-
Cancer Epidemiology, Biomarkers &... Jun 2021Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence.
METHODS
We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies.
RESULTS
2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33; = 0.04].
CONCLUSIONS
Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence.
IMPACT
This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin.
Topics: Biomarkers; Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; Cancer Survivors; Diet, Healthy; Exercise; Female; Humans; Inflammation; Leptin; Neoplasm Recurrence, Local; Weight Loss
PubMed: 33737299
DOI: 10.1158/1055-9965.EPI-20-1029 -
Biomedicine & Pharmacotherapy =... May 2021All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected... (Meta-Analysis)
Meta-Analysis
Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies.
All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (M) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively.
Topics: Antiviral Agents; Catechols; Curcumin; Drug Repositioning; Fatty Alcohols; Humans; Medicine, Ayurvedic; Molecular Docking Simulation; Quercetin; SARS-CoV-2; Viral Proteins; COVID-19 Drug Treatment
PubMed: 33561649
DOI: 10.1016/j.biopha.2021.111356 -
American Journal of Physiology. Heart... Apr 2021Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise...
Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise generally improves endothelial function in a dose-dependent manner by altering hemodynamics, specifically by increased arterial pressure, pulsatility, and shear stress. However, athletes who regularly participate in high-intensity training can develop arterial plaques, suggesting alternative mechanisms through which excessive exercise promotes vascular disease. Understanding the mechanisms that drive atherosclerosis in sedentary versus exercise states may lead to novel rehabilitative methods aimed at improving exercise compliance and physical activity. Preclinical tools, including in vitro cell assays, in vivo animal models, and in silico computational methods, broaden our capabilities to study the mechanisms through which exercise impacts atherogenesis, from molecular maladaptation to vascular remodeling. Here, we describe how preclinical research tools have and can be used to study exercise effects on atherosclerosis. We then propose how advanced bioengineering techniques can be used to address gaps in our current understanding of vascular pathophysiology, including integrating in vitro, in vivo, and in silico studies across multiple tissue systems and size scales. Improving our understanding of the antiatherogenic exercise effects will enable engaging, targeted, and individualized exercise recommendations to promote cardiovascular health rather than treating cardiovascular disease that results from a sedentary lifestyle.
Topics: Animals; Arteries; Atherosclerosis; Bioengineering; Cells, Cultured; Computer Simulation; Disease Models, Animal; Endothelium, Vascular; Exercise Therapy; Hemodynamics; Humans; Microfluidic Analytical Techniques; Models, Cardiovascular; Plaque, Atherosclerotic; Sedentary Behavior
PubMed: 33385323
DOI: 10.1152/ajpheart.00719.2020 -
Frontiers in Oncology 2020Studies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.
BACKGROUND
Studies on the prognostic value of the soluble programmed death ligand 1 (sPD-L1) in cancer patients have not yielded consistent results.
OBJECTIVE
This meta-analysis was performed to assess the association between sPD-L1 and the prognosis of cancer patients.
METHODS
Published articles in Pubmed, EMBASE, and Cochrane clinical trial databases were searched from the inception to September 2020. Overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) data were evaluated using a hazard ratio (HR) at 95% confidence interval (95% CI).
RESULTS
A total 31 studies involving 17 tumors and 3,780 patients were included. The overexpression of sPD-L1 was associated with shorter OS (HR 1.85, 95% CI 1.59-2.15, I = 33%). High sPD-L1 had worse PFS (HR 2.40, 95% CI 1.55-3.72, I = 83%), and worse DFS (HR 2.92, 95% CI 2.02-4.29, I = 40%), without significant statistical difference in RFS (HR 2.08, 95% CI 0.99-4.40, I = 0%).
CONCLUSIONS
High sPD-L1 levels were associated with worse survival prognosis in cancer patients. The sPD-L1 may be a potential prognostic, non-invasive, and dynamic monitoring biomarker for cancers in the future.
PubMed: 33718120
DOI: 10.3389/fonc.2020.626932 -
Neuroscience and Biobehavioral Reviews Sep 2021Brain development is a dynamic and lengthy process that includes cell proliferation, migration, neurogenesis, gliogenesis, synaptogenesis, and pruning. Disruption of any... (Review)
Review
The importance of non-coding RNAs in environmental stress-related developmental brain disorders: A systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections.
Brain development is a dynamic and lengthy process that includes cell proliferation, migration, neurogenesis, gliogenesis, synaptogenesis, and pruning. Disruption of any of these developmental events can result in long-term outcomes ranging from brain structural changes, to cognitive and behavioral abnormality, with the mechanisms largely unknown. Emerging evidence suggests non-coding RNAs (ncRNAs) as pivotal molecules that participate in normal brain development and neurodevelopmental disorders. NcRNAs such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are transcribed from the genome but not translated into proteins. Many ncRNAs have been implicated as tuners of cell fate. In this review, we started with an introduction of the current knowledge of lncRNAs and miRNAs, and their potential roles in brain development in health and disorders. We then reviewed and discussed the evidence of ncRNA involvement in abnormal brain development resulted from alcohol, anesthetic drugs, nicotine, and viral infections. The complex connections among these ncRNAs were also discussed, along with potential overlapping ncRNA mechanisms, possible pharmacological targets for therapeutic/neuroprotective interventions, and potential biomarkers for brain developmental disorders.
Topics: Anesthetics; Brain Diseases; Humans; MicroRNAs; Nicotine; RNA, Untranslated; Virus Diseases
PubMed: 34186153
DOI: 10.1016/j.neubiorev.2021.06.033 -
Metabolites Sep 2023Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the... (Review)
Review
Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the systemic level by radiation and inflammation itself. Patients treated with RT due to head and neck cancer and patients with inflammation-related diseases located in the corresponding anatomical regions were selected. PubMed and Web of Science databases were searched from 1 January 2000 to 10 August 2023. Twenty-five relevant studies where serum/plasma metabolic profiles were analyzed using different metabolomics approaches were identified. The studies showed different metabolic patterns of acute and chronic inflammatory diseases, yet changes in metabolites linked to the urea cycle and metabolism of arginine and proline were common features of both conditions. Although the reviewed reports showed only a few specific metabolites common for early RT response and inflammatory diseases, partly due to differences in metabolomics approaches, several common metabolic pathways linked to metabolites affected by radiation and inflammation were revealed. They included pathways involved in energy metabolism (e.g., metabolism of ketone bodies, mitochondrial electron transport chain, Warburg effect, citric acid cycle, urea cycle) and metabolism of certain amino acids (Arg, Pro, Gly, Ser, Met, Ala, Glu) and lipids (glycerolipids, branched-chain fatty acids). However, metabolites common for RT and inflammation-related diseases could show opposite patterns of changes. This could be exemplified by the lysophosphatidylcholine to phosphatidylcholine ratio (LPC/PC) that increased during chronic inflammation and decreased during the early phase of response to RT. One should be aware of dynamic metabolic changes during different phases of response to radiation, which involve increased levels of LPC in later phases. Hence, metabolomics studies that would address molecular features of both types of biological responses using comparable analytical and clinical approaches are needed to unravel the complexities of these phenomena, ultimately contributing to a deeper understanding of their impact on biological systems.
PubMed: 37755280
DOI: 10.3390/metabo13091000 -
Antibiotics (Basel, Switzerland) Mar 2023The dissemination of -harboring (KPC-) is considered a serious public health problem. This study provides an overview of the epidemiology of these isolates to try to... (Review)
Review
The dissemination of -harboring (KPC-) is considered a serious public health problem. This study provides an overview of the epidemiology of these isolates to try to elucidate novel mobilization platforms that could contribute to their worldwide spread. A systematic review in PubMed and EMBASE was performed to find articles published up to June 2022. In addition, a search algorithm using NCBI databases was developed to identify sequences that contain possible mobilization platforms. After that, the sequences were filtered and pair-aligned to describe the genetic environment. We found 691 KPC- isolates belonging to 41 different sequence types and recovered from 14 countries. Although the gene is still mobilized by the transposon Tn, the non-Tn elements (NTE) were the most frequent. Our analysis allowed us to identify 25 different NTE, mainly belonging to the NTE-I, and a new type (proposed as IVa) was also observed. This is the first systematic review that consolidates information about the behavior of the acquisition in and the genetic platforms implied in its successful worldwide spread. Our results show high NTE prevalence in and an accelerated dynamic of unrelated clones. All information collected in this review was used to build an interactive online map.
PubMed: 37107020
DOI: 10.3390/antibiotics12040658 -
International Journal of Molecular... Oct 2023With more than 466 million people affected, hearing loss represents the most common sensory pathology worldwide. Despite its widespread occurrence, much remains to be... (Review)
Review
With more than 466 million people affected, hearing loss represents the most common sensory pathology worldwide. Despite its widespread occurrence, much remains to be explored, particularly concerning the intricate pathogenic mechanisms underlying its diverse phenotypes. In this context, metabolomics emerges as a promising approach. Indeed, lying downstream from molecular biology's central dogma, the metabolome reflects both genetic traits and environmental influences. Furthermore, its dynamic nature facilitates well-defined changes during disease states, making metabolomic analysis a unique lens into the mechanisms underpinning various hearing impairment forms. Hence, these investigations may pave the way for improved diagnostic strategies, personalized interventions and targeted treatments, ultimately enhancing the clinical management of affected individuals. In this comprehensive review, we discuss findings from 20 original articles, including human and animal studies. Existing literature highlights specific metabolic changes associated with hearing loss and ototoxicity of certain compounds. Nevertheless, numerous critical issues have emerged from the study of the current state of the art, with the lack of standardization of methods, significant heterogeneity in the studies and often small sample sizes being the main limiting factors for the reliability of these findings. Therefore, these results should serve as a stepping stone for future research aimed at addressing the aforementioned challenges.
Topics: Animals; Humans; Reproducibility of Results; Hearing Loss; Deafness; Metabolomics; Metabolome
PubMed: 37894867
DOI: 10.3390/ijms242015188 -
Clinical Medicine & Research Dec 2020Huntington's disease (HD)(MIM:143100) is an severe autosomal dominant neurodegenerative disease caused by the dynamic expansion of CAG trinucleotides (> 35) in the gene... (Review)
Review
BACKGROUND
Huntington's disease (HD)(MIM:143100) is an severe autosomal dominant neurodegenerative disease caused by the dynamic expansion of CAG trinucleotides (> 35) in the gene [Genomic Coordinates- (GRCh38):4:3,074,680-3,243,959].
OBJECTIVES
The aim of this systematic review was to investigate the reported associations between the frequencies of the A1 and A2 haplotypes in HD-affected and non-affected populations from different countries on different continents, in order to demonstrate the overall profile of these haplotypes worldwide, pointing towards the most frequent haplotypes that could be useful for mutant-specific allele silencing in different populations.
METHODS
Publications in MEDLINE (PubMed) and Embase from the last 10 years (PROSPERO CRD42018115282) were assessed.
RESULTS
A total of 20 articles from 113 were selected for evaluation in their entirety, and eight were eligible for this study.
CONCLUSION
Regardless of the size of the CAG tract, the articles included in this review demonstrate that populations with high HD prevalence present higher frequencies of the A1 or A2 haplotypes than populations exhibiting low HD prevalence, even when similar average CAG numbers are noted. Based on the presented articles, we suggest that the haplotypic profile is more closely related to the ancestral origin than to the size of the CAG tract. The identification of populations presenting a higher frequency of high-risk genotypes can contribute to more accurate genetic counseling, in addition to providing knowledge on HD epidemiology. According to the continued progress in the development of specific genetic silencing therapies by different research groups and pharmaceutical companies, such as haplotype targeting strategies for allele-specific suppression, we conclude that the definition of haplotypes in phase with CAG expansions will contribute to the design of gene-silencing drugs specific for different populations worldwide.
Topics: Alleles; Haplotypes; Humans; Huntingtin Protein; Huntington Disease; Neurodegenerative Diseases
PubMed: 32878904
DOI: 10.3121/cmr.2020.1523 -
Tomography (Ann Arbor, Mich.) Nov 2022Breast cancer patients who have pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) are more likely to have better clinical outcomes. The ability to... (Review)
Review
Breast cancer patients who have pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) are more likely to have better clinical outcomes. The ability to predict which patient will respond to NAC early in the treatment course is important because it could help to minimize unnecessary toxic NAC and to modify regimens mid-treatment to achieve better efficacy. Machine learning (ML) is increasingly being used in radiology and medicine because it can identify relationships amongst complex data elements to inform outcomes without the need to specify such relationships a priori. One of the most popular deep learning methods that applies to medical images is the Convolutional Neural Networks (CNN). In contrast to supervised ML, deep learning CNN can operate on the whole images without requiring radiologists to manually contour the tumor on images. Although there have been many review papers on supervised ML prediction of pCR, review papers on deep learning prediction of pCR are sparse. Deep learning CNN could also incorporate multiple image types, clinical data such as demographics and molecular subtypes, as well as data from multiple treatment time points to predict pCR. The goal of this study is to perform a systematic review of deep learning methods that use whole-breast MRI images without annotation or tumor segmentation to predict pCR in breast cancer.
Topics: Humans; Female; Breast Neoplasms; Deep Learning; Magnetic Resonance Imaging; Breast; Neoadjuvant Therapy
PubMed: 36412691
DOI: 10.3390/tomography8060232