Clinical Science

Journal Information
ISSN / EISSN : 0143-5221 / 1470-8736
Published by: Portland Press Ltd. (10.1042)
Total articles ≅ 18,751
Current Coverage
SCOPUS
LOCKSS
MEDICUS
MEDLINE
PUBMED
SCIE
Archived in
EBSCO
SHERPA/ROMEO
Filter:

Latest articles in this journal

Hagit Shapiro, Kim Goldenberg, Karina Ratiner,
Published: 26 September 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1371-1387; https://doi.org/10.1042/cs20220175

Abstract:
Smoking is associated with an increased risk of cancer, pulmonary and cardiovascular diseases, but the precise mechanisms by which such risk is mediated remain poorly understood. Additionally, smoking can impact the oral, nasal, oropharyngeal, lung and gut microbiome composition, function, and secreted molecule repertoire. Microbiome changes induced by smoking can bear direct consequences on smoking-related illnesses. Moreover, smoking-associated dysbiosis may modulate weight gain development following smoking cessation. Here, we review the implications of cigarette smoking on microbiome community structure and function. In addition, we highlight the potential impacts of microbial dysbiosis on smoking-related diseases. We discuss challenges in studying host–microbiome interactions in the context of smoking, such as the correlations with smoking-related disease severity versus causation and mechanism. In all, understanding the microbiome’s role in the pathophysiology of smoking-related diseases may promote the development of rational therapies for smoking- and smoking cessation-related disorders, as well as assist in smoking abstinence.
Kai Jiang, Haiyan Chen,
Published: 26 September 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1367-1370; https://doi.org/10.1042/cs20220394

Abstract:
In the present commentary, we discuss new observations stating that angiopoietin-like protein 1 (ANGPTL1) attenuates cancer metastasis and stemness through Forkhead box O-3a (Foxo3a)–SRY-related HMG-box-2 (Sox2) axis in colorectal cancer (Clin. Sci. (2022) 136, 657–673, https://doi.org/10.1042/CS20220043). ANGPTL1 has been reported to play a critical role in cancer progression and metastasis. However, the underlying mechanisms remain controversial. Here, we integrate the possible mechanisms for ANGPTL1 inhibiting colorectal cancer liver metastasis and discuss the regulation of ANGPTL1 on the Foxo3a–Sox2 pathway. Although ANGPTL1 showed multifunctional potential, there is still a long way to go for ANGPTL1 to be an effective treatment strategy in the clinic.
Olufunto O. Badmus, Sarah A. Hillhouse, Christopher D. Anderson, ,
Published: 23 September 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1347-1366; https://doi.org/10.1042/cs20220572

Abstract:
The metabolic-associated fatty liver disease (MAFLD) is a condition of fat accumulation in the liver in combination with metabolic dysfunction in the form of overweight or obesity and insulin resistance. It is also associated with an increased cardiovascular disease risk, including hypertension and atherosclerosis. Hepatic lipid metabolism is regulated by a combination of the uptake and export of fatty acids, de novo lipogenesis, and fat utilization by β-oxidation. When the balance between these pathways is altered, hepatic lipid accumulation commences, and long-term activation of inflammatory and fibrotic pathways can progress to worsen the liver disease. This review discusses the details of the molecular mechanisms regulating hepatic lipids and the emerging therapies targeting these pathways as potential future treatments for MAFLD.
Jessica L. Faulkner,
Published: 16 September 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1341-1346; https://doi.org/10.1042/cs20220056

Abstract:
MicroRNA (miRNA) are small, single strand non-coding RNA molecules involved in the post-transcriptional regulation of target genes. Since their discovery in 1993, over 2000 miRNAs have been identified in humans and there is growing interest in both the diagnostic and therapeutic potential of miRNA. The identification of biomarkers for human disease progression remains an active area of research, and there is a growing number of miRNA and miRNA combinations that have been linked to the development and progression of numerous cardiovascular diseases, including hypertension. In 2010, Chen et al. reported in Clinical Science that cell-free circulating miRNA could serve as novel biomarkers for acute myocardial infarction [1]. In this commentary, we expand on this topic to discuss the potential of using miRNA as biomarkers for hypertension and hypertension-related end-organ damage.
, Charis Uhlson, Claire Palmer, Karin Zemski-Berry, Theresa L. Powell
Published: 14 September 2022
Journal: Clinical Science
Abstract:
Changes in placental lipid metabolism influence the delivery of lipids critical for fetal development and fetal requirements for lipids change across gestation. We hypothesized that placental lipid content and metabolic enzyme protein levels increase across gestation and are elevated in obesity. Placentas (4-40 weeks gestation) were collected from control (body mass index, BMI 18.5-24.9, n=37) and obese (BMI>30, n=19) pregnant women. Trophoblast villous tissue was homogenized and subjected to LC-MS/MS for phospholipid and triacylglycerol (TAG) analysis and western blot for protein quantification. The placental content of TAG species and 9 of 35 identified phosphatidylcholines (PC) were significantly higher (P<0.05) in first trimester (28-79%, 10-47%, respectively). Further, two TAG and three PC differed by maternal BMI and were significantly increased (P<0.05) in the obese group in first trimester (72-87%, 88-119%, respectively). Placental protein abundance of GPAT3 and AGPAT2, involved in de novo synthesis of PC and TAG, were higher (P<0.05) in the first trimester (66% and 74%, respectively). The protein abundance of the PC remodeling enzyme PLA2G4c was also higher (63%) in first trimester (P<0.05). In conclusion, the placental content of many phospholipid and TAG species and the protein level of associated synthesis enzymes are higher in first trimester human placenta. The high PC content may be related to the rapid membrane expansion in early pregnancy and the low placental oxygen tension may promote the accumulation of tissue TAGs in first trimester. Maternal obesity had only limited impact on placental lipid content and metabolic enzyme protein abundance.
Maria Florencia Albertoni Borghese, Lucas Humberto Oronel, Maria Del Carmen Ortiz,
Published: 8 September 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1303-1339; https://doi.org/10.1042/cs20220293

Abstract:
The developmental origin of hypertension and renal disease is a concept highly supported by strong evidence coming from both human and animal studies. During development there are periods in which the organs are more vulnerable to stressors. Such periods of susceptibility are also called ‘sensitive windows of exposure’. It was shown that as earlier an adverse event occurs; the greater are the consequences for health impairment. However, evidence show that the postnatal period is also quite important for hypertension and renal disease programming, especially in rodents because they complete nephrogenesis postnatally, and it is also important during preterm human birth. Considering that the developing kidney is vulnerable to early-life stressors, renal programming is a key element in the developmental programming of hypertension and renal disease. The purpose of this review is to highlight the great number of studies, most of them performed in animal models, showing the broad range of stressors involved in hypertension and renal disease programming, with a particular focus on the stressors that occur during the early postnatal period. These stressors mainly include undernutrition or specific nutritional deficits, chronic behavioral stress, exposure to environmental chemicals, and pharmacological treatments that affect some important factors involved in renal physiology. We also discuss the common molecular mechanisms that are activated by the mentioned stressors and that promote the appearance of these adult diseases, with a brief description on some reprogramming strategies, which is a relatively new and promising field to treat or to prevent these diseases.
Published: 5 September 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1257-1280; https://doi.org/10.1042/cs20211106

Abstract:
Individuals with severe psychiatric disorders, such as mood disorders and schizophrenia, are at increased risk of developing other medical conditions, especially cardiovascular and metabolic diseases. These medical conditions are underdiagnosed and undertreated in these patients contributing to their increased morbidity and mortality. The basis for this increased comorbidity is not well understood, possibly reflecting shared risks factors (e.g. lifestyle risk factors), shared biological mechanisms and/or reciprocal interactions. Among overlapping pathophysiological mechanisms, inflammation and related factors, such as dysbiosis and insulin resistance, stand out. Besides underlying the association between psychiatric disorders and cardiometabolic diseases, these mechanisms provide several potential therapeutic targets.
Published: 31 August 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1241-1255; https://doi.org/10.1042/cs20210990

Abstract:
Artery stenosis is a common cause of hypertension and stroke and can be due to atherosclerosis accumulation in the majority of cases and in a small fraction of patients to arterial fibromuscular dysplasia (FMD). Artery stenosis due to atherosclerosis is widely studied with known risk factors (e.g. increasing age, male gender, and dyslipidemia) to influence its etiology, including genetic factors. However, the causes of noninflammatory and nonatherosclerotic stenosis in FMD are less understood. FMD occurs predominantly in early middle-age women, a fraction of the population where cardiovascular risk is different and understudied. FMD arteriopathies are often diagnosed in the context of hypertension and stroke and co-occur mainly with spontaneous coronary artery dissection, an atypical cause of acute myocardial infarction. In this review, we provide a comprehensive overview of the recent advances in the understanding of molecular origins of FMD. Data were obtained from genetic studies using complementary methodological approaches applied to familial, syndromic, and sporadic forms of this intriguing arteriopathy. Rare variation analyses point toward mechanisms related to impaired prostacyclin signaling and defaults in fibrillar collagens. The study of common variation, mainly through a recent genome-wide association study, describes a shared genetic link with blood pressure, in addition to point at potential risk genes involved in actin cytoskeleton and intracellular calcium homeostasis supporting impaired vascular contraction as a key mechanism. We conclude this review with future strategies and approaches needed to fully understand the genetic and molecular mechanisms related to FMD.
, Brian Deskin, Mohammad Rehan, Santosh Yadav, Yasuka Matsunaga, Joseph A. Lasky,
Published: 31 August 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1229-1240; https://doi.org/10.1042/cs20210878

Abstract:
Fibrosis involving the lung may occur in many settings, including in association with known environmental agents, connective tissue diseases, and exposure to drugs or radiation therapy. The most common form is referred to as ‘idiopathic’ since a causal agent or specific association has not been determined; the strongest risk factor for idiopathic pulmonary fibrosis is aging. Emerging studies indicate that targeting certain components of aging biology may be effective in mitigating age-associated fibrosis. While transforming growth factor-β1 (TGF-β1) is a central mediator of fibrosis in almost all contexts, and across multiple organs, it is not feasible to target this canonical pathway at the ligand–receptor level due to the pleiotropic nature of its actions; importantly, its homeostatic roles as a tumor-suppressor and immune-modulator make this an imprudent strategy. However, defining targets downstream of its receptor(s) that mediate fibrogenesis, while relatively dispenable for tumor- and immune-suppressive functions may aid in developing safer and more effective therapies. In this review, we explore molecular targets that, although TGF-β1 induced/activated, may be relatively more selective in mediating tissue fibrosis. Additionally, we explore epigenetic mechanisms with global effects on the fibrogenic process, as well as metabolic pathways that regulate aging and fibrosis.
, Mariangela Scalise, Fabiola Marino, Luca Salerno, Nadia Salerno, Konrad Urbanek,
Published: 18 August 2022
Journal: Clinical Science
Clinical Science, Volume 136, pp 1179-1203; https://doi.org/10.1042/cs20220391

Abstract:
Cardiac muscle damage-induced loss of cardiomyocytes (CMs) and dysfunction of the remaining ones leads to heart failure, which nowadays is the number one killer worldwide. Therapies fostering effective cardiac regeneration are the holy grail of cardiovascular research to stop the heart failure epidemic. The main goal of most myocardial regeneration protocols is the generation of new functional CMs through the differentiation of endogenous or exogenous cardiomyogenic cells. Understanding the cellular and molecular basis of cardiomyocyte commitment, specification, differentiation and maturation is needed to devise innovative approaches to replace the CMs lost after injury in the adult heart. The transcriptional regulation of CM differentiation is a highly conserved process that require sequential activation and/or repression of different genetic programs. Therefore, CM differentiation and specification have been depicted as a step-wise specific chemical and mechanical stimuli inducing complete myogenic commitment and cell-cycle exit. Yet, the demonstration that some microRNAs are sufficient to direct ESC differentiation into CMs and that four specific miRNAs reprogram fibroblasts into CMs show that CM differentiation must also involve negative regulatory instructions. Here, we review the mechanisms of CM differentiation during development and from regenerative stem cells with a focus on the involvement of microRNAs in the process, putting in perspective their negative gene regulation as a main modifier of effective CM regeneration in the adult heart.
Back to Top Top