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May 2024 DOI 10.14302/issn.2470-0436.jos-23-4493
Background Beta-Sitosterol (SIT) is an active TCM compound employed to treat diabetic retinopathy (DR). A network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying DR has not been pursued. Methods The potential targets for DM were identified according to the MedGene, Gendome, HGNC, OMIM, GeneCards, PheGenI, GEO, and STRING database. The herb and components were predicted and screened by network pharmacology through oral bioavailability and drug-likeness filtration using the Traditional Chinese Medicine Systems Pharmacology Analysis Platform database. A network pharmacology prediction and network analysis were used to predict the active potential targets and pathways of SIT application to DR. Results We found the Top 15 DR-related genes by screening in 9 databases. 26 kinds of TCM and nearly 300 kinds of active ingredients. SIT exists in 10 kinds of DR-treat TCM. The comprehensive network pharmacology approach was successful in identifying 23 kinds of core genes for SIT treating DR. ERBB3 and IGF2-related PI3K-Akt signaling pathway or EDN3, IGF2 and SPP1-related receptor ligand activity pathway might be the main pharmacological targets, and pathways in DR. We speculated that SIT was effective for the treatment of DR. Conclusion Based on the network pharmacology, we predicted the potential targets of SIT in treating DR and helped to illustrate the mechanism of action. Our study identifies key genes and pathways associated with the prognosis and pathogenesis of DR from new insights.
Nov 2018 DOI 10.14302/issn.2574-4488.jna-18-2443
Renal fibrosis was a chronic and progressive process affecting kidneys in chronic kidney disease (CKD), regardless of cause. Although no effective targeted therapy yet existed to retard renal fibrosis, a number of important recent advances have highlighted the cellular and molecular mechanisms underlying the renal fibrosis. The advances including TGF-β/Smad pathway, oxidative stress and inflammation, hypoxia and gut microbiota-derived from uremic solutes were highlighted that could provide therapeutic targets. New therapeutic targets and strategies that are particularly promising for development of new treatments for patients with CKD were also highlighted.
Mar 2016 DOI 10.14302/issn.2470-5020.jnrt-15-800
Although clinical trials in refractory epilepsy are currently carried out, the field of deep brain stimulation (DBS) in epilepsy is still at its initial stage. Little is known about where, when and how to stimulate and what would be the short and long consequences. Animal studies might provide clinicians with new ideas regarding targets for DBS. Here an overview is given regarding old and new targets in rodent models of temporal lobe epilepsy. The evidence from animal models showed that stimulation of the subiculum – either in responsive or scheduled manner - is anticonvulsant in different seizure and epilepsy models, indicating that the subiculum might be a promising candidate for DBS targets. For the rest, the antiepileptic effects of low frequency stimulation were established mostly in kindling models. The presence of a critical time window in which stimulation was effective following after discharges on kindling acquisition, demonstrates that timing of DBS is an important factor for the anticonvulsant effects of DBS.
Dec 2025
The incidence rate of melasma is notably high among patients with anxiety disorders. Aromatherapy primarily influences the physiological and psychological states of individuals through the inhalation or application of essential oils, thereby facilitating the treatment or alleviation of various conditions. This study aims to explore the action mechanism of complex lemon-angelica sinensis -boswellia essential oil (CEO) in treating anxiety disorders with melasma. We investigated the active ingredients, targets, and pathways of CEO in relation to anxiety and melasma using network pharmacology. We employed cell assays and conducted nebulized essential oil inhalation tests on CUMS mice to validate the intervention effects of CEO on anxiety. A total of 28 active components, including neryl acetate, 3-butenylphthalide and octyl acetate, and 26 cross-targets, such as ESR1, CCND1 and PIK3CA, were identified. GO and KEGG pathway analyses indicated that these cross-targets were primarily involved in endocrine regulation, cell proliferation, and apoptosis, specifically through PI3K/Akt signaling pathway and calcium signaling pathway. The experimental results demonstrated that CEO significantly reduced the secretion of NO, TNF-a and IL-6, as well as the mRNA expressions of ESR1, CCND1 and PIK3CA in cells compared to the inflammatory cell model. Furthermore, CEO notably decreased the forced swimming immobility time of mice and the levels of IL-1β, ESR1 and CCND1 in hippocampus when compared to model mice. These findings suggest that CEO may regulate ESR1, CCND1 and PIK3CA through its citral, 3-butylphthalate and neryl acetate, thereby influencing endocrine function, cell proliferation and apoptosis, inhibiting inflammation and anxiety-like behavior in CUMS-induced mice.
Nov 2025 DOI 10.14302/issn.2326-0793.jpgr-25-5573
Advancements in proteomic and genomic technologies have transformed molecular biology by enabling comprehensive analysis of biological systems at the molecular level. This literature review explores the evolution, methodologies, and practical applications of key proteomic and genomic techniques. In proteomics, tools such as two-dimensional electrophoresis, mass spectrometry, Western blotting, Edman degradation, and functional protein microarrays have facilitated high-throughput protein identification, post-translational modification analysis, and biomarker discovery. Similarly, genomic methodologies like PCR, recombinant DNA technology, gel electrophoresis, and Southern blotting have revolutionized gene detection, manipulation, and expression profiling. The review also highlights the interdisciplinary impact of these technologies across clinical diagnostics, oncology, autoimmune disorders, infectious disease surveillance, cardiovascular research, and personalized nutrition. Integrative approaches combining proteomics and genomics are enabling the discovery of novel therapeutic targets, improving disease classification, and advancing precision medicine. Despite current limitations, such as the absence of amplification techniques for proteins and challenges in data interpretation, ongoing innovations promise to bridge these gaps. This synthesis underscores the pivotal role of molecular techniques in deepening our understanding of human biology and accelerating biomedical advancements for improved healthcare outcomes.
Nov 2025
Frequency neurofeedback (FNF) is a biofeedback method that targets frequencies between 1 and 50 Hz. The efficacy of FNF with autism has been labeled ‘probably efficacious’ in literature reviews in the last decade, despite new research pointing towards a higher standard. The aim of this review was to analyze key features of these studies, with a goal of determining the efficacy standard of FNF on autism and establishing a research direction. Electronic databases and literature reviews were used to collect a total of ten randomized and/or matched controlled trials. FNF reaches a Level 4 efficacy standard, with an impact on a broad range of factors including core autistic traits, social communication, emotional regulation, cognitive flexibility, executive function, behaviors of concern, attention, metabolic or thermal activity, and EEG e.g. decreased absolute power, mu rhythm, coherence and hyperconnectivity. Current evidence generalizes to male children, up to 18 years, with a low-average or higher intellectual functioning, with autism as the only diagnosis. A meta-analysis suggests a large superior effect when compared to wait list controls. Current research does not meet the higher efficacy standards outlined by Arns et al. (2020). Small samples plague most studies, and the maintenance of improvements post-training are yet to be assessed adequately. Eight recommendations are made.
Nov 2025 DOI 10.14302/issn.2693-1176.ijgh-25-5745
Background Healthcare worker stress, anxiety, burnout, and trauma have been widely documented across global healthcare systems. Staff in maternal and neonatal units frequently encounter emotionally distressing events and work under high pressure with limited resources. In Zambia, despite some gains in reducing maternal and neonatal mortality, fatality rates remain above national targets, exposing staff to repeated occupational trauma. Objective(s) This study aimed to assess the psychological well-being of staff in maternal and neonatal intensive care units, identify specific needs and stressors, and develop practical recommendations to improve resilience and support staff mental health. Methods A mixed-methods cross-sectional study was conducted at Ndola Teaching Hospital (NTH) and Arthur Davison Children's Hospital (ADCH), two major tertiary hospitals in Zambia. Data were collected over four days in February 2025. The study included 87 (out of 161) healthcare professionals, including nurses, midwives, and doctors. The Goldberg Anxiety and Depression Scale (GADS) and the Professional Quality of Life Scale Version 5 (ProQOL 5) were used to collect quantitative data, which were analysed using descriptive statistics and 95% confidence intervals (CI). Open-ended survey questions provided qualitative data, which were analysed using thematic analysis. Ethical approval was granted by the hospital ethics committee. Results High rates of clinical symptoms were observed. The overall prevalence of symptoms in the past 30 days was: anxiety (62%), depression (68%), burnout (50%), and secondary traumatic stress (46%). Junior doctors demonstrated the highest rates of depression (83%) and burnout (67%). The obstetrics and gynaecology and labour wards had the highest rates of secondary traumatic stress symptoms. Key qualitative themes identified were professional stressors, team and leadership issues, and the emotional burden of the work. Conclusion This study highlights an urgent need for both psychological and organizational support for maternal and neonatal healthcare staff in Zambia. The findings indicate that burnout and secondary traumatic stress are highly prevalent, particularly among junior doctors and those in high-risk wards. Targeted interventions at both systemic and individual levels are necessary to protect the well-being of healthcare workers and improve patient outcomes.
Jan 2024 DOI 10.14302/issn.2574-4496.jtc-23-4835
The prevalence of thyroid cancer is rapidly increasing worldwide, majorly due to overdiagnosis and overtreatment methods of differentiated thyroid cancer. The emergent and potent preclinical models, high-throughput molecular techniques, and genetic expression microarrays have delivered deeper insights into understanding the molecular features in oncogenesis. Thus, molecular markers have become a promising tool in managing thyroid cancer for differentiating benign and malignant tumors, prognosis, recurrence, and determination of novel therapeutic targets. In differentiated thyroid cancer, molecular markers are majorly utilized for guiding the development of indeterminate thyroid nodules on fine needle aspiration (FNA) histologies. Dissimilar to this, in advanced thyroid cancer, molecular markers permit targeted treatment of a modified signaling cascade. Determining causal mutation of targeted kinase receptors in advanced thyroid cancer can depict a promising treatment strategy with mutation-targeted tyrosine kinase inhibitors to reduce progression and eradicate mutation effects when conventional methods fail to manage. This review will focus on the molecular landscape and discuss the impact of molecular markers on the prognosis, treatment, and surveillance of differentiated and anaplastic thyroid cancer.
Apr 2023 DOI 10.14302/issn.2643-2811.jmbr-23-4528
Rapidly spreading Covid-19 virus and its variants, especially in metropoli- tan areas around the world, became a major health public concern. The tendency of Covid-19 pandemic and statistical modelling represent an urgent challenge in the United States for which there are few solutions. In this paper, we demonstrate com- bining Fourier terms for capturing seasonality with ARIMA errors and other dynamics in the data. Therefore, we have analyzed 156 weeks COVID-19 dataset on national level using Dynamic Harmonic Regression model, including simulation analysis and ac- curacy improvement from 2020 to 2023. Most importantly, we provide a new advanced pathways which may serve as targets for developing new solutions and approaches.
Dec 2022 DOI 10.14302/issn.2328-0182.japst-22-4363
The process of creating new pharmaceuticals is incredibly costly and time-consuming, and it dates back millions of years to the time when only herbal remedies were used. Furthermore, the solvation energies of the ligand and receptor site are crucial to this process because partial to complete dedication must take place before binding. The full form of CADD is computer-added drug design. To enhance the design and discovery of, CADD stands for computational methodologies and resources. Smaller numbers of chemicals are chosen from extensive compound libraries for experimental testing. There is less screening. Pharmacogenomics’ main benefit is the ability to develop medication based on the genomiy organization of each individual. The immense potential of enzymes as therapeutic targets is exemplified by under R's leadership, Merck's strategy. Both the two exemplary PP'S were the (APS, a class of proteins, are making progress it will blossoms in computational thermodynamics.3D-QSAR mode was developed last year for the follow-up forecast of action of chemicals in a molecular database or newly created target's spatial organization is known.
May 2021 DOI 10.14302/issn.2689-4602.jes-21-3837
The coronavirus infectious disease (20)19 (COVID-19) pandemic is caused by a newly identified virus (2019) SARS-CoV-2, a beta coronavirus that shares similarities with other human-infecting coronaviruses. Genomic analysis suggests that SARS-CoV-2 is closely related to SARS-CoV, a bat-related coronavirus, RaTG13, and to other pangolin-associated coronaviruses. The spike protein of coronaviruses are glycoproteins and are responsible for attaching the virus to the host cell and entering. Amino acid changes within the spike protein-encoding gene from SARS-CoV to SARS-CoV-2 enable SARS-CoV-2 to form a stable spike protein, to form a stable complex between the S protein and the receptor ACE2, to increase binding points between the S protein and ACE2, and to survive at higher temperatures. SARS-CoV-2 is zoonotic, with genomic analysis implicating bats as the original host and pangolins as the most likely intermediate host to infect humans. As SARS-CoV-2 infects humans, viral point mutations will continually occur and cause the emergence of new competitive SARS-CoV-2 strains. Two major strains include D614G and N501Y and have increased infectivity and transmission, further complicating the scope of the current COVID-19 pandemic. Vigilant monitoring of viral development and evolution is necessary for developing proper treatment methods and vaccine targets.
Jan 2020 DOI 10.14302/issn.2639-3166.jar-20-3165
This commentary questions the presumption of ever‑increasing crop productivity as the singular goal. It weighs diminishing returns and ecological costs against diversification, efficiency, and demand‑side measures. The authors argue for context‑specific targets that prioritize nutrition, resilience, and sustainability over yield expansion alone.
Sep 2019 DOI 10.14302/issn.2471-2140.jaa-19-2997
The paper explores the formation of a-oxoaldehydes during the interaction of glucose metabolites with hydroxyl or alkoxyl radicals. Hydroxyl radicals were generated under radiolysis of aqueous solutions, and alkoxyl radicals (t-BuO) were obtained in the model system tert-butyl hydroperoxide/Fe2+. High-performance liquid chromatography revealed that methylglyoxal was one of the organic products resulting from t-BuO-induced transformations of fructose-1,6-bisphosphate under hypoxic conditions. The interaction of lysine and methylglyoxal one of the main targets of a-oxoaldehydes in proteins was also studied. As chemiluminescence and EPR spectroscopy demonstrated, this reaction generates a methylglyoxal anion radical, a cation-radical of methylglyoxal dialkylamine and a superoxide anion radical. EPR signal of methylglyoxal-derived free radicals was observed in hypoxia, whereas only the trace amounts of these free radicals were recorded in the aerated reaction medium.
Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2973
Head and Neck cancer (HNC) is one of the most prevalent and lethal cancer globally. The incidence of tobacco-induced HNC is gradually increasing in low and middle income countries. Among the various causative factors associated with HNCs, tobacco and alcohol play synergistic effect and are frequently associated with the risk of HNC. Tobacco-induced HNCs show distinct genetic and epigenetic alterations leading to different clinical outcomes in comparison to HPV-infected HNCs. Tobacco-induced HNCs are often associated with tumor aggressiveness, poor prognosis and low or nil prevalence of HPV infection. Apart from carcinogenic effects of these causative factors (use of tobacco products, alcohol intake and HPV or EBV infections), recent studies show that exposure to these factors alter/disrupt the regulation of non-coding RNAs including the long non-coding RNAs (lncRNAs). Altered lncRNA regulation is brought about by signalling networks that regulate cellular differentiation, apoptosis, angiogenesis and inflammatory pathways which play key functions in the genesis of different cancers including HNCs. There are numbers of studies supporting the emerging role of lncRNAs in development of HNC; however, reports connecting lncRNAs expression and addiction habits in HNC are still preliminary and sparse. Therefore, identification and characterization of lncRNAs that are differentially expressed upon exposure to risk-factors can serve as unique therapeutic targets and potential biomarker(s) for effective treatment of HNC subtypes. In this short review, we briefly reviewed the emerging role of lncRNAs in tobacco and alcohol induced HNCs.
Jun 2019 DOI 10.14302/issn.2379-7835.ijn-19-2845
The mangosteen fruit is a popular Southeast Asian fruit consumed for centuries. There have been a variety of xanthones isolated from the fruit, bark, roots and leaves with each having unique chemical and physical properties. Previously, the most abundant xanthone α-mangostin has been shown to inhibit CDK4. Herein we describe the role of selected xanthones from the mangosteen inhibiting CDK4. The evidence we provide here is that key functional groups are required to inhibit the CDK4 protein to prevent the phosphorylation of downstream targets critical to inhibiting uncontrolled cell cycle progression. To define the properties of xanthones for inhibiting CDK4 we utilized a cell free biochemical assay to identify inhibitors of CDK4. The following xanthones were used for the analysis: α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinone C and garcinone D, 9-hydroxycalabaxanthone, and 3-isomangostin These results further substantiate the unique pharmacological properties of individual xanthones and how a mixture of xanthones may be responsible for a multi-targeted effect in cell based pharmacology systems.
Jun 2019 DOI 10.14302/issn.2688-5328.ijp-19-2731
The rise of epigenetics provides a new idea for studying the regulation of chronic pain-related genes and synaptic plasticity. External environmental stimuli can regulate BDNF genes through different epigenetic modifications. The epigenetic changes of the BDNF gene can affect the expression of its mRNA and protein and participate in the development of chronic pain. By reviewing the literature, this paper reviews the mechanism of epigenetic regulation of brain-derived neurotrophic factor (BDNF) in chronic pain, which provides some new directions and targets for the treatment of chronic pain.
Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2578
We present below a mechanistic cellular and molecular approaches for the development of Anti-Inflammatory biomarkersof Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses approaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory pathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary components on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.
Jan 2019 DOI 10.14302/issn.2641-5526.jmid-18-2529
Discrimination of case-control status based on gene expression differences has potential to identify novel pathways relevant to neurodegenerative diseases including Parkinson’s disease (PD). In this paper we applied two different novel algorithms to predict dysregulated pathways of gene expression across several different regions of the brain in PD and controls. The Fisher’s ratio sampler uses the Fisher’s ratio of the most discriminatory genes as prior probability distribution to sample the genetic networks and their likelihood (accuracy) was established via Leave-One-Out-Cross Validation (LOOCV). The holdout sampler finds the minimum-scale signatures corresponding to different random holdouts, establishing their likelihood using the validation dataset in each holdout. Phenotype prediction problems have by genesis a very high underdetermined character. We used both approaches to sample different lists of genes that optimally discriminate PD from controls and subsequently used gene ontology to identify pathways affected by disease. Both algorithms identified common pathways of Insulin signaling, FOXA1 Transcription Factor Network, HIF-1 Signaling, p53 Signaling and Chromatin Regulation/Acetylation. This analysis provides new therapeutic targets to treat PD.
Jan 2019 DOI 10.14302/issn.2643-0282.imsj-18-2448
Fungal infections increased substantially in the last years, becoming a relevant public health problem. Many of these infections account for high rates of morbidity and mortality. The emergence of resistant fungal clinical isolates have also motivate studies to find new antifungal therapies. Candida albicans is an oportunistic pathogen and affects a great number of immunocompromised patients worldwide. The marine ecosystem has been considered a rich source of bioactive metabolites due to the complexity and originality of its structures. Proteins and peptides from marine organisms have been shown to have antiviral, anti-inflammatory, antimalarial, anticancer, antimicrobial and antifungal properties. Arenicins are antimicrobial peptides isolated from the marine lugworm Arenicola marina with 21 amino acid residues in a β-hairpin structure. Dihydrofolate reductase, exo-b-(1,3)-glucanase and sterol 14α-demethylase are essential C. albincas enzymes that take part in DNA, cell wall and membrane metabolism, respectively. The present study evaluates the interaction of arenicin with important enzymes of C. albicans related to cell wall, ergosterol and DNA metabolism in order to elucidate possible molecular targets. We showed through an in silico approach, that a single compound from a marine worm (A. marina), can bind to three C. albicans essential proteins. The interaction occurs in regions inside the active site or at least near, with amino acid residues evaluated as hot spots. Arenicin is a new promising antifugal drug. The next step is to investigate protein-protein interactions performed by DHFR, EBG and CYP51 and assess whether arenicin is able to disrupt essential interaction or not.
Aug 2018
Drug design, referred to the fields of pharmacology, biotechnology and medicine, is in silico, in vitro and in vivo assay processes of finding new candidate medications based on the biological targets. The in silicoexperiments of drug discovery are involved in the macromolecular structure databases, small molecule databases, molecular docking, de novo drug design and molecular dynamics simulations. The in vitro experiments of drug discovery need evaluate the direct interaction information between ligands and targets as well as the function of ligands on signaling pathway in the cell. The in vivo experiments of drug discovery give the convincing evidence for preclinical trial at the physiological level. In this review, we outline the drug design components of databases, virtual screening tools, biochemical assays, cell-based system and animal models.
Aug 2018 DOI 10.14302/issn.2639-1716.jn-18-2208
Breast cancer (BC) is the leading cause of cancer-related deaths in young to middle-aged women worldwide. Moreover, the survival rate in BC-patients is only 20% when associated with metastatic disease. The high mortality rate observed in BC women with metastatic disease has precipitated a major challenge revealing an unmet need to develop new therapeutic strategies in treating metastatic cancer. One such approach has involved utilization of chemokines and their receptors as therapeutic targets for cancer metastasis. It has been established that a definitive correlation exists between overexpressed CXCR4 malignant cell receptors and cancer cell growth, invasion, and migration. It is also widely accepted that the CXCR4 receptor, complexed to its CXCL12 ligand, plays a major role in establishing migratory pathway gradients for cancer cells migrating to distant tissues/organ sites. It would follow that chemokine decoy ligands, such as peptide antagonists and inhibitors, could serve to induce receptor blockade and impede subsequent intracellular signaling. Such ligands, synthetic and natural, reportedly contribute to reducing cancer cell growth, invasion, adherence, and migration. The present commentary describes several existing synthetic CXCR4 receptor-ligand peptide antagonists and presents a strategy to develop naturally-occurring human protein-derived peptide candidates.
May 2018 DOI 10.14302/issn.2832-5311.jpcd-18-2077
Polysaccharide transglycosylases (PTGs) are a unique group of glycoside hydrolases playing important roles in the formation and modification of plant and fungal cell walls. Their action involves cutting the molecule of the polysaccharide substrate at the glycosidic bond, followed by transfer of the newly formed reducing-end fragment to the non-reducing end of another polysaccharide molecule, with the formation of a new glycosidic bond. As there is no net increase in the number of reducing ends in the system, conventional reductometric methods used to assess the activity of glycoside hydrolases are ineffective. Since the PTGs participate in vital processes, such as the elaboration of cell walls in plants and fungi, and are not present in animal cells, they are considered as possible targets for future specific fungicides and herbicides. Biochemical studies of PTGs, as well as the search for their inhibitors, require the availability of convenient and efficient methods for their assay. In this review we briefly describe the principles of methods used to detect and to determine the activity of this important group of enzymes.
Apr 2018
Heart failure(HF) is a disease with high morbility and mortality. The benefits of current pharmacological and device therapy for survival outcomes of patients with HF are limited. Gene therapy represents a novel promising strategy in treating HF, as it can theoretically normalize the aberrantly expressed genes and their regulatory mechanisms permanently. However, the translation of gene therapy for HF from bench to bedside has been less successful. There are many challenges ahead for gene therapy, especially in the areas of selection of the optimal targets, the needs for developing delivery systems and the improvement in design of clinical trials. In this review, we summarize the most promising gene targets which have been used in experimental and clinical studies for treating HF, highlighting the results from several clinical trials. We also review the latest development in gene therapy vectors and delivery methods, aiming to provide directions for future studies.
Aug 2017 DOI 10.14302/issn.2474-3585.jpmc-17-1591
Background: There are relatively few research publications of mental health promotion initiatives for primary school aged children that are based in community rather than educational settings. Aims: To describe developmental frameworks and models of mentoring, coaching and mental health promotion and to summarize any evidence for the efficacy of community initiatives. Methods: An umbrella review was undertaken of publications on theories and models, and a synthesis of findings from reviews of outcomes of mentoring, mental health promotion initiatives undertaken outside of school time for children aged 5-11 years. Results: Developmental mentoring on its own or in combination with outside school activities is potentially more flexible in terms of delivery and targets than school-based programs. Pooled effect sizes (range about 0.2-0.4) suggest modest but significant gains across several key domains (cognition, emotion, physical health, and social connectedness) that equate to about 10 percentile point on the developmental evaluations employed. Mediators of benefits include the level environmental or individual risk of the child and parental involvement. It is noteworthy that poor quality, atheoretical programs can have detrimental effects. Conclusions: Children aged 5-11 years may be more accepting of, and could make significant gains from, community-based mental health promotion interventions such as developmental mentoring. However, there are some significant gaps in the knowledge-base that need to be addressed through more systematic research.
Jun 2017 DOI 10.14302/issn.2329-9487.jhc-17-1536
Over the last few decades, many research works highlighted the role of miRNAs on cardiac diseases. Ischaemic heart disease (IHD) or coronary heart disease is a condition that is mainly caused by atherosclerosis. It has been established that microribonucleic acids regulate many factors that are involved in the development and pathophysiology of IHD. As a result, there are great potential opportunities for miRNAs to be used as a biomarker for disease differentiation, as well as novel drug targets or therapeutics for the treatment and also as a diagnostic approach. As it is now evident that miRNAs play critical roles in the disease mechanisms, this review article tried to focus on the pathway, in which; the miRNAs stimulate the IHD to develop. By understanding the mechanisms, it will be possible to present a complete strategy of IHD treatment and also solving all the impediments that are highlighted in this article. Still, there are a number of limitations and obstacles on the way of developing a proper therapeutic approach that can be approved and well accepted. This review is mainly dependent on the potential of miRNAs as a promising arena on the field of cardiac treatment and the possible obstacles that are needed to be explored and overcome.
Apr 2017 DOI 10.14302/issn.2470-0436.jos-17-988
Photorefraction (PR) methods have beenwidely used for pediatric vision screening since the 1980’s. While PR is easy to implement, the accuracy of refractive error measurements in humans has been unsatisfactory, largely due to the variations of intraocular scattering, the retinal reflectance, and pupil size. The objective of our studies was to clinically evaluate the accuracy of refraction measurements of an improved PR-based device, the Dynamic Ocular Evaluation System (DOES), and to investigate whether the accuracy is affected by the patient’s age, race, and pupil size, which are relevant to individual intraocular scattering and retinal reflectance. We performed DOES measurements in 99 volunteers (198 eyes) under two environmental light conditions and using four fixation targets. These results were compared to the standard clinical refraction testing performed the same day. The correlation and standard deviation were determined by Bland-Altman analysis. The influence of intraocular scattering, retinal reflectance, and pupil size was evaluated by comparing results from different age groups, races, and lighting conditions. In the region between -4 diopter (D) and +4D, the device showed a binocular refraction measurement accuracy of 0.45 D, 0.3 D, and 0.18 D root-mean-square (RMS) error (n=1337) for spherical equivalent and cross cylinders Jo and J45, respectively. Inaccuracy increased at high refraction (>4D). Age, race, and pupil size did not appear to significantly affect DOES PR measurement. This suggests that enhancements in the PR system and analysis may satisfactorily correct intersubject variability that currently limits the clinical use of PR devices and measurements.
Mar 2017 DOI 10.14302/issn.2326-0793.jpgr-17-1447
Factors that contribute to the onset of atherosclerosis may be elucidated by bioinformatic techniques applied to multiple sources of genomic and proteomic data. The results of genome wide association studies, such as the CardioGramPlusC4D study, expression data, such as that available from expression quantitative trait loci (eQTL) databases, along with protein interaction and pathway data available in Ingenuity Pathway Analysis (IPA), constitute a substantial set of data amenable to bioinformatics analysis. This study used bioinformatic analyses of recent genome wide association data to identify a seed set of genes likely associated with atherosclerosis. The set was expanded to include protein interaction candidates to create a network of proteins possibly influencing the onset and progression of atherosclerosis. Local average connectivity (LAC), eigenvector centrality, and betweenness metrics were calculated for the interaction network to identify top gene and protein candidates for a better understanding of the atherosclerotic disease process. The top ranking genes included some known to be involved with cardiovascular disease (APOA1, APOA5, APOB, APOC1, APOC2, APOE, CDKN1A, CXCL12, SCARB1, SMARCA4 and TERT), and others that are less obvious and require further investigation (TP53, MYC, PPARG, YWHAQ, RB1, AR, ESR1, EGFR, UBC and YWHAZ). Collectively these data help define a more focused set of genes that likely play a pivotal role in the pathogenesis of atherosclerosis and are therefore natural targets for novel therapeutic interventions.
Jan 2017 DOI 10.14302/issn.2379-7835.ijn-16-1408
Despite the agreed global and national stunting reduction targets, Uganda has made very little progress. Understanding context-specific risk factors for stunted growth is therefore pertinent to designing programs to address the problem. A cross-sectional study was conducted in 32 randomly selected villages in Buhweju district, Southwest Uganda. Data entry, cleaning and analysis were carried out using Statistical Package for Social Sciences (SPSS) version 21. A regression analysis was conducted to examine the associations between potential risk factors and stunted growth. The survey covered 256 households and anthropometric measurements were taken for 221 children aged 6–59 months. The majority of the households (66%) in the district were food insecure and had a low socioeconomic status (84%). The prevalence of stunting in Buhweju district was 51%, which is significantly higher than the regional and national averages. Only 28% of the children were exclusively breastfed in the first 6 months of life, and only 10% of them received the minimum acceptable diet (MAD). The findings of this study demonstrate that reductions in stunted growth at national or regional levels has not necessarily translated into similar trends in rural areas of Uganda. The notable contributors to stunting in these areas include morbidity, sub-optimal infant and young child feeding (IYCF) practices, low consumption of animal-source foods, food insecurity, lack of access to high-quality drinking water, sanitation and hygiene (WASH) facilities and poverty. Increased investment in both nutrition specific and sensitive interventions is therefore crucial to address these risk factors.
Dec 2016 DOI 10.14302/issn.2471-2140.jaa-16-1378
Methionine (Met) is a nutritionally essential amino acid and has been widely demonstrated to improve cellular oxidative balance and mediate oxidative stress. Met targets reactive oxygen species (ROS) directly by being oxidized to Met sulfoxide (MetO) 1. Met can be metabolized to cysteine (Cys) through transsulfuration pathway, which is further metabolized to glutathione (GSH), taurine, and hydrogen sulfide (H2S). All these metabolites exhibit antioxidant functions in various models (reviewed at 2). More recently, Met also has been demonstrated to enhance cellular oxidative tolerance via pentose phosphate pathway (PPP) 3, which contributes to the balance of cellular reducing power and accelerates the reduction reaction of MetO and GSH oxidative product GSSH back to Met and GSH.
Oct 2016 DOI 10.14302/issn.2572-3030.jcgb-16-1276
Human uterine leiomyosarcoma (LMS) is neoplastic malignancy that typically arises in tissues of mesenchymal origin. The identification of novel molecular mechanism leading to human uterine LMS formation and the establishment of new therapies has been hampered by several critical points. We earlier reported that mice with a homozygous deficiency for proteasome beta subunit 9 (PSMB9)/b1i, an interferon (IFN)-g inducible factor, spontaneously develop uterine LMS. The use of research findings of the experiment with mouse model has been successful in increasing our knowledge and understanding of how alterations, in relevant oncogenic, tumour suppressive, and signaling pathways directly impact sarcomagenesis. The IFN-g pathway is important for control of tumour growth and invasion and, has been implicated in several malignant tumours. In this study, experiments with human tissues revealed a defective PSMB9/b1i expression in human uterine LMS that was traced to the IFN-g pathway and the specific effect of somatic mutations of Janus kinase (JAK1) molecule or promoter region on the transcriptional activation of PSMB9/b1i gene. Understanding the molecular mechanisms of human uterine LMS may lead to identification of new diagnostic candidates or therapeutic targets in human uterine LMS.
Feb 2016 DOI 10.14302/issn.2329-9487.jhc-15-864
This article reviews heart–kidney signaling in heart failure, contrasting adaptive and maladaptive pathways. It discusses neurohormonal activation, fibrosis, and emerging therapeutic targets.
May 2015 DOI 10.14302/issn.2379-7835.ijn-14-603
Epigenetic mechanisms based on DNA methylation, histone modifications and RNA interference have recently showed important association to the development of a wide variety of diseases such as cancer, cardiovascular, metabolic, skin, autoimmune diseases and neurologic disorders. In the context of preventive aspects, the importance of nutrition on epigenetic function has been revealed. Therefore, drastic changes in dietary modifications may contribute to reduced disease risk. For instance, dietary intervention has been showed to affect DNA methylation in Alzheimer’s disease patients. Moreover, maternal high-fat diet can regulate gene expression through promoter histone modifications. Most importantly, RNA interference and particularly micro-RNA mediated regulation of gene expression has been linked to disease development. Remarkably, dietary intake has been demonstrated to significantly affect various miRNAs and their regulation on gene function. In this review, the relationship between epigenetics and disease and development of drugs based on epigenetic targets is presented as well as the influence of dietary intake on epigenetic mechanisms and its effect on disease prevention and therapy will be discussed.