-21 DOI: 10.1016/j.bbrc.2025.151524

Aaron K. McDowell-Sanchez , Alan R. Waich Cohen , Santiago Sanchez , Konstantin Tsoyi

Transforming growth factor-beta1 (TGF-β1) is known to play a key role in the progression of organ fibrosis. Here, we demonstrate that TGF-β1 induces osteoprotegerin (OPG) expression in human dermal fibroblasts (HDFs) at both protein and mRNA levels. OPG neutralization has led to attenuation of TGF-β1-mediated profibrotic effects in HDFs. Further, we found that recombinant OPG induced fibronectin (FN) production and alpha-smooth muscle actin (α-SMA) expression. Interestingly, the OPG-mediated effect was significantly attenuated by αvβ3-integrin inhibitors (cyclo(RGDfK) and cilengitide) suggesting that OPG exerts profibrotic responses in human dermal fibroblasts by regulating αvβ3-integrin activation. Taken together, our data suggest that OPG expression is stimulated by TGF-β1 and contributes to dermal fibroblast activation.

引用次数: 0

Soluble DPP4 promotes hepatocyte lipid accumulation via SOX2-SCD1 signaling and counteracts DPP4 inhibition

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-21 DOI: 10.1016/j.bbrc.2025.151521

Chen Shen , Ha Ram Oh , Young Ran Park , Shinyoung Oh , Ji Hyun Park

Dipeptidyl peptidase-4 (DPP4), a well-known target of antidiabetic therapy, is implicated in steatotic liver disease. However, its role in hepatic lipid metabolism, particularly the distinct functions of soluble DPP4 (sDPP4) and membrane-bound DPP4 (mbDPP4), remains unclear. Here, we identify SOX2 as a key mediator linking sDPP4 to hepatocyte lipid accumulation, uncovering a previously unreported regulatory mechanism. sDPP4 promotes free fatty acid (FFA)-induced lipid accumulation and triglyceride (TG) synthesis in hepatocytes by upregulating SOX2, a stemness-associated transcription factor. SOX2 induction increased the expression of stearoyl-coenzyme A desaturase 1 (SCD1), a key lipogenic enzyme, supporting the role of SOX2-SCD1 signaling in sDPP4-mediated hepatic steatosis. SOX2 silencing abolished these effects, confirming its requirement for sDPP4-induced lipid accumulation. Similarly, mbDPP4 overexpression increased FFA-induced lipid synthesis and SOX2 expression, while its knockdown suppressed these responses. Pharmacological inhibition of mbDPP4 activity reduced lipid accumulation and downregulated SOX2, SCD1, and fatty acid synthase expression. However, exogenous sDPP4 reversed these effects, counteracting the lipid-suppressing effect of DPP4 inhibition. In vivo, high-fat diet (HFD)-fed mice exhibited increased plasma sDPP4 levels, whereas hepatic mbDPP4 expression remained unchanged. This correlated with enhanced hepatic SOX2 expression, suggesting that elevated sDPP4 may contribute to hepatic lipid accumulation independent of mbDPP4 activity. Collectively, our findings highlight the role of sDPP4-SOX2 signaling in hepatic lipid accumulation and underscore the need to distinguish sDPP4 from mbDPP4 in steatotic liver disease. Targeting the sDPP4-SOX2 axis could be explored as a potential therapeutic approach for steatotic liver disease.

{"title":"Soluble DPP4 promotes hepatocyte lipid accumulation via SOX2-SCD1 signaling and counteracts DPP4 inhibition","authors":"Chen Shen , Ha Ram Oh , Young Ran Park , Shinyoung Oh , Ji Hyun Park","doi":"10.1016/j.bbrc.2025.151521","DOIUrl":"10.1016/j.bbrc.2025.151521","url":null,"abstract":"<div><div>Dipeptidyl peptidase-4 (DPP4), a well-known target of antidiabetic therapy, is implicated in steatotic liver disease. However, its role in hepatic lipid metabolism, particularly the distinct functions of soluble DPP4 (sDPP4) and membrane-bound DPP4 (mbDPP4), remains unclear. Here, we identify SOX2 as a key mediator linking sDPP4 to hepatocyte lipid accumulation, uncovering a previously unreported regulatory mechanism. sDPP4 promotes free fatty acid (FFA)-induced lipid accumulation and triglyceride (TG) synthesis in hepatocytes by upregulating SOX2, a stemness-associated transcription factor. SOX2 induction increased the expression of stearoyl-coenzyme A desaturase 1 (SCD1), a key lipogenic enzyme, supporting the role of SOX2-SCD1 signaling in sDPP4-mediated hepatic steatosis. SOX2 silencing abolished these effects, confirming its requirement for sDPP4-induced lipid accumulation. Similarly, mbDPP4 overexpression increased FFA-induced lipid synthesis and SOX2 expression, while its knockdown suppressed these responses. Pharmacological inhibition of mbDPP4 activity reduced lipid accumulation and downregulated SOX2, SCD1, and fatty acid synthase expression. However, exogenous sDPP4 reversed these effects, counteracting the lipid-suppressing effect of DPP4 inhibition. In vivo, high-fat diet (HFD)-fed mice exhibited increased plasma sDPP4 levels, whereas hepatic mbDPP4 expression remained unchanged. This correlated with enhanced hepatic SOX2 expression, suggesting that elevated sDPP4 may contribute to hepatic lipid accumulation independent of mbDPP4 activity. Collectively, our findings highlight the role of sDPP4-SOX2 signaling in hepatic lipid accumulation and underscore the need to distinguish sDPP4 from mbDPP4 in steatotic liver disease. Targeting the sDPP4-SOX2 axis could be explored as a potential therapeutic approach for steatotic liver disease.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"756 ","pages":"Article 151521"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of exosomes in diagnosis, pathophysiology, and management of Alzheimer's Disease

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-21 DOI: 10.1016/j.bbrc.2025.151526

Rajni Daksh , Meby Susan Mathew , Aan Mery Bosco , Christy Sojan , Antriya Annie Tom , Sree Lalitha Bojja , Madhavan Nampoothiri

Alzheimer's disease (AD) is a neurodegenerative disorder associated with impaired cognitive function and memory loss. Currently, available therapeutics can effectively alleviate the symptoms of AD, but there is a lack of treatment to halt the progression of the disease. In recent years, exosomes have gained much attention due to their involvement in various neurological disorders. Exosomes are small extracellular vesicles comprising lipids, proteins, DNA, non-coding RNA, and mRNAs, can carry various therapeutic molecules, and are potential drug delivery vehicles. Exosomes are known as a double-edged sword due to their involvement in both the pathogenesis and management of AD. This review explores the function of exosomes in the pathophysiology, treatment, and diagnosis of AD, also emphasizing their potential as a targeted drug delivery carrier to the brain. This review seeks to provide novel perspectives to understand better the onset, targeted treatment, and diagnosis of AD using exosomes.

{"title":"The role of exosomes in diagnosis, pathophysiology, and management of Alzheimer's Disease","authors":"Rajni Daksh , Meby Susan Mathew , Aan Mery Bosco , Christy Sojan , Antriya Annie Tom , Sree Lalitha Bojja , Madhavan Nampoothiri","doi":"10.1016/j.bbrc.2025.151526","DOIUrl":"10.1016/j.bbrc.2025.151526","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disorder associated with impaired cognitive function and memory loss. Currently, available therapeutics can effectively alleviate the symptoms of AD, but there is a lack of treatment to halt the progression of the disease. In recent years, exosomes have gained much attention due to their involvement in various neurological disorders. Exosomes are small extracellular vesicles comprising lipids, proteins, DNA, non-coding RNA, and mRNAs, can carry various therapeutic molecules, and are potential drug delivery vehicles. Exosomes are known as a double-edged sword due to their involvement in both the pathogenesis and management of AD. This review explores the function of exosomes in the pathophysiology, treatment, and diagnosis of AD, also emphasizing their potential as a targeted drug delivery carrier to the brain. This review seeks to provide novel perspectives to understand better the onset, targeted treatment, and diagnosis of AD using exosomes.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151526"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lectin-like oxidized low-density lipoprotein receptor-1 reduces 5-FU sensitivity in gastric cancer cells via JAK/STAT/NOX4 axis

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-20 DOI: 10.1016/j.bbrc.2025.151519

Lanxin Wang, Gaofei He, Kangwei Qi, Long Yu, Di Kong, Jianxin Gu, Lan Wang

5-Fluorouracil (5-FU) is the primary chemotherapeutic agent for the clinical management of advanced gastric cancer (GC). However, the emergence of drug resistance remains an inescapable challenge. In drug-resistant cancer cells, prior treatments contribute to elevated oxidative stress, resulting in higher level of reactive oxygen species (ROS) compared to treatment-naïve cancer cells. Activation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been shown to promote ROS production and facilitate epithelial-mesenchymal transition in GC. In this study, we found that LOX-1 silencing significantly increased 5-FU sensitivity by reducing tumor cell viability and colony-forming ability. Enrichment analysis suggested that nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) might act as a downstream effector of LOX-1, and overexpression of NOX4 was able to counteract the increased sensitivity to 5-FU induced by LOX-1 depletion. Additionally, bioinformatic predictions and in vitro experiments indicated that LOX-1 regulated NOX4 expression through JAK2/STAT3 signaling pathway. Altogether, this study provides novel evidence that LOX-1 mediated JAK2/STAT3/NOX4 axis plays a crucial role in modulating 5-FU sensitivity of GC and targeting LOX-1 may offer a promising therapeutic strategy to enhance the efficacy of 5-FU in advanced gastric cancer treatment.

{"title":"Lectin-like oxidized low-density lipoprotein receptor-1 reduces 5-FU sensitivity in gastric cancer cells via JAK/STAT/NOX4 axis","authors":"Lanxin Wang, Gaofei He, Kangwei Qi, Long Yu, Di Kong, Jianxin Gu, Lan Wang","doi":"10.1016/j.bbrc.2025.151519","DOIUrl":"10.1016/j.bbrc.2025.151519","url":null,"abstract":"<div><div>5-Fluorouracil (5-FU) is the primary chemotherapeutic agent for the clinical management of advanced gastric cancer (GC). However, the emergence of drug resistance remains an inescapable challenge. In drug-resistant cancer cells, prior treatments contribute to elevated oxidative stress, resulting in higher level of reactive oxygen species (ROS) compared to treatment-naïve cancer cells. Activation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been shown to promote ROS production and facilitate epithelial-mesenchymal transition in GC. In this study, we found that LOX-1 silencing significantly increased 5-FU sensitivity by reducing tumor cell viability and colony-forming ability. Enrichment analysis suggested that nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) might act as a downstream effector of LOX-1, and overexpression of NOX4 was able to counteract the increased sensitivity to 5-FU induced by LOX-1 depletion. Additionally, bioinformatic predictions and <em>in vitro</em> experiments indicated that LOX-1 regulated NOX4 expression through JAK2/STAT3 signaling pathway. Altogether, this study provides novel evidence that LOX-1 mediated JAK2/STAT3/NOX4 axis plays a crucial role in modulating 5-FU sensitivity of GC and targeting LOX-1 may offer a promising therapeutic strategy to enhance the efficacy of 5-FU in advanced gastric cancer treatment.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"753 ","pages":"Article 151519"},"PeriodicalIF":2.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PARP-2 acts on ILK signaling and pharmacological targeting of PARP-2 ameliorate endometriosis in a mouse model

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-20 DOI: 10.1016/j.bbrc.2025.151509

Satish Gupta , Rupal Tripathi , Ajay K. Kawale , Sudarsan Sarkar , Akanksha Singh , Raj Kumar Verma , Pushp Lata Sankhwar , Vanisha Sharma , Rajesh Kumar Jha

Endometriosis, an endocrine disorder in reproductive-aged women with an occurrence of ∼10 %, gives rise to inflammation, pelvic pain, menstrual irregularity, infertility, etc. One study demonstrated the elevated plasma level of PARP during endometriosis. Thus, we studied the role of PARP-2 during endometriosis using human endometriotic tissue and cells along with an endometriosis mouse model. We found an increased expression level of PARP-2 in the endometriotic tissue from human endometriosis patients, likewise in the endometriotic cells, 12Z and mouse model. The expression level of PARP-2 was suppressed by progesterone (P4) in the immortalized human endometriotic cells (IHECs). However, the danazol (100 mg/kg body weight) treatment reduced the lesion size, but not the expression level of PARP-2 in the endometriotic lesion from the mouse model. PARP-2 inhibition by UPF-1069 (5 mg/kg b. wt.) treatment in the mouse model of endometriosis reduced the endometriotic lesion area. During ovulation and letrozole (1 mg/kg b.wt.) treatment in the endometriosis SD rat model, the expression level of PARP-2 was high. The cell aggregation, a spheroid formation assay using IHECs was reduced by PARP-2 inhibition. The inflammatory chemokines, CCL-11 and -22, GSK-3beta and ILK were downregulated in IHECs by PARP-2 inhibitor (10 μM). Transient overexpression of ILK in endometriotic cells showed reduced levels of PARP-2 and GSK-3beta. In conclusion, PARP-2 is upregulated in the endometriotic tissue in response to estradiol (E2) and inhibition of it pharmacologically reduced the IHECs congregation and the endometriotic lesion, possibly affecting the inflammatory response via ILK-GSK-3beta, in the mouse model and human endometriotic cells.

{"title":"PARP-2 acts on ILK signaling and pharmacological targeting of PARP-2 ameliorate endometriosis in a mouse model","authors":"Satish Gupta , Rupal Tripathi , Ajay K. Kawale , Sudarsan Sarkar , Akanksha Singh , Raj Kumar Verma , Pushp Lata Sankhwar , Vanisha Sharma , Rajesh Kumar Jha","doi":"10.1016/j.bbrc.2025.151509","DOIUrl":"10.1016/j.bbrc.2025.151509","url":null,"abstract":"<div><div>Endometriosis, an endocrine disorder in reproductive-aged women with an occurrence of ∼10 %, gives rise to inflammation, pelvic pain, menstrual irregularity, infertility, etc. One study demonstrated the elevated plasma level of PARP during endometriosis. Thus, we studied the role of PARP-2 during endometriosis using human endometriotic tissue and cells along with an endometriosis mouse model. We found an increased expression level of PARP-2 in the endometriotic tissue from human endometriosis patients, likewise in the endometriotic cells, 12Z and mouse model. The expression level of PARP-2 was suppressed by progesterone (P4) in the immortalized human endometriotic cells (IHECs). However, the danazol (100 mg/kg body weight) treatment reduced the lesion size, but not the expression level of PARP-2 in the endometriotic lesion from the mouse model. PARP-2 inhibition by UPF-1069 (5 mg/kg b. wt.) treatment in the mouse model of endometriosis reduced the endometriotic lesion area. During ovulation and letrozole (1 mg/kg b.wt.) treatment in the endometriosis SD rat model, the expression level of PARP-2 was high. The cell aggregation, a spheroid formation assay using IHECs was reduced by PARP-2 inhibition. The inflammatory chemokines, CCL-11 and -22, GSK-3beta and ILK were downregulated in IHECs by PARP-2 inhibitor (10 μM). Transient overexpression of ILK in endometriotic cells showed reduced levels of PARP-2 and GSK-3beta. In conclusion, PARP-2 is upregulated in the endometriotic tissue in response to estradiol (E2) and inhibition of it pharmacologically reduced the IHECs congregation and the endometriotic lesion, possibly affecting the inflammatory response via ILK-GSK-3beta, in the mouse model and human endometriotic cells.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151509"},"PeriodicalIF":2.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of age-related metabolomic signatures in vascular tissues

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-19 DOI: 10.1016/j.bbrc.2025.151513

Ya Zhao , Jingyue Zhang , Jiao Xia , Xiaoyan Han , Shuai Ben , Tianyi Liu , Wan Mu , Mudi Yao , Qin Jiang , Biao Yan

Vascular aging contributes to the morbidity and mortality in older individuals, closely linked to an imbalance between energy consumption and production. Despite its importance, our understanding of how aging affects vascular metabolism and leads to vascular diseases remains limited. In this study, we explored the metabolomic characteristics of vascular aging by analyzing aortic tissues from young and old mice through untargeted metabolomic analysis using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We identified 85 differential metabolites, with 37 up-regulated and 48 down-regulated, primarily consisting of lipids and lipid-like molecules, based on the criteria of variable importance in projection (VIP) > 1 and P < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant involvement of these metabolites in six metabolic pathways (P < 0.05), particularly in glycerophospholipid metabolism. Receiver operating characteristic (ROC) curve analysis highlighted eight altered metabolites in glycerophospholipid metabolism, such as phosphatidylcholine (PC) (17:0/22:6) and lysophosphatidylcholine (LPC) (18:2), which demonstrated strong discriminatory ability for vascular aging with an area under the curve (AUC) exceeding 0.85. This study provides novel insights into metabolomic signature of vascular aging, offering important clues for future treatments of age-related vascular disorders.

{"title":"Identification of age-related metabolomic signatures in vascular tissues","authors":"Ya Zhao , Jingyue Zhang , Jiao Xia , Xiaoyan Han , Shuai Ben , Tianyi Liu , Wan Mu , Mudi Yao , Qin Jiang , Biao Yan","doi":"10.1016/j.bbrc.2025.151513","DOIUrl":"10.1016/j.bbrc.2025.151513","url":null,"abstract":"<div><div>Vascular aging contributes to the morbidity and mortality in older individuals, closely linked to an imbalance between energy consumption and production. Despite its importance, our understanding of how aging affects vascular metabolism and leads to vascular diseases remains limited. In this study, we explored the metabolomic characteristics of vascular aging by analyzing aortic tissues from young and old mice through untargeted metabolomic analysis using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We identified 85 differential metabolites, with 37 up-regulated and 48 down-regulated, primarily consisting of lipids and lipid-like molecules, based on the criteria of variable importance in projection (VIP) > 1 and <em>P</em> < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant involvement of these metabolites in six metabolic pathways (<em>P</em> < 0.05), particularly in glycerophospholipid metabolism. Receiver operating characteristic (ROC) curve analysis highlighted eight altered metabolites in glycerophospholipid metabolism, such as phosphatidylcholine (PC) (17:0/22:6) and lysophosphatidylcholine (LPC) (18:2), which demonstrated strong discriminatory ability for vascular aging with an area under the curve (AUC) exceeding 0.85. This study provides novel insights into metabolomic signature of vascular aging, offering important clues for future treatments of age-related vascular disorders.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151513"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative analysis of transcriptomic profiles of mesenchymal stem cells at the onset of senescence and after exposure to acute exogenous oxidative stress

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-19 DOI: 10.1016/j.bbrc.2025.151506

Zozo Outskouni , Stavroula Prapa , Andreas Goutas , Eleftheria Klagkou , Giannis Vatsellas , Artemis Kosta , Varvara Trachana , Ioanna Papathanasiou

Cellular senescence can be triggered by a wide range of stress-inducing factors, including environmental and internal damaging events, such as oxidative stress. Moreover, stressed and senescent cells exhibit modifications in their transcriptional expression profile, but little is known regarding the common genes and pathways regulating these processes. Here, we analyzed the effects of long-term culture as well as exogenous acute oxidative stress on the transcriptional program of Wharton's jelly mesenchymal stem cells (WJ-MSCs). We demonstrate that, exposure to H₂O₂ compromised genomic stability and mitochondrial function in early passage WJ-MSCs, potentially initiating senescence to prevent cellular transformation. On the other hand, prolonged in vitro expansion of WJ-MSCs activated processes linked to integrins and extracellular matrix organization, possibly indicating the unfavorable consequences that senescence has on tissue integrity. Additionally, cells entering senescence and oxidative stressed young WJ-MSCs over-activated transcription factors related to permanent proliferative arrest and suppressed anti-senescence factors. Common differentially expressed genes in the late passage and H₂O₂-treated WJ-MSCs were implicated in DNA damage response and cell cycle arrest, which are known to trigger a senescent phenotype. Notably, the TP53INP1 gene emerged as a significantly upregulated gene in both late passage and H₂O₂-treated young WJ-MSCs, marking it as a potent senescence indicator. Silencing TP53INP1 mitigated the senescent phenotype, a role that appeared to be facilitated by autophagy regulation. Taken together, our results shed light on how transcriptomic changes govern MSCs' senescence program and identify key molecular drivers that could prove crucial for WJ-MSCs-based clinical applications.

{"title":"Comparative analysis of transcriptomic profiles of mesenchymal stem cells at the onset of senescence and after exposure to acute exogenous oxidative stress","authors":"Zozo Outskouni , Stavroula Prapa , Andreas Goutas , Eleftheria Klagkou , Giannis Vatsellas , Artemis Kosta , Varvara Trachana , Ioanna Papathanasiou","doi":"10.1016/j.bbrc.2025.151506","DOIUrl":"10.1016/j.bbrc.2025.151506","url":null,"abstract":"<div><div>Cellular senescence can be triggered by a wide range of stress-inducing factors, including environmental and internal damaging events, such as oxidative stress. Moreover, stressed and senescent cells exhibit modifications in their transcriptional expression profile, but little is known regarding the common genes and pathways regulating these processes. Here, we analyzed the effects of long-term culture as well as exogenous acute oxidative stress on the transcriptional program of Wharton's jelly mesenchymal stem cells (WJ-MSCs). We demonstrate that, exposure to H<sub>2</sub>O<sub>2</sub> compromised genomic stability and mitochondrial function in early passage WJ-MSCs, potentially initiating senescence to prevent cellular transformation. On the other hand, prolonged <em>in vitro</em> expansion of WJ-MSCs activated processes linked to integrins and extracellular matrix organization, possibly indicating the unfavorable consequences that senescence has on tissue integrity. Additionally, cells entering senescence and oxidative stressed young WJ-MSCs over-activated transcription factors related to permanent proliferative arrest and suppressed anti-senescence factors. Common differentially expressed genes in the late passage and H<sub>2</sub>O<sub>2</sub>-treated WJ-MSCs were implicated in DNA damage response and cell cycle arrest, which are known to trigger a senescent phenotype. Notably, the <em>TP53INP1</em> gene emerged as a significantly upregulated gene in both late passage and H<sub>2</sub>O<sub>2</sub>-treated young WJ-MSCs, marking it as a potent senescence indicator. Silencing <em>TP53INP1</em> mitigated the senescent phenotype, a role that appeared to be facilitated by autophagy regulation. Taken together, our results shed light on how transcriptomic changes govern MSCs' senescence program and identify key molecular drivers that could prove crucial for WJ-MSCs-based clinical applications.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"754 ","pages":"Article 151506"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0