Pub Date : 2025-07-01DOI: 10.1016/j.biocel.2025.106826
Ashira Manzoor, Khaled Barakat
TIM-3 (T cell immunoglobulin and mucin domain protein-3) is a potent checkpoint receptor that functions as a negative regulator of the immune response. Numerous immune cells, including monocytes, TH17 (T helper 17) cells, mast cells, myeloid cells, and Treg (regulatory T) cells, express TIM-3. It consists of four ligands: HMGB1 (High Mobility Group Protein B1), PtdSer (Phosphatidylserine), Galectin-9, and CEACAM-1 (Carcinoembryonic Antigen Cell Adhesion Molecule 1). Research has shown TIM-3's role in cancers, chronic viral infections, and autoimmune disorders. Inhibiting TIM-3, therefore, is a therapeutic approach in the current immunotherapy, particularly when combined with other immune checkpoint inhibitors. The review summarizes its function in different disorders and its potential signaling mechanisms.
{"title":"Therapeutic potential of TIM-3 inhibition in cancer, viral infections, and autoimmune disorders","authors":"Ashira Manzoor, Khaled Barakat","doi":"10.1016/j.biocel.2025.106826","DOIUrl":"10.1016/j.biocel.2025.106826","url":null,"abstract":"<div><div>TIM-3 (T cell immunoglobulin and mucin domain protein-3) is a potent checkpoint receptor that functions as a negative regulator of the immune response. Numerous immune cells, including monocytes, TH17 (T helper 17) cells, mast cells, myeloid cells, and Treg (regulatory T) cells, express TIM-3. It consists of four ligands: HMGB1 (High Mobility Group Protein B1), PtdSer (Phosphatidylserine), Galectin-9, and CEACAM-1 (Carcinoembryonic Antigen Cell Adhesion Molecule 1). Research has shown TIM-3's role in cancers, chronic viral infections, and autoimmune disorders. Inhibiting TIM-3, therefore, is a therapeutic approach in the current immunotherapy, particularly when combined with other immune checkpoint inhibitors. The review summarizes its function in different disorders and its potential signaling mechanisms.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106826"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561829","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}
Pub Date : 2025-06-26DOI: 10.1016/j.biocel.2025.106825
Zhuowei Shao , Jiankui Ye , Yili Wu , Yu Chen , Rong Wang , Shuai Fang , Shibo Wu
Background
Lung cancer is the primary reason for global cancer-related deaths. Targeted therapy is currently absent for lung squamous cell carcinoma (LUSC), a significant pathological subtype of lung cancer. The gene SPDYE3, a member of the Speedy/Ringo gene family, is highly expressed in different cancer tissues and functions as a cell cycle regulator. However, the potential mechanisms and clinical significance of SPDYE3 in LUSC remain unknown.
Method
Gene chip technology was used to detect the expression profiles of RNA in saliva, plasma, and normal controls of LUSC patients. Real-time quantitative polymerase chain reaction(qRT-PCR) was utilized to examine the expression and significance of SPDYE3 in the early diagnosis of LUSC. Furthermore, additional experiments were performed in vitro and in vivo to further assess the impact of SPDYE3 on the proliferation and cell cycle of LUSC. Further investigations were performed using IP, mass spectrometry analysis, and Western blotting to explore the interaction between SPDYE3 and cell division cycle 25 C (CDC25C).
Result
Our data showed that SPDYE3 is upregulated in LUSC tissues, plasma, and cells. SPDYE3 exhibited diagnostic usefulness, achieving an Area Under the Curve (AUC) of 0.7288. Experiments conducted in vitro and in vivo revealed that SPDYE3 enhances the growth and advancement of the cell cycle in LUSC cells. SPDYE3 mechanistically stimulates the activation of cyclin-dependent kinase 1 (CDK1) and controls the advancement of the cell cycle by interacting with CDC25C.
Conclusion
Overall, our results support the novel regulatory role of SPDYE3 in LUSC cell cycle progression mechanisms by influencing the CDC25C/CDK1 signaling pathway.
{"title":"SPDYE3 promotes cell cycle and LUSC progression by regulating the CDC25C/CDK1 pathway","authors":"Zhuowei Shao , Jiankui Ye , Yili Wu , Yu Chen , Rong Wang , Shuai Fang , Shibo Wu","doi":"10.1016/j.biocel.2025.106825","DOIUrl":"10.1016/j.biocel.2025.106825","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is the primary reason for global cancer-related deaths. Targeted therapy is currently absent for lung squamous cell carcinoma (LUSC), a significant pathological subtype of lung cancer. The gene SPDYE3, a member of the Speedy/Ringo gene family, is highly expressed in different cancer tissues and functions as a cell cycle regulator. However, the potential mechanisms and clinical significance of SPDYE3 in LUSC remain unknown.</div></div><div><h3>Method</h3><div>Gene chip technology was used to detect the expression profiles of RNA in saliva, plasma, and normal controls of LUSC patients. Real-time quantitative polymerase chain reaction(qRT-PCR) was utilized to examine the expression and significance of SPDYE3 in the early diagnosis of LUSC. Furthermore, additional experiments were performed in vitro and in vivo to further assess the impact of SPDYE3 on the proliferation and cell cycle of LUSC. Further investigations were performed using IP, mass spectrometry analysis, and Western blotting to explore the interaction between SPDYE3 and cell division cycle 25 C (CDC25C).</div></div><div><h3>Result</h3><div>Our data showed that SPDYE3 is upregulated in LUSC tissues, plasma, and cells. SPDYE3 exhibited diagnostic usefulness, achieving an Area Under the Curve (AUC) of 0.7288. Experiments conducted in vitro and in vivo revealed that SPDYE3 enhances the growth and advancement of the cell cycle in LUSC cells. SPDYE3 mechanistically stimulates the activation of cyclin-dependent kinase 1 (CDK1) and controls the advancement of the cell cycle by interacting with CDC25C.</div></div><div><h3>Conclusion</h3><div>Overall, our results support the novel regulatory role of SPDYE3 in LUSC cell cycle progression mechanisms by influencing the CDC25C/CDK1 signaling pathway.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106825"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517775","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}
Fibroblasts play a key role in maintaining skin structure and immune balance, but factors like aging, stress, and chronic inflammation can weaken their function, leading to collagen loss, thinning skin, and increased inflammation. Traditional collagen boosters like retinoic acid (RA), vitamin C (VC), hyaluronic acid (HA), and transforming growth factor beta (TGFβ) have drawbacks, including poor absorption, instability, and irritation.
Studies reveal that Silk Bioactive Peptide (27 P peptide) binds to epidermis and dermal fibroblasts, enhancing prolonged pro-collagen 1 (pro-C1) secretion in 3D and 2D models. De-novo collagen synthesis by 27 P peptide, likely regulated at the translational level, resulted in elevated collagen deposition and matrix remodeling up to 120 h. Combination of VC and 27 P peptide rescues VC-induced intracellular collagen depletion. Unlike TGFβ and RA, 27 P peptide maintains balance between fibroblast subpopulations, without inducing markers of fibrosis or inflammation. Together, 27 P peptide presents as a promising alternative to effectively promote collagen production, fibroblast homeostasis and skin health.
{"title":"27P silk bioactive peptides mediate multifaceted regulation of collagen and support balance in fibroblast subpopulations","authors":"SaiLavanyaa Sundar, Marios Frantzeskos Sardis, Lior Artzi, Aneesha Polisety, Setu Vora, Greg Altman, Svetlana Marukian","doi":"10.1016/j.biocel.2025.106821","DOIUrl":"10.1016/j.biocel.2025.106821","url":null,"abstract":"<div><div>Fibroblasts play a key role in maintaining skin structure and immune balance, but factors like aging, stress, and chronic inflammation can weaken their function, leading to collagen loss, thinning skin, and increased inflammation. Traditional collagen boosters like retinoic acid (RA), vitamin C (VC), hyaluronic acid (HA), and transforming growth factor beta (TGFβ) have drawbacks, including poor absorption, instability, and irritation.</div><div>Studies reveal that Silk Bioactive Peptide (27 P peptide) binds to epidermis and dermal fibroblasts, enhancing prolonged pro-collagen 1 (pro-C1) secretion in 3D and 2D models. <em>De-novo</em> collagen synthesis by 27 P peptide, likely regulated at the translational level, resulted in elevated collagen deposition and matrix remodeling up to 120 h. Combination of VC and 27 P peptide rescues VC-induced intracellular collagen depletion. Unlike TGFβ and RA, 27 P peptide maintains balance between fibroblast subpopulations, without inducing markers of fibrosis or inflammation. Together, 27 P peptide presents as a promising alternative to effectively promote collagen production, fibroblast homeostasis and skin health.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106821"},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340579","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}
Pub Date : 2025-06-19DOI: 10.1016/j.biocel.2025.106823
Jie Lu , Zhuo Lv , Meizhu xue , Dan Fan , Huiping Yang , Yi Hong , Yichen Wang , Zhangqiang Guo , Jiajun Ma , Jie Huang , Lijun Meng , Shuiyan Wu , Zhenjiang Bai
Plasmacytoid dendritic cells (pDCs) are crucial components of the immune response during viral infections, yet their function and development in the late phase of sepsis remain poorly understood. In this study, we investigated the impact of prolonged sepsis on pDCs and their progenitors in cecal ligation and puncture (CLP)-induced septic mice. We observed a significant reduction in both pDCs and their progenitors, alongside the presence of mature and regulatory pDCs. These mature and regulatory pDCs exhibited impaired type I interferon (IFN) secretion and antigen presentation capacity. In a Flt3L culture system of hematopoietic stem/progenitor cells (HSPCs) from CLP and Sham mice, we found that CLP-derived HSPCs exhibited an impaired ability to generate immunocompetent pDCs, as evidenced by lower IFN-α expression and reduced pDC recovery. Further investigation revealed downregulation of the key transcription factor TCF4 during pDC differentiation in these progenitor cells. Ectopic expression of TCF4 in these progenitors restored pDC generation. Additionally, we observed elevated levels of granulocyte colony-stimulating factor (G-CSF) in the bone marrow supernatant of septic mice. The addition of G-CSF to the culture system significantly impaired the generation of immunocompetent pDCs from HSPCs of normal mice. These findings suggest that sepsis may impair the production of immunocompetent pDCs from HSPCs by modulating key genes involved in pDC differentiation, potentially contributing to immune suppression and increased susceptibility to opportunistic infections in the later stages of sepsis.
{"title":"Sepsis impairs immunocompetent plasmacytoid dendritic cell reconstitution from hematopoietic stem/progenitor cell through altered bone marrow environment","authors":"Jie Lu , Zhuo Lv , Meizhu xue , Dan Fan , Huiping Yang , Yi Hong , Yichen Wang , Zhangqiang Guo , Jiajun Ma , Jie Huang , Lijun Meng , Shuiyan Wu , Zhenjiang Bai","doi":"10.1016/j.biocel.2025.106823","DOIUrl":"10.1016/j.biocel.2025.106823","url":null,"abstract":"<div><div>Plasmacytoid dendritic cells (pDCs) are crucial components of the immune response during viral infections, yet their function and development in the late phase of sepsis remain poorly understood. In this study, we investigated the impact of prolonged sepsis on pDCs and their progenitors in cecal ligation and puncture (CLP)-induced septic mice. We observed a significant reduction in both pDCs and their progenitors, alongside the presence of mature and regulatory pDCs. These mature and regulatory pDCs exhibited impaired type I interferon (IFN) secretion and antigen presentation capacity. In a Flt3L culture system of hematopoietic stem/progenitor cells (HSPCs) from CLP and Sham mice, we found that CLP-derived HSPCs exhibited an impaired ability to generate immunocompetent pDCs, as evidenced by lower IFN-α expression and reduced pDC recovery. Further investigation revealed downregulation of the key transcription factor TCF4 during pDC differentiation in these progenitor cells. Ectopic expression of TCF4 in these progenitors restored pDC generation. Additionally, we observed elevated levels of granulocyte colony-stimulating factor (G-CSF) in the bone marrow supernatant of septic mice. The addition of G-CSF to the culture system significantly impaired the generation of immunocompetent pDCs from HSPCs of normal mice. These findings suggest that sepsis may impair the production of immunocompetent pDCs from HSPCs by modulating key genes involved in pDC differentiation, potentially contributing to immune suppression and increased susceptibility to opportunistic infections in the later stages of sepsis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106823"},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340580","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}
Pub Date : 2025-06-15DOI: 10.1016/j.biocel.2025.106822
Yujin Dong, Wei Chang, Bei Lu, Yuanyuan Li, Yuanhua Liu
Ferroptosis could suppress the viability of cervical cancer cells and trigger their death, thereby offering a unique perspective for exploring novel therapeutic approach for cervical cancer. Here, this study tried to explore the role of N6-methyladenosine (m6A) methyltransferase methyltransferase-like 5 (METTL5) on cervical cancer ferroptosis. Elevated METTL5 functioned as an oncogene in cervical cancer tumorigenesis by inhibiting the ferroptosis. Mechanistically, METTL5 was verified to target SLC7A11 and installed the m6A methylation on SLC7A11 mRNA. Moreover, YTHDF3 bound with the m6A site of SLC7A11 mRNA to enhance SLC7A11 mRNA stability. Rescue assays confirmed that METTL5/YTHDF3/SLC7A11 axis inhibited the ferroptosis of cervical cancer cells. In vivo, METTL5 silencing repressed the tumor growth of cervical cancer cells, as well as reducing the SLC7A11. In conclusion, these data inspired that METTL5-mediated m6A modification of SLC7A11 promoted cervical cancer by inhibiting ferroptosis, providing a novel insight for cervical cancer.
{"title":"METTL5-mediated m6A modification of SLC7A11 promotes cervical cancer by inhibiting ferroptosis","authors":"Yujin Dong, Wei Chang, Bei Lu, Yuanyuan Li, Yuanhua Liu","doi":"10.1016/j.biocel.2025.106822","DOIUrl":"10.1016/j.biocel.2025.106822","url":null,"abstract":"<div><div>Ferroptosis could suppress the viability of cervical cancer cells and trigger their death, thereby offering a unique perspective for exploring novel therapeutic approach for cervical cancer. Here, this study tried to explore the role of N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) methyltransferase methyltransferase-like 5 (METTL5) on cervical cancer ferroptosis. Elevated METTL5 functioned as an oncogene in cervical cancer tumorigenesis by inhibiting the ferroptosis. Mechanistically, METTL5 was verified to target SLC7A11 and installed the m<sup>6</sup>A methylation on SLC7A11 mRNA. Moreover, YTHDF3 bound with the m<sup>6</sup>A site of SLC7A11 mRNA to enhance SLC7A11 mRNA stability. Rescue assays confirmed that METTL5/YTHDF3/SLC7A11 axis inhibited the ferroptosis of cervical cancer cells. In vivo, METTL5 silencing repressed the tumor growth of cervical cancer cells, as well as reducing the SLC7A11. In conclusion, these data inspired that METTL5-mediated m<sup>6</sup>A modification of SLC7A11 promoted cervical cancer by inhibiting ferroptosis, providing a novel insight for cervical cancer.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106822"},"PeriodicalIF":3.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318557","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}
Pub Date : 2025-06-11DOI: 10.1016/j.biocel.2025.106812
Henry A. Paz , Lasya Buddha , Tianfu Lam , Ying Zhong , James D. Sikes , Kartik Shankar , Aline Andres , Umesh D. Wankhade
Maternal weight and diet before and during pregnancy have a substantial impact on offspring metabolic health, though sex-specific differences in metabolic and adipose tissue adaptations to maternal overnutrition remain insufficiently understood. Using a mouse model of maternal high-fat (HF) diet-induced obesity, this study assessed the sexually dimorphic responses on offspring adiposity, physiology, and adipose tissue function. Male offspring of HF diet-fed dams exhibited greater weight gain and adiposity, impaired glucose homeostasis, elevated serum levels of insulin, leptin, and cholesterol, along with increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to female offspring. In established adipocyte cell lines independent of experimental animals, the expression of HSPs during differentiation was higher in white than in brown adipocytes. Also, expression of Hsp90ab1 in human umbilical cord mesenchymal stem cells tended to positively correlate with maternal body mass index in male, but not in female infants. This finding was generated independently of the animal model and were intended to strengthen the translational perspective of our work. Together, these results suggest a potential link between maternal diet, HSPs, and adipose tissue function.
{"title":"Maternal high-fat diet-induced obesity in offspring: Unraveling adipose tissue dysfunction mediated by increased heat shock proteins","authors":"Henry A. Paz , Lasya Buddha , Tianfu Lam , Ying Zhong , James D. Sikes , Kartik Shankar , Aline Andres , Umesh D. Wankhade","doi":"10.1016/j.biocel.2025.106812","DOIUrl":"10.1016/j.biocel.2025.106812","url":null,"abstract":"<div><div>Maternal weight and diet before and during pregnancy have a substantial impact on offspring metabolic health, though sex-specific differences in metabolic and adipose tissue adaptations to maternal overnutrition remain insufficiently understood. Using a mouse model of maternal high-fat (HF) diet-induced obesity, this study assessed the sexually dimorphic responses on offspring adiposity, physiology, and adipose tissue function. Male offspring of HF diet-fed dams exhibited greater weight gain and adiposity, impaired glucose homeostasis, elevated serum levels of insulin, leptin, and cholesterol, along with increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to female offspring. In established adipocyte cell lines independent of experimental animals, the expression of HSPs during differentiation was higher in white than in brown adipocytes. Also, expression of <em>Hsp90ab1</em> in human umbilical cord mesenchymal stem cells tended to positively correlate with maternal body mass index in male, but not in female infants. This finding was generated independently of the animal model and were intended to strengthen the translational perspective of our work. Together, these results suggest a potential link between maternal diet, HSPs, and adipose tissue function.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106812"},"PeriodicalIF":3.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280711","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}
Tunneling nanotubes (TNTs) are open membranous channels between connected cells, TNTs-mediated substance transfer between tumor cells plays an important role in drug resistance, metastasis and recurrence of tumors. This study aims to explore the composition of TNTs between tumor cells and the function of cofilin in TNTs formation. Oxidative stress induces the formation of TNTs between tumor cells. The components of TNTs include microfilaments and cell membranes, some of which contain microtubules, as well as mitochondria, endoplasmic reticulum, lysosomes, lipid droplets, ions, etc. Förster resonance energy transfer (FRET) analysis of living cells showed that cofilin and actin only interact in TNTs, and inhibition of cofilin can suppress oxidative stress-induced TNTs production. Doxorubicin (DOX) induced senescent tumor cells (STC) can form TNTs, and TNTs mediated material transfer between STC can promote tumor cell survival, while inhibition of cofilin can promote STC death. In summary, our data suggests that cofilin plays an important role in the formation of TNTs, and targeted inhibition of TNTs mediated intercellular communication and material exchange holds significant potential as a novel cancer treatment strategy.
{"title":"Cofilin is a key regulator of oxidative stress-induced intercellular tunneling nanotubes formation","authors":"Hongce Chen , Zhirui Wu , Lingyu Wang, Jingyao Zeng, Tongsheng Chen","doi":"10.1016/j.biocel.2025.106820","DOIUrl":"10.1016/j.biocel.2025.106820","url":null,"abstract":"<div><div>Tunneling nanotubes (TNTs) are open membranous channels between connected cells, TNTs-mediated substance transfer between tumor cells plays an important role in drug resistance, metastasis and recurrence of tumors. This study aims to explore the composition of TNTs between tumor cells and the function of cofilin in TNTs formation. Oxidative stress induces the formation of TNTs between tumor cells. The components of TNTs include microfilaments and cell membranes, some of which contain microtubules, as well as mitochondria, endoplasmic reticulum, lysosomes, lipid droplets, ions, etc. Förster resonance energy transfer (FRET) analysis of living cells showed that cofilin and actin only interact in TNTs, and inhibition of cofilin can suppress oxidative stress-induced TNTs production. Doxorubicin (DOX) induced senescent tumor cells (STC) can form TNTs, and TNTs mediated material transfer between STC can promote tumor cell survival, while inhibition of cofilin can promote STC death. In summary, our data suggests that cofilin plays an important role in the formation of TNTs, and targeted inhibition of TNTs mediated intercellular communication and material exchange holds significant potential as a novel cancer treatment strategy.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106820"},"PeriodicalIF":3.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263796","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}
Despite the great advances in medicine, there is a compelling need to develop alternative strategies to effectively treat obesity with the use of plant-origin therapeutics. Cannabigerol (CBG) appears to be a novel promising compound for managing this increasingly prevalent disease requiring multifaceted pharmacotherapy. Therefore, the herein study aimed to evaluate the potential therapeutic properties of 2-week CBG administration on the muscular metabolism of sphingolipids as well as insulin signal transduction pathway in a rat model of obesity and insulin resistance (IR) induced by high-fat, high-sucrose (HFHS) diet. The high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) were used to determine the sphingolipids content, while the multiplex assay kit was applied to measure the level of the phosphorylated form of proteins from the PI3K/Akt/mTOR pathway. The expression of various proteins engaged in the sphingolipid metabolism and insulin signaling was assessed using Western blotting. Our results showed that 2-week CBG treatment decreased the muscular content of most deleterious C16:0-Cer and C18:0-Cer ceramide species and reduced the intramuscular concentrations of sphinganine (SFA) and sphingosine (SFO), redirecting their metabolism toward phosphorylated derivatives, sphinganine-1-phosphate (SFA1P), and sphingosine-1-phosphate (S1P), respectively. Simultaneously, CBG counteracted S1P efflux in skeletal muscle, inhibiting the tissue-specific S1P/S1PR3 signaling. CBG also activated the PI3K/Akt/mTOR pathway, which increased the phosphorylation of protein kinase B (Akt) and its downstream targets in the myocytes of obese rats. These results suggest that CBG may play an essential homeostatic role in skeletal muscles and can protect from the development of obesity-associated metabolic derangements.
{"title":"Cannabigerol – A potent regulator of insulin sensitivity in rat’s skeletal muscle via targeting the sphingolipid metabolism and PI3K/Akt/mTOR pathway?","authors":"Patrycja Bielawiec , Lara Swierkot , Karolina Konstantynowicz-Nowicka , Adrian Chabowski , Agnieszka Błachnio-Zabielska , Ewa Harasim-Symbor","doi":"10.1016/j.biocel.2025.106819","DOIUrl":"10.1016/j.biocel.2025.106819","url":null,"abstract":"<div><div>Despite the great advances in medicine, there is a compelling need to develop alternative strategies to effectively treat obesity with the use of plant-origin therapeutics. Cannabigerol (CBG) appears to be a novel promising compound for managing this increasingly prevalent disease requiring multifaceted pharmacotherapy. Therefore, the herein study aimed to evaluate the potential therapeutic properties of 2-week CBG administration on the muscular metabolism of sphingolipids as well as insulin signal transduction pathway in a rat model of obesity and insulin resistance (IR) induced by high-fat, high-sucrose (HFHS) diet. The high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) were used to determine the sphingolipids content, while the multiplex assay kit was applied to measure the level of the phosphorylated form of proteins from the PI3K/Akt/mTOR pathway. The expression of various proteins engaged in the sphingolipid metabolism and insulin signaling was assessed using Western blotting. Our results showed that 2-week CBG treatment decreased the muscular content of most deleterious C16:0-Cer and C18:0-Cer ceramide species and reduced the intramuscular concentrations of sphinganine (SFA) and sphingosine (SFO), redirecting their metabolism toward phosphorylated derivatives, sphinganine-1-phosphate (SFA1P), and sphingosine-1-phosphate (S1P), respectively. Simultaneously, CBG counteracted S1P efflux in skeletal muscle, inhibiting the tissue-specific S1P/S1PR3 signaling. CBG also activated the PI3K/Akt/mTOR pathway, which increased the phosphorylation of protein kinase B (Akt) and its downstream targets in the myocytes of obese rats. These results suggest that CBG may play an essential homeostatic role in skeletal muscles and can protect from the development of obesity-associated metabolic derangements.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106819"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242819","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}
Nowadays, probiotic bacteria have been considered as a factor in the prevention and treatment of cancer, especially by induction of apoptosis. The aim of study, the isolation and identification of Bifidobacterium SPP, and to investigate the effects of bacterial cell extract and cell free supernatants (CFS) was on normal cell line and colon cancer cell line through measuring caspases.
Material and method
In this study, dairy products were collected and After isolation and identification of Bifidobacterium via PCR method, the cytotoxicity effects of cell free supernatants (CFS) (B.Bifidum S2 and B.Bifidum S3) and bacterial cell extract (B.Bifidum P6 and B.Bifidum P17) on colon cancer cell line (SW948) and normal cell line (HEK-293) were evaluated using MTT assay. The effect of isolated bacterial strains on apoptotic cells was determined by measuring caspases 1, 3, 9 and Bax by using ELISA kit.
Result
The results showed that the cytotoxicity effect of CFS was higher than bacterial cell extract. CFS showed the highest cytotoxicity effect (about 95 %) on colon cancer cell line. Quantitative analysis of Caspase-1, −3, 9, and Bax expression demonstrated that CFS may exert anticancer effects through induced apoptosis.
Conclusion
The results of the present research indicate that probably B.Bifidum S2 and B.Bifidum S3 isolates may be prevent colon cancer by inducing apoptosis.
{"title":"Bifidobacterium apoptosis induction by measuring bax and caspases on SW948 human colon cancer cell line","authors":"Maryam Soraya , Elham Moazamian , Seyedeh Azra Shamsdin , Mehdi Dehghani","doi":"10.1016/j.biocel.2025.106813","DOIUrl":"10.1016/j.biocel.2025.106813","url":null,"abstract":"<div><h3>Background</h3><div>Nowadays, probiotic bacteria have been considered as a factor in the prevention and treatment of cancer, especially by induction of apoptosis. The aim of study, the isolation and identification of <em>Bifidobacterium</em> SPP, and to investigate the effects of bacterial cell extract and cell free supernatants (CFS) was on normal cell line and colon cancer cell line through measuring caspases.</div></div><div><h3>Material and method</h3><div>In this study, dairy products were collected and After isolation and identification of <em>Bifidobacterium</em> via PCR method, the cytotoxicity effects of cell free supernatants (CFS) (<em>B.Bifidum</em> S2 and <em>B.Bifidum</em> S3) and bacterial cell extract (<em>B.Bifidum</em> P6 and <em>B.Bifidum</em> P17) on colon cancer cell line (SW948) and normal cell line (HEK-293) were evaluated using MTT assay. The effect of isolated bacterial strains on apoptotic cells was determined by measuring caspases 1, 3, 9 and Bax by using ELISA kit.</div></div><div><h3>Result</h3><div>The results showed that the cytotoxicity effect of CFS was higher than bacterial cell extract. CFS showed the highest cytotoxicity effect (about 95 %) on colon cancer cell line. Quantitative analysis of Caspase-1, −3, 9, and Bax expression demonstrated that CFS may exert anticancer effects through induced apoptosis.</div></div><div><h3>Conclusion</h3><div>The results of the present research indicate that probably <em>B.Bifidum</em> S2 and <em>B.Bifidum</em> S3 isolates may be prevent colon cancer by inducing apoptosis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"186 ","pages":"Article 106813"},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235797","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}
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