Diseases & research最新文献

{"title":"Krüppel-like Factor 2 (KLF2) Regulates Autophagy, Mitophagy, Mitochondrial Health, and Function During Foam Cell Formation.","authors":"Md Sariful Islam Howlader, Manjusri Das, Surajit Hansda, Prathyusha Naidu, Hiranmoy Das","doi":"10.54457/dr.202601003","DOIUrl":"10.54457/dr.202601003","url":null,"abstract":"<p><strong>Backgrounds: </strong>Foam cell (FC) formation is a hallmark of early atherosclerosis, driven by dysregulated lipid uptake, impaired mitochondrial clearance, and metabolic reprogramming in myeloid cells. However, the precise role of KLF2 in modulating autophagy, mitophagy, and glycolysis during FC formation remains inadequately explored.</p><p><strong>Methods: </strong>This study uncovers the critical regulatory role of Krüppel-like factor 2 (KLF2) during foam cell formation of myeloid cells (RAW264.7) using quantitative real-time PCR, immunocytochemistry, confocal microscopy, and glycolysis stress test methods.</p><p><strong>Results: </strong>Exposure to oxidized low-density lipoprotein (ox-LDL) suppressed autophagy and mitophagy markers in myeloid cells. It also increased glycolytic activity in myeloid cells during FC formation. A well-known chemical suppressor of KLF2, GGPP, further amplified these changes, highlighting the importance of endogenous KLF2 in maintaining mitochondrial health and metabolic functions during formation. To confirm the role of KLF2 in this process, when a chemical inducer of KLF2, GGTI298, was added during FC formation, it restored autophagic and mitophagic machinery, including the expression of Beclin1, LC3B, Parkin, and Pink1, and reversed the abnormal increase in glycolysis during FC formation.</p><p><strong>Conclusion: </strong>These findings demonstrate that KLF2 is a key transcriptional regulator that limits FC formation by preserving mitochondrial health and reducing excessive glycolysis. Furthermore, these results suggest KLF2 could be a target for future development of therapeutics for preventing FC formation, which is an early event in atherosclerosis development.</p>","PeriodicalId":519961,"journal":{"name":"Diseases & research","volume":"6 2","pages":"53-64"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KLF2 Promotes Ellagic Acid-Mediated Osteogenic Differentiation of Dental Pulp-Derived Stem Cells via Autophagy and Mitochondrial Regulation.","authors":"Prathyusha Naidu, Md Sariful Islam Howlader, Surajit Hansda, Manjusri Das, Hiranmoy Das","doi":"10.54457/dr.202504006","DOIUrl":"10.54457/dr.202504006","url":null,"abstract":"<p><strong>Backgrounds: </strong>Krüppel-like factor 2 (KLF2), a zinc-finger transcription factor of the Kruppel-like factor family, plays a crucial role in regulating various cellular processes, including differentiation, autophagy, and metabolism. However, it is not clear whether it has any role in the ellagic acid (EA)-mediated osteoblastic differentiation of dental pulp-derived stem cells (DPSCs). To investigate any regulatory role of KLF2 during EA-induced osteoblastic differentiation of DPSC, we have evaluated the path-ways emphasizing autophagy, mitophagy, and mitochondrial bioenergetics.</p><p><strong>Methods: </strong>We used induction and reduction of KLF2 approaches using chemical compounds, such as geranylgeranyl transferase inhibitor 298 (GGTI298), a known inducer of KLF2, and geranylgeranyl pyrophosphate (GGPP), a known inhibitor of KLF2. The key osteogenic, autophagy, and mitophagy markers were assessed via RT-qPCR and Western blotting, intracellular and mitochondrial ROS, along with mitochondrial membrane potential using high-resolution confocal microscopy, and cellular bioenergetics using Seahorse XF methods.</p><p><strong>Results: </strong>We found that EA alone significantly upregulated osteogenic markers, along with enhanced expression of autophagy and mitophagy-related molecules, and mitochondrial biogenetics. However, when we induced the KLF2, it amplified the expression of these markers and improved mitochondrial bioenergetics, suggesting a distinct relation between EA and KLF2. On the other hand, inhibition of KLF2 led to a significant downregulation of these markers.</p><p><strong>Conclusion: </strong>This supports the notion that KLF2 is a pivotal transcriptional regulator involved in mediating the pro-osteogenic effects of EA. It's activation enhanced autophagy, and improved mitochondrial bioenergetics, thereby facilitating EA-induced osteogenic differentiation of DPSCs. These findings refine our understanding of molecular mechanisms underlying polyphenol-mediated osteogenesis and show the pivotal role of KLF2 for regeneration via osteogenic differentiation of DPSCs.</p>","PeriodicalId":519961,"journal":{"name":"Diseases & research","volume":"6 1","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer.","authors":"Laxita Swain, Biswajit Das, Natalia Baran","doi":"10.54457/dr.202402015","DOIUrl":"10.54457/dr.202402015","url":null,"abstract":"<p><p>Breast cancer is a leading cause of death among women worldwide due to its aggressive nature, early metastasis, and resistance to standard chemotherapy. Doxorubicin (DOX) is a potent anticancer drug and remains one of the most effective treatments for breast cancer. This review delves into the diverse anticancer attributes of DOX, encompassing its ability to induce DNA damage, provoke the production of reactive oxygen species, facilitate various mechanisms of cell death, and promote or enhance an anti-tumor immune response. Through an analysis of both monotherapy and combination therapy approaches, this review underscores the immense significance of DOX in contemporary breast cancer treatment. It also delves into the limitations of DOX-based therapies and provides insights into future perspectives for research and development in this field.</p>","PeriodicalId":519961,"journal":{"name":"Diseases & research","volume":"5 1","pages":"19-36"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Effects of Arsenic Compounds in Non-Small Cell Lung Cancer.","authors":"Neelima Konduri, Anita Thyagarajan, Ravi P Sahu","doi":"10.54457/dr.202402003","DOIUrl":"10.54457/dr.202402003","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is the most common and prevalent subtype of lung cancer and continues to be one of the leading causes of cancer-related deaths worldwide. Despite various treatment options, a majority of NSCLC patients continue to experience disease progression and associated side effects, which are largely attributed to drug resistance, indicating the need for alternative strategies to combat this deadly disease. Among various applicable alternative approaches, repurposed drugs such as arsenic compounds have been shown to exert anticarcinogenic properties against NSCLC and possess the ability to overcome drug resistance mechanisms. Notably, numerous studies have demonstrated that the antitumor effects of arsenic compounds such as arsenic trioxide, arsenic sulfide, and tetra arsenic hexoxide are mediated via their ability to target several oncogenic signaling pathways, including nuclear factor-kappa B (NF-kB), epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3). Inhibition of such signaling cascades results in altered cellular activities, including cell cycle arrest, decreased proliferation, and increased apoptosis. Importantly, these arsenic compounds have also been shown to overcome tumor resistance mechanisms and/or exert synergy in combination with other therapeutic agents resulting in the augmentation of cancer cell cytotoxicity. This review highlights the anticarcinogenic mechanisms of arsenic compounds and their impact on the efficacy of therapeutic agents.</p>","PeriodicalId":519961,"journal":{"name":"Diseases & research","volume":"4 2","pages":"87-96"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferons in Colorectal Cancer Pathogenesis and Therapy.","authors":"Lucy Petrova, Fred Bunz","doi":"10.54457/dr.202401005","DOIUrl":"10.54457/dr.202401005","url":null,"abstract":"<p><p>As key modulators of the immune response, interferons play critical roles following infection and during the pathogenesis of cancer. The idea that these cytokines might be developed as new therapies emerged soon after their discovery. While enthusiasm for this approach to cancer therapy has waxed and waned over the ensuing decades, recent advances in cancer immunotherapy and our improved understanding of the tumor immune environment have led to a resurgence of interest in this unique class of biologic drug. Here, we review how interferons influence the growth of colorectal cancers (CRCs) and highlight new insights into how interferons and drugs that modulate interferon expression might be most effectively deployed in the clinic.</p>","PeriodicalId":519961,"journal":{"name":"Diseases & research","volume":"4 1","pages":"31-39"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAMTS Proteases: Their Multifaceted Role in the Regulation of Cancer Metastasis.","authors":"Rachele Bacchetti, Shengnan Yuan, Elena Rainero","doi":"10.54457/DR.202401004","DOIUrl":"10.54457/DR.202401004","url":null,"abstract":"<p><p>Cancer leads to nearly 10 million deaths worldwide per year. The tumour microenvironment (TME) is fundamental for tumour growth and progression. A key component of the TME, the extracellular matrix (ECM) has recently become a focus of interest in cancer research. Dysregulation of ECM synthesis and proteolysis leads to uncontrolled tumour growth and metastasis. Matrix remodelling enzymes, secreted by cancer cells and stromal cells, modify the overall structure and organisation of ECM proteins, therefore influencing biochemical interactions, tissue integrity and tissue turnover. While A Disintegrin and Metalloproteinases (ADAMs)' and matrix metalloproteinases' role in cancer has been deeply investigated, other proteolytic enzymes, like ADAMs with thrombospondin(-like) motifs (ADAMTSs) have been gaining interest due to their roles in modulating cancer cell-ECM interactions and oncogenic signalling pathways. In this review, we will discuss the dysregulation of ADAMTSs in cancer and their roles in regulating cancer development and progression, via ECM remodelling and cell signalling modulation.</p>","PeriodicalId":519961,"journal":{"name":"Diseases & research","volume":"4 1","pages":"40-52"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}