Current molecular pharmacology最新文献

{"title":"PCSK9 Biomarker and Key Modulator for Cardiovascular Disorders: Heralding a New Therapeutic Era and Their Future Perspectives.","authors":"Jitendra Gupta,&nbsp;Reena Gupta","doi":"10.2174/1874467216666221202144813","DOIUrl":"https://doi.org/10.2174/1874467216666221202144813","url":null,"abstract":"<p><p>Cardiovascular disorders (CVDs) are the leading cause of death worldwide and are accelerated via the low level of low-density lipoprotein-cholesterol (LDL-C). The proprotein convertase subtilis/kexin type9 (PCSK9), a vital regulator and a biomarker, circulates for the LDL-C and has the degradation capability of the low-density lipoprotein receptor (LDLR). PCSK9 has modulated the overall mechanism by transcription, secretion, clearance, or extracellular inactivation in the past few years.PCSK9 has specific pathophysiological roles in many cardiovascular cells. The initial data on the PCSK9 inhibitor, Evolocumab, has a specific reduction in the composite end-point, such as cardiovascular, myocardial, and stroke, while the rest of the data release is still under wait. Furthermore, it is witnessed that the U.S. and the European authorities have approved two humanized antibodies against the LDL-R binding site of PCSK9. This review highlighted the recent data findings on the PCSK9 and its regulation, focusing on cardiovascular disorders, and summarized the current clinical studies. Thus it provides a ray of hope to overcome statin intolerance and alternative approaches for PSCK9 inhibition and significantly reduce cardiovascular complications. This review plays a pivotal role for the researchers and scientists working on PCSK9 inhibitors to treat cardiovascular disorders.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 8","pages":"832-854"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guggulsterone Promotes Nasopharyngeal Carcinoma Cells Exosomal Circfip1L1 to Mediate miR-125a-5p/VEGFA Affecting Tumor Angiogenesis.","authors":"Ting Zhou,&nbsp;Shunli Zhao,&nbsp;Sanyuan Tang,&nbsp;Yongli Wang,&nbsp;Ruoxia Wu,&nbsp;Xiaoyan Zeng,&nbsp;Ping Yang,&nbsp;Xi Zhang,&nbsp;Xuefei Tian","doi":"10.2174/1874467216666230111112116","DOIUrl":"https://doi.org/10.2174/1874467216666230111112116","url":null,"abstract":"<p><strong>Background: </strong>Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone (GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1 from NPC cells and its regulatory mechanism.</p><p><strong>Methods: </strong>NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments. HNE1 cells were treated with GS (20, 40, 60 μmol/L). The expressions of miR-125a-5p and circFIP1L1 were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs.</p><p><strong>Results: </strong>miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a- 5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting the VEGFA pathway to repress HUVECs angiogenesis.</p><p><strong>Conclusions: </strong>GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis affecting tumor angiogenesis.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 8","pages":"870-880"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9565829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of Altered Oncogenic and Tumor Suppressor microRNA Expression in Breast Cancer and Colorectal Cancer Cell using Epicatechin.","authors":"Sheetal Kiran,&nbsp;Abhilipsa Patra,&nbsp;Poonam Verma,&nbsp;Suvendu Purkait,&nbsp;Gaurav Chhabra,&nbsp;Praveen Kumar Guttula,&nbsp;Amit Ghosh","doi":"10.2174/1874467216666230210091839","DOIUrl":"10.2174/1874467216666230210091839","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNA) are small non-coding RNAs that regulate the function of mRNA post-transcriptionally in a tissue-specific manner. miRNA expressions are heavily dysregulated in human cancer cells through various mechanisms, including epigenetic changes, karyotype abnormalities, and miRNA biogenesis defects. miRNAs may act as either oncogenes or tumor suppressors under different conditions. Epicatechin is a natural compound found in green tea which possesses antioxidant and antitumor properties.</p><p><strong>Objective: </strong>The objective of this study is to investigate the effect of epicatechin treatment on the expression level of several oncogenic and tumor suppressor miRNAs in breast and colorectal cancer cell lines (MCF7 and HT-29) and identify its mechanism of action.</p><p><strong>Methods: </strong>The MCF-7 and HT29 cells were treated with epicatechin for 24 hours and untreated cells were considered control cultures. miRNA was isolated and qRT-PCR was used to measure the expression profile changes of different oncogenic and tumor suppressor miRNAs. Furthermore, the mRNA expression profile was also screened at different concentrations of epicatechin.</p><p><strong>Results: </strong>Our results showed several-fold changes in miRNAs expression level, which is cell line specific. Also, epicatechin at different concentrations induces biphasic changes in mRNA expression levels in both cell lines.</p><p><strong>Conclusion: </strong>Our findings first time demonstrated that epicatechin can reverse the expression of these miRNAs and may trigger the cytostatic effect at a lower concentration.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 8","pages":"915-926"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scutellarin Mediates Cytochrome P450 3A4 and 2C19 Expression via Pregnane X Receptor and Constitutive Androstane Receptor.","authors":"Hangxing Huang,&nbsp;Change Cao,&nbsp;Zhimin Miao,&nbsp;Xiaoli Yang,&nbsp;Yong Lai","doi":"10.2174/1874467215666220823123852","DOIUrl":"https://doi.org/10.2174/1874467215666220823123852","url":null,"abstract":"<p><strong>Background: </strong>Breviscapine is a flavonoid extracted from Erigeron breviscapus (Vant.) Hand.-Mazz., and mainly contains scutellarin. Nuclear receptors play important roles in regulating transporter and drug metabolic enzymes.</p><p><strong>Objective: </strong>To investigate the regulatory effects of scutellarin on CYP3A4 and 2C19 in HepG2 and Caco-2 cells based on nuclear receptors PXR and CAR.</p><p><strong>Methods: </strong>The proteins and mRNA levels of CYP3A4 and CYP2C19 treated with scutellarin were detected by Western Blot and RT-qPCR. Using assays of the dual-luciferase reporter, promoter sequences containing hPXR and hCAR protein recognition and binding regulatory elements CYP3A4 and CYP2C19 were inserted upstream of the reporter gene, and the expression vector and the reporter vector were cotransfected into HepG2 and Caco-2 cells.</p><p><strong>Results: </strong>Scutellarin inhibited mRNA of CYP3A4 and PXR, and promoted mRNA expression of CYP2C19 and CAR in RT-qPCR results. Western-blot results showed scutellarin inhibited the expression of CYP3A4 and promoted the expression of CYP2C19. The dual-luciferase reporter genes showed that scutellarin enhanced the expression level of CYP2C19, and when its concentration was 40 and 80μmol/L, CYP3A4 was significantly increased.</p><p><strong>Conclusion: </strong>Scutellarin down-regulates CYP3A4 through PXR, and its mechanism may work by up-regulating CAR, binding to PXR to inhibit PXR-mediated expression of CYP3A4. Scutellarin up-regulates CYP2C19 through CAR.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 6","pages":"640-653"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor Organoid Model and Its Pharmacological Applications in Tumorigenesis Prevention.","authors":"Yuwei Qiang,&nbsp;Ninghua Yao,&nbsp;Fan Zuo,&nbsp;Shi Qiu,&nbsp;Xiaolei Cao,&nbsp;Wenjie Zheng","doi":"10.2174/1874467215666220803125822","DOIUrl":"https://doi.org/10.2174/1874467215666220803125822","url":null,"abstract":"<p><p>Cancer is a leading cause of death and a severe threat to global public health. Organoid, as a novel 3D in vitro model, has been applied in various tumor related studies due to its apparent advantages. The organoid is mainly constructed by Matrigel-depended 3D culture system, Air-Liquid Interface (ALI) culture, and Microfluidic culture or Organ-on-chips platform. For the application in carcinogenesis studies, the organoid model may favor depicting initiative hallmarks and identifying potential intervening targets, investigating driver genes of carcinogenesis, and identifying known or unknown risk or protective factors. In this review, we discussed different organoid construction methods and their properties. We also noted that tumor organoids can portray initiative hallmarks and identify possible intervening targets, as well as explore carcinogenesis driver genes and uncover known or unknown risks or protective factors. Organoid systems have been used to identify tumor-preventive drugs such as oligomeric proanthocyanidins, Vitamin D, n-3 PUFAs, and pomegranate. The current evidence underscores the organoid model's potential importance in developing innovative tumorprevention techniques.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 4","pages":"435-447"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9650514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 and Diabetes: will Novel Drugs for Diabetes Help in COVID-19?","authors":"Hayder M Al-Kuraishy,&nbsp;Ali I Al-Gareeb,&nbsp;Gomaa Mostafa-Hedeab,&nbsp;Rupal Dubey,&nbsp;Pranav Kumar Prabhakar,&nbsp;Gaber El-Saber Batiha","doi":"10.2174/1874467215666220908091604","DOIUrl":"https://doi.org/10.2174/1874467215666220908091604","url":null,"abstract":"<p><p>COVID-19 is caused by the SARS-CoV-2 virus, which has afflicted more than 245.37 million individuals worldwide and resulted in more than 4.9 million deaths as of today, with a mortality rate of 2.1%. Diabetes mellitus (DM) and its secondary complications are the major serious global health concerns today due to its growth rate, and it is the fastest-growing non-communicable disease. According to International Diabetes Federation (IDF) data, one out of 11 adults is diabetic, and the projection says that the figure will reach 642 million by 2040 globally. The occurrence of DM and its secondary complications is also associated with the severity of COVID-19 and high mortality. People with DM have a weakened immune system owing to innate immunity defects affecting phagocytosis, neutrophil chemotaxis, and cellmediated immunity; however, the high prevalence of diabetes in serious cases of COVID-19 may reflect the higher prevalence of type 2 DM (T2DM) in older people. Moreover, DM is linked to cardiovascular illness in older people, which could underlie the correlation between COVID-19 and fatal outcomes. SARS-CoV-2 infects via the angiotensin-converting enzyme 2 (ACE2), which is found in pancreatic islets, and infection with SARS-CoV-1 has been linked to hyperglycemia in individuals who do not have DM. And hence diabetic patients need to take more precautions and maintain their blood glucose levels. Many pieces of research say that COVID-19 and DM, especially its secondary complications are interlinked. But it also needs more elaborative evidence on whether the anti-diabetic drugs can manage only blood glucose or SARS-CoV-2.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 4","pages":"494-506"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9676424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Modafinil (Provigil) on Memory and Learning in Experimental and Clinical Studies: From Molecular Mechanisms to Behaviour Molecular Mechanisms and Behavioural Effects.","authors":"Mohammad Yassin Zamanian,&nbsp;Mahdi Najafiani Karimvandi,&nbsp;Marjan Nikbakhtzadeh,&nbsp;Elham Zahedi,&nbsp;Dmitry Olegovich Bokov,&nbsp;Małgorzata Kujawska,&nbsp;Mahsa Heidari,&nbsp;Mohammad Reza Rahmani","doi":"10.2174/1874467215666220901122824","DOIUrl":"https://doi.org/10.2174/1874467215666220901122824","url":null,"abstract":"<p><p>Modafinil (MOD, 2-diphenyl-methyl-sulphinil-2-acetamide) is a stimulant-like medicine used to treat narcolepsy. Off-label uses include improving cognitive ability in the course of other diseases. This review aims to discuss findings demonstrating the memory and learningenhancing activity of MOD in experimental and clinical studies. We included behavioral evaluations alongside the effects of MOD at the cellular and molecular level. MOD in different animal disease models exerted beneficial effects on induced memory and learning impairment, which in some cases were accompanied by modulation of neurotransmitter pathways or neuroplastic capabilities, reducing oxidative stress, or expression of synaptic proteins. Individuals treated with MOD showed improved memory and learning skills in different conditions. These effects were associated with regulating brain activity in some participants, confirmed by functional magnetic resonance imaging. Presented herein, data support the use of MOD in treating memory and learning deficits in various disease conditions.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 4","pages":"507-516"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9307071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Signaling Pathway by Curcumin in Osteosarcoma.","authors":"Parnia Rahnamay Farnood,&nbsp;Romina Danesh Pazhooh,&nbsp;Zatollah Asemi,&nbsp;Bahman Yousefi","doi":"10.2174/1874467215666220408104341","DOIUrl":"https://doi.org/10.2174/1874467215666220408104341","url":null,"abstract":"<p><p>The most prevalent primary bone malignancy among children and adolescents is osteosarcoma. The high mortality rate of osteosarcoma is due to lung metastasis. Despite the development of multi-agent chemotherapy and surgical resection, patients with osteosarcoma have a high metastasis rate and poor prognosis. Thus, it is necessary to identify novel therapeutic agents to improve the 5-year survival rate of these patients. Curcumin, a phytochemical compound derived from Curcuma longa, has been employed in treating several types of cancers through various mechanisms. Also, in vitro studies have demonstrated that curcumin could inhibit cell proliferation and induce apoptosis in osteosarcoma cells. Development in identifying signaling pathways involved in the pathogenesis of osteosarcoma has provided insight into finding new therapeutic targets for the treatment of this cancer. Targeting MAPK/ERK, PI3k/AKT, Wnt/β-catenin, Notch, and MircoRNA by curcumin has been evaluated to improve outcomes in patients with osteosarcoma. Although curcumin is a potent anti-cancer compound, it has rarely been studied in clinical settings due to its congenital properties such as hydrophobicity and poor bioavailability. In this review, we recapitulate and describe the effect of curcumin in regulating signaling pathways involved in osteosarcoma.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 1","pages":"71-82"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9509376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDO2-siRNA Carried by <i>Salmonella</i> Combined with Nifuroxazide Attenuates Melanoma Growth.","authors":"Tiesuo Zhao,&nbsp;Mengmeng Guo,&nbsp;Haoqi Chen,&nbsp;Lin Zhou,&nbsp;Jing Guo,&nbsp;Shenzhen Liu,&nbsp;Zizhong Wang,&nbsp;Wenshuai Huang,&nbsp;Qiang Zhang,&nbsp;Jiateng Zhong,&nbsp;Mingyong Wang,&nbsp;Huijie Jia,&nbsp;Yongxi Zhang","doi":"10.2174/1874467217666230329102030","DOIUrl":"https://doi.org/10.2174/1874467217666230329102030","url":null,"abstract":"<p><strong>Background: </strong>Melanoma, a highly malignant skin cancer, is a hot topic in oncology treatment research. Nowadays, tumor immunotherapy, especially immunotherapy combined with other therapies, has attracted more and more attention. Indoleamine 2,3-dioxygenase 2 (IDO2), a ratelimiting enzyme of the tryptophan metabolism pathway in the urine of dogs with immunosuppression, is highly expressed in melanoma tissue. Additionally, IDO2 significantly inhibits the anti-tumor immunity of the body and has become a novel target of melanoma treatment. Nifuroxazide, as an intestinal antibacterial agent, was found to be able to inhibit Stat3 expression and exert an anti-tumor effect. Therefore, the present study aimed to examine the therapeutic effect of a self-designed IDO2-small interfering RNA (siRNA) delivered by attenuated <i>Salmonella</i> combined with nifuroxazide on melanoma- bearing mice, as well as determine its underlying mechanism.</p><p><strong>Methods: </strong>The effect of nifuroxazide on melanoma was detected by flow cytometry, CCK-8 and colony- forming ability assays, respectively, <i>in vitro</i>. The plasmid of siRNA-IDO2 was constructed, and the mice-bearing melanoma model was established. After the treatment, the tumor growth and survival rate were monitored, and the morphological changes of tumor tissue were detected by HE staining. The expression of related proteins was detected by Western blotting, and the expression of CD4 and CD8 positive T cells in tumor tissue was detected by IHC and IF, and the proportion of CD4 and CD8 positive T cells in spleen was detected by flow cytometry.</p><p><strong>Results: </strong>The results demonstrated that the combination therapy effectively inhibited the phosphorylation of Stat3 and the expression level of IDO2 in melanoma cells, which effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice. The mechanistic study revealed that, compared with control groups and monotherapy groups, the combination treatment group reduced the atypia of tumor cells, increased the apoptotic rate, enhanced the infiltration of T lymphocytes in tumor tissue and increased the CD4⁺ and CD8⁺ T lymphocytes in the spleen, suggesting that the mechanism may be associated with the inhibition of tumor cell proliferation, the increase of apoptosis and the enhancement of the cellular immunity.</p><p><strong>Conclusion: </strong>In conclusion, IDO2-siRNA combined with nifuroxazide therapy could serve a significant role in the treatment of melanoma-bearing mice, enhance the tumor immunity and provide an experimental basis for identifying a novel combination method for the treatment of melanoma clinically.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":"16 8","pages":"881-893"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface","authors":"Michael Kahn","doi":"10.2174/187446721601221110105607","DOIUrl":"https://doi.org/10.2174/187446721601221110105607","url":null,"abstract":"It is currently estimated that 57 million people (1 in 4 adults) in the Unites States have prediabetes, many of whom will develop diabetes in ensuing years unless significant modifications in lifestyle occur, including diet, weight loss, and exercise. Furthermore, a small but significant number may already be at risk for developing vascular disease. Hence, prediabetes constitutes a major international public health concern that threatens to increase dramatically given the growing prevalence of worldwide obesity. Prediabetes is also associatedwith considerable financial expenditure with higher rates of medical visits for hypertension, metabolic and renal complications, and general medical conditions. The national annual medical cost of prediabetes has been estimated to exceed $25 billion. Since it therefore impacts considerably an already burdened healthcare system, the recently passed Affordable Care Act is opportune, as it addresses the critical need for preventive approaches to this epidemic. A major factor contributing to the difficulty in ascertaining who has prediabetes pertains to the way it, as diabetes per se, has been defined. As discussed in greater detail in this issue, the diagnosis of prediabetes hasbeenpredicated on absolute criteria defined by blood glucose measurements, which is one of the reasons the American Diabetes Association adopted a range of HbA1c values as a basis for identifying those at risk for developing diabetes. However, as neither glucose nor HbA1c determinations may be sufficiently sensitive to diagnose early metabolic abnormalities precisely, the practitioner requires considerable judgment in assessing these subtle conditions. Thus, defining prediabetes categorically by relatively arbitrary threshold criteria may inadvertently lead to the failure to diagnose individuals with lower glucose levels who may still be at risk for progression to diabetes or cardiovascular disease. Rather than viewing the evolving disease process as a continuum, the traditional dichotomous approach to definingmetabolic entitiesmost likely addresses only a small segment of a much larger problem and hence underestimates the considerable prevalence of this condition. One potential approach for overcoming the uncertainty associated with absolute diagnostic criteria is the use of a “personalized profile,” which would","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44915217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}