Exploration of medicine最新文献

{"title":"The future of cervical cancer prevention: advances in research and technology","authors":"Praveen Kumar Chandra Sekar, Sheena Mariam Thomas, Ramakrishnan Veerabathiran","doi":"10.37349/emed.2024.00226","DOIUrl":"https://doi.org/10.37349/emed.2024.00226","url":null,"abstract":"This article provides an informative overview of the current situation and future trends in cervical cancer prevention. Cervical cancer remains a significant public health concern worldwide and is characterized by notable variations in both incidence and mortality rates between developed and developing countries. This underscores the importance of understanding the pathophysiology of cervical cancer, stressing the involvement of high-risk HPV types. The presence of supplementary risk factors facilitates the transition from infection to cancer. This review examines current preventive methods, including the success of HPV vaccines such as Gardasil and Cervarix, and the effectiveness of screening techniques, from cytology to HPV DNA testing. It noted the limitations faced by primary and secondary preventive measures, particularly in low-resource settings, which include access to vaccines and effective screening procedures. Emerging technologies in cervical cancer prevention, such as liquid-based cytology, molecular testing, and AI, promise to improve early detection and diagnosis accuracy and efficiency. The potential of precision medicine to customize treatment based on individual risk factors was discussed. It explores the innovation in genetic editing techniques, such as CRISPR/Cas9, in targeting HPV oncoproteins, the advent of immunotherapy, the role of tumor-infiltrating lymphocytes, and the prospects of biomarkers in improving early detection. Research and technological advancements are leading to transformative changes in cervical cancer prevention. These developments suggest a path toward improved screening, diagnosis, and treatment that could significantly reduce the global burden of the disease. However, realizing the full potential of these advances requires inclusive research and international collaboration to overcome access disparities, particularly in resource-limited settings.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141111410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of vitamin D on ultraviolet-induced photoaging and skin diseases","authors":"Sankalya S. Ambagaspitiya, Gayan A. Appuhamillage, R. Dassanayake","doi":"10.37349/emed.2024.00225","DOIUrl":"https://doi.org/10.37349/emed.2024.00225","url":null,"abstract":"Excessive exposure to ultraviolet (UV) radiation causes premature aging of the skin, known as photoaging. UV radiation induces DNA damage, oxidative stress, inflammatory reactions, and degradation of extracellular matrix (ECM) proteins, contributing to the aged skin phenotype. The skin synthesizes vitamin D upon UVB exposure, which plays a pivotal role in the proper function of multiple body systems. Vitamin D protects skin from photo-damage by repairing cyclobutane pyrimidine dimers, reversing oxidative stress, and reducing chronic inflammation. Moreover, various epidemiological studies have identified vitamin D deficiency as a marker for common dermatological disorders. Improvement of clinical outcomes with vitamin D supplementation further suggests its protective role against skin pathologies. This review comprehensively covers the involvement of vitamin D in combating UV-induced photoaging and various skin disorders, highlighting the significance of maintaining vitamin D adequacy for healthy skin.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141121778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologically driven nanodrug delivery system for targeted lung cancer treatment","authors":"Shiying Zhang, Xia Li, Yang Liu, Hui Li, Zhiyue Zhang","doi":"10.37349/emed.2024.00221","DOIUrl":"https://doi.org/10.37349/emed.2024.00221","url":null,"abstract":"Lung cancer remains a leading cause of cancer-related deaths globally, and a significant number of patients are ineligible for surgery, while chemoradiotherapy often shows limited efficacy, a systemic distribution, a low drug concentration at tumor sites, severe side effects, and the emergence of drug resistance. In this context, a nanodrug delivery system (NDDS) has emerged as a promising approach for lung cancer treatment, offering distinct advantages such as targeted delivery, responsiveness to the tumor microenvironment, site-specific release, and enhanced induction of apoptosis in cancer cells, ultimately leading to tumor growth inhibition or even elimination. This review aims to provide an overview of the physiological characteristics of lung cancer, highlight the limitations of conventional treatment methods, and extensively examine recent significant advancements in NDDS utilized for lung cancer therapy. The findings from this review lay the foundation for further development and optimization of NDDSs in the treatment of lung cancer.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of alimentary-derived bacterial metabolites on energy metabolism in colonic epithelial cells and inflammatory bowel diseases","authors":"M. Andriamihaja, François Blachier","doi":"10.37349/emed.2024.00220","DOIUrl":"https://doi.org/10.37349/emed.2024.00220","url":null,"abstract":"In this review, we present the main luminal fuels that are responsible for energy production in colonocytes, namely the bacterial metabolites short-chain fatty acids and lactate, which are produced from undigestible polysaccharides and proteins, and hydrogen sulfide that is mainly produced from undigested proteins. In addition to these luminal fuels, colonocytes can use glutamine, and to a lower extent glucose, as energy substrates provided by arterial capillaries. The effects of excessive concentrations of bacterial metabolites within the colonic luminal fluid (including butyrate, hydrogen sulfide, p-cresol, indole derivatives, ammonia, 4-hydroxyphenylacetic acid, and acetaldehyde) on the mitochondrial energy metabolism in colonic epithelial cells and the consequences of altered ATP production on the colonic epithelium renewal and barrier function are detailed, as well as consequences for water and electrolyte absorption. The relationships between modifications of these latter processes and development of colitis are then discussed. Finally, several mechanisms that are considered as adaptive against deleterious effects of bacterial metabolites on colonic epithelial cell energy metabolism are presented.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicinal and immunological aspects of bacteriophage therapy to combat antibiotic resistance","authors":"Isra Noor, Muhammad Hassan Nasir, Aneeq Ur Rehman, Noof Javed, Warda Waheed, Areeba Waheed, Ishmal Jamil, Wajeeha Shafiq, Muhammad Haseeb, Divya Dhawal Bhandari, Hitesh Chopra, A. Othman","doi":"10.37349/emed.2024.00217","DOIUrl":"https://doi.org/10.37349/emed.2024.00217","url":null,"abstract":"Bacteriophages are viruses that infect bacterial cells and use their machinery to reproduce. This unique characteristic holds immense promise for combating antibiotic-resistant bacterial infections, a growing global threat. There are two types: one of them is named temperate phages, which inject their genomic material into bacteria and integrate into the host’s genome, while the second one is entitled as lytic phages that subdue the entire metabolism of the bacterium for the synthesis of its genome and proteins, including lytic proteins involved in breaking bacterial cell membrane and release of novel phages. In addition, phage therapy can be expressed through anti-biofilm activity and by triggering innate and adaptive immune cells responses. Moreover, no adverse effects of phage therapy have been reported. However, phage therapy is still grim for many and could influence some interpretations related to immune response, bacteriophage selections, and phage resistance in the future.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140673863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between gingival and peri-implant sulcular fluid active matrix metalloproteinase-8 concentration and clinical indices in healthy and diseased conditions","authors":"R. Guarnieri, Rodolfo Reda, Alessio Zanza, E. Xhajanka, Shankargouda Patil, D. Di Nardo, L. Testarelli","doi":"10.37349/emed.2024.00219","DOIUrl":"https://doi.org/10.37349/emed.2024.00219","url":null,"abstract":"Aim: The study was to evaluate the active matrix metalloproteinase-8 (aMMP-8) concentration in gingival crevicular fluid (GCF) and in peri-implant sulcular fluid (PISF) in healthy and diseased conditions, before and after non-surgical treatment, and to compare it with the various clinical parameters used to estimate the gingival and peri-implant inflammation. Methods: Plaque index/modified PI (PI/mPI), gingival index/simplified GI (GI/sGI), probing depth (PD), bleeding on probing index/modified BOPI (BOPI/mBOPI), radiographic bone loss/radiographic marginal bone loss (rBL/rMBL), and GCF/PISF samples were evaluated, before and 3 months after non-surgical treatment, GCF/PISF samples were analyzed by a chair-side mouth-rinse test (ImplantSafe®) in combination with a digital reader (ORALyzer®). Results: In all groups, aMMP-8 median levels were statistically higher in the PISF than in GCF and they did not change after treatment. Moreover, it was statistically higher in Group 3 (periodontitis/peri-implantitis) compared to the other groups. A positive correlation of the GCF/PISF and aMMP-8 median concentration was seen with increasing PD and BOPI/mBOPI values. A higher covariation of aMMP-8 mean levels in GCF with PD was found when compared to PISF levels. aMMP-8 mean levels in PISF expressed a higher covariation with increasing grades of sGI, rMBL, and BOPI while aMMP-8 GCF concentration established a better covariation with PD and PI. Conclusions: PISF of sites with peri-implant mucositis and peri-implantitis showed higher levels of aMMP-8 compared to sites with gingivitis and periodontitis. Compared to clinical indices, aMMP-8 concentration in GCF/PISF can be a beneficial adjunctive diagnostic tool for early identification and screening of the risk of peri-implant diseases. After non-surgical therapy, PISF aMMP-8 concentration remained mostly unchanged, while the GCF concentration of aMMP-8 significantly decreased.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular adenylate energy charge and adenine nucleotides in brain tissue during hypoglycemia in newly born BALB/c mice pups","authors":"Hassib Narchi, Priyadharshini Yuvaraju, Junu A. George, Richard L. Jayaraj, Radhakrishnan Subramanian","doi":"10.37349/emed.2024.00218","DOIUrl":"https://doi.org/10.37349/emed.2024.00218","url":null,"abstract":"Aim: Hypoglycemia occurs in the neonatal period but the exact pathophysiology of the resulting brain injury at the cellular level is not well known. Therefore, a neonatal murine model was developed with insulin-induced hypoglycemia, to analyze the in-vitro effects of hypoglycemia on brain nucleotides and adenylate energy charge (AEC) throughout the first ten days of life. Methods: Newly born BALB/c pups between one and ten days of age were used. In each age group, six pups were subjected to insulin-induced hypoglycemia and six others served as controls. In both groups, immediately after euthanasia, brain tissues were collected. The in-vitro effects of hypoglycemia on brain nucleotides [adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP)] were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) as well on AEC. Results: In the controls, the cellular AEC steadily decreased with age by at least 50% over the 10-day study period (P < 0.05) except in the parietal tissue (P = 0.30) where it remained stable throughout that period. The most marked decrease was observed in the occipital tissue (P < 0.001). In the hypoglycemic mice, AEC in both the parietal and occipital tissues decreased significantly more than in the controls, more rapidly and pronounced between day 2 and 5 in the occipital tissue, reaching very low levels from day 5 onward. Except in the occipital tissue, none of the adenine nucleotides on its own, including ATP, reflected the cellular AEC. Conclusions: Over the first ten days of life, hypoglycemia progressively depleted cellular AEC in the brain, unlike cellular ATP concentration which did not appropriately reflect cellular energy.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140676732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between circulating CD34+CD133+ endothelial progenitor cells and reduced risk of Alzheimer’s disease in the Framingham Heart Study","authors":"Yixuan Wang, Jinghan Huang, T. F. Ang, Yibo Zhu, Q. Tao, Jesse B. Mez, M. Alosco, Gerald V. Denis, A. Belkina, A. Gurnani, Mark Ross, Bin Gong, Jingyan Han, Kathryn L. Lunetta, T. Stein, Rhoda Au, Lindsay A. Farrer, Xiaoling Zhang, Wei Qiao Qiu","doi":"10.37349/emed.2024.00216","DOIUrl":"https://doi.org/10.37349/emed.2024.00216","url":null,"abstract":"Aim: Endothelial dysfunction has been associated with both cerebrovascular pathology and Alzheimer’s disease (AD). However, the connection between circulating endothelial cells and the risk of AD remains uncertain. The objective was to leverage data from the Framingham Heart Study to investigate various circulating endothelial subtypes and their potential correlations with the risk of AD. Methods: The study conducted data analyses using Cox proportional hazard regression and linear regression methods. Additionally, genome-wide association study (GWAS) was carried out to further explore the data. Results: Among the eleven distinct circulating endothelial subtypes, only circulating endothelial progenitor cells (EPCs) expressing CD34+CD133+ were found to be negatively and dose-dependently associated with reduced AD risk. This association persisted even after adjusting for age, sex, years of education, apolipoprotein E (APOE) ε4 status, and various vascular diseases. Particularly noteworthy was the significant association observed in individuals with hypertension and cerebral microbleeds. Consistently, positive associations were identified between CD34+CD133+ EPCs and specific brain regions, such as higher proportions of circulating CD34+CD133+ cells correlating with increased volumes of white matter and the hippocampus. Additionally, a GWAS study unveiled that CD34+CD133+ cells influenced AD risk specifically in individuals with homozygous genotypes for variants in two stem cell-related genes: kirre like nephrin family adhesion molecule 3 (KIRREL3, rs580382 CC and rs4144611 TT) and exocyst complex component 6B (EXOC6B, rs61619102 CC). Conclusions: The findings suggest that circulating CD34+CD133+ EPCs possess a protective effect and may offer a new therapeutic avenue for AD, especially in individuals with vascular pathology and those carrying specific genotypes of KIRREL3 and EXOC6B genes.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The low expression of matrix metalloproteinases: a key to longevity?","authors":"K. Sak","doi":"10.37349/emed.2024.00213","DOIUrl":"https://doi.org/10.37349/emed.2024.00213","url":null,"abstract":"Over the past few decades, it has become clear that an excessive activity of matrix metalloproteinases (MMPs) can accelerate the progression and fatal outcomes of several serious age-related diseases, including atherosclerotic coronary heart disorders and various types of malignancies. These proteolytic enzymes mediate the degradation and remodeling of the extracellular matrix through cleaving its various components, thereby affecting many critical functions of surrounding cells and intercellular communication. Consequently, the low expression levels of MMPs can be important in the prevention and treatment of such chronic life-threatening pathologies, contributing to the better quality of life and longer life expectancy. In this review article, the pathogenic proteolytic roles of MMPs are examined in more detail, especially in the cases of heart attack and stroke as well as cancer invasion and metastasis, showing that these enzymes can be considered not only as diagnostic and prognostic biomarkers but also as important therapeutic targets in the fight against many age- and lifestyle-related serious disorders. The identification and development of suppressing agents with a selective activity towards specific MMPs have, however, still remained a complex and complicated challenge, in which natural plant-derived compounds are increasingly recognized as promising leads for the new-generation inhibitors.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140728975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol de novo biosynthesis: a promising target to overcome the resistance to aromatase inhibitors in postmenopausal patients with estrogen receptor-positive breast cancer","authors":"D. Coradini, Federico Ambrogi","doi":"10.37349/emed.2023.00196","DOIUrl":"https://doi.org/10.37349/emed.2023.00196","url":null,"abstract":"Aim: Cholesterol is an essential component of cell membranes and serves as a precursor for several bioactive molecules, including steroid hormones and isoprenoids. Generally supplied by the bloodstream, the de novo cholesterol biosynthesis is activated in response to an increased cell requirement due to normal tissue remodeling or tumor proliferation. In estrogen receptor (ER)-positive breast cancers, cholesterol biosynthesis may promote and sustain tumor growth and concur with the failure of the treatment with aromatase inhibitors. Methods: In this study, the comparison of gene compared the expression involved in cholesterol biosynthesis was conducted in ER-positive tumors that were responsive and nonresponsive to letrozole; besides, an exploration of their association with genes implicated in estrogen production, the Hippo pathway, and cell cycle control was performed. Results: In responsive tumors, letrozole significantly decreased the expression of five genes [acetyl-coenzyme A (CoA) acetyltransferase 2 (ACAT2), 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), farnesyl diphosphate synthase (FDPS), and squalene epoxidase (SQLE)] crucial for the biosynthetic process. Conversely, in nonresponsive tumors, these genes were unaffected by letrozole but associated with several genes involved in estrogens production [cytochrome P450 family 19 subfamily A member 1 (CYP19A1), hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2), and sulfotransferase family 1A member 1 (SULT1A1)], cell cycle [control cyclin dependent kinase 4 (CDK4) and CDK6], and Hippo pathway [Yes1 associated transcriptional regulator (YAP1) and baculoviral inhibitor of apoptosis (IAP) repeat containing 5 (BIRC5)]. Conclusions: The findings corroborated the notion that the dysregulation of the mevalonate pathway may contribute to the resistance to letrozole and supported the use of statins to contrast this metabolic dysfunction.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139143278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}