Exploration of medicine最新文献

{"title":"Oxidative stress, inflammation, dysfunctional redox homeostasis and autophagy cause age-associated diseases","authors":"P. Sobhon, Gavin Savedvanich, S. Weerakiet","doi":"10.37349/emed.2023.00124","DOIUrl":"https://doi.org/10.37349/emed.2023.00124","url":null,"abstract":"Aging and age-associated diseases (AADs) are growing risk factors in societies worldwide. During aging, there is an accumulation of excessive oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] due to dysfunctional mitochondria, dysregulated catalytic activities of cytochrome P450 (CYP), nicotinamide adenine dinucleotide (NAD) phosphate [NADP(H)] oxidase (NOX), cyclooxygenases, and nitric oxide synthases (NOS) over the threshold of physiological levels, creating oxidative stress (OS). Excessive ROS and RNS oxidize, break, denature, and sometimes cause aggregations of key cellular components including DNA, proteins, and lipids. Normally, these denatured molecules and their aggregates are eliminated by autophagy (AP) and ubiquitin-proteosome system (UPS). However, these two proteostatic mechanisms are impaired as age progresses. As a result, these abnormal molecules turn into damage-associated molecular patterns (DAMPs), recognized as non-self by immune cells, leading to systemic chronic inflammation (SCI), which together with OS are the major causes of aging and AADs. Therefore, instead of trying to prevent and cure AADs individually, the logical approach should be the restoration of redox homeostasis by the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway which can prevent the damaging effect of OS and the upregulation of AP and UPS to eliminate DAMPs, and together they attenuate SCI to lessen the effect of inflammation. The central regulators, adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and Sestrins, synergistically control the restoration of the redox homeostasis by activating Nrf2, the upregulation of AP-UPS, and the inhibition of SCI. The activation of these central regulators can be achieved by exercise, caloric restriction (CR), and intakes of certain CR mimetic natural compounds. Consequently, the activations of these regulators may lead to the prevention and/or attenuation of the AADs.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45339039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking analysis of peptide-based antiviral agents against SARS-CoV-2 main protease: an approach towards drug repurposing","authors":"A. Chaurasiya, Abhimannu Shome, P. Chawla","doi":"10.37349/emed.2023.00123","DOIUrl":"https://doi.org/10.37349/emed.2023.00123","url":null,"abstract":"Aim:\u0000\u0000Utilizing the therapeutic potentials of previously approved medications against a new target or pharmacological response is known as drug repurposing. The health and scientific communities are under continual pressure to discover new compounds with antiviral potential due to the rising reports of viral resistance and the occurrence and re-emergence of viral outbreaks. The use of antiviral peptides has emerged as an intriguing option in this search. Here, this article includes the current United States Food and Drug Administration (FDA)-approved antiviral peptides that might be enforced for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and carried out docking study of the viral protease inhibitors.\u0000Methods:\u0000\u0000In silico techniques like molecular docking was carried out using Autodock Vina software.\u0000Results:\u0000\u0000The molecular docking studies of peptide-based antiviral agents against SARS-CoV-2 [Protein Data Bank (PDB) ID: 7P35] using docking software AutoDockTools 1.5.6. Among all the docked ligands, compound velpatasvir showed interaction with residues ILE213, GLN256, LEU141, GLN189, GLU166, HIS41, CYS145, and ASN142, and displayed the highest docking score of –8.2 kcal/mol. This medication could be a novel treatment lead or candidate for treating SARS-CoV-2.\u0000Conclusions:\u0000\u0000To conclude, a docking study of peptide based antiviral compounds for their binding mode in the catalytic domain of SARS-CoV-2 receptor is reported. On molecular docking, the compounds have showed remarkable binding affinity with the amino acids of receptor chain A. The compounds occupied the same binding cavity as the reference compound maintaining the interactions with conserved amino acid residues essential for significant inhibitory potential, especially for compound velpatasvir with binding score of –8.2 kcal/mol.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48024197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities and trends in suicidal ideations for inflammatory bowel disease hospitalizations: a decade-long national database analysis","authors":"Hassam Ali, Pratik Patel, R. Dhillon, Shiza Sarfraz, S. Poola, L. Smith-Martinez, Karina Fatakhova, R. Rajapakse","doi":"10.37349/emed.2023.00122","DOIUrl":"https://doi.org/10.37349/emed.2023.00122","url":null,"abstract":"Aim: Patients with inflammatory bowel disease (IBD) are more likely to develop anxiety or depression. The study aimed to describe the trends and disparities of suicidal ideation (SI) in hospitalized IBD patients.\u0000Methods: A retrospective study was conducted using the National Inpatient Sample (NIS) database, to analyze SI among the IBD hospitalizations from 2009 to 2019. Bivariate analysis was conducted using a chi-square test for categorical variables and an independent t-test for continuous variables. For prevalence, the trend over time was evaluated using the score test.\u0000Results: There were 1,724 IBD hospitalizations with SI for the study period. There was a male (53.8%) and white race (74.2%) predominance. The mean age was 41.47 ± 0.25 years. The hospital stay decreased for IBD hospitalizations with SI from 7.97 days in 2009 to 7.57 days in 2019 (P < 0.001). The mean hospital charge increased from $44,664 in 2009 to $66,639 in 2019 (P < 0.001). The prevalence of SIs increased from 0.17% in 2009 to 0.29% in 2019 (P < 0.001). The mean age of these hospitalizations increased from 38 years in 2009 to 42.3 years in 2019 (P = 0.02). The prevalence of generalized anxiety disorder (GAD) increased from < 1% in 2009 to 12.19% in 2019 (P < 0.001). The prevalence of depression increased from 18.04% in 2009 to 51.21% in 2019 (P < 0.001). Inpatient mortality increased from 0% in 2009 to 2.43% in 2019 (P = 0.024). Among IBD hospitalizations, the male gender had a higher association with SIs than females (odds ratio 1.32 [95% confidence intervals (CI) 1.06–1.66], P = 0.014).\u0000Conclusions: There is a rise of SI among the IBD population. Specialized protocols should be in place in clinical settings and communities to identify and assess high-risk patients.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45659771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An association study of the PNPLA3 I148M polymorphism (rs738409) with serum lipids in patients with dyslipidemia","authors":"D. Ioannidou, E. Makri, S. Polyzos, Charikleia Ntenti, D. Agapakis, G. Germanidis, A. Goulas","doi":"10.37349/emed.2023.00121","DOIUrl":"https://doi.org/10.37349/emed.2023.00121","url":null,"abstract":"Aim: One single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene has been considered a major genetic risk factor of nonalcoholic fatty liver disease (NAFLD). Data have indicated that NAFLD is related to insulin resistance and dyslipidemia, but whether rs738409 is associated with circulating lipid and lipoproteins is not fully elucidated. The main aim of this study was to assess the association of rs738409 with lipid and lipoprotein levels in patients with dyslipidemia.\u0000Methods: This was a post-hoc analysis of a study in patients with dyslipidemia recruited on an outpatient basis. Morning blood samples were collected after a 12-h fast. Genomic DNA was extracted from whole-blood samples.\u0000Results: One hundred seventy-five patients with dyslipidemia were included (97 women). Lipid levels [total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] or glycosylated hemoglobin (HbA1c) were not associated with the SNP, even after adjustment for gender, body mass index (BMI) and type 2 diabetes mellitus (T2DM), using either the additive (CC vs. CG vs. GG) or the dominant (CC vs. GG + CG) inheritance model. When data were stratified for obesity, significant associations between the variant and TC (P = 0.014) or LDL-C levels (P = 0.046) in the non-obese were observed. Pairwise comparison revealed significant changes only in TC between CC and CG genotypes (P = 0.012).\u0000Conclusions: No association was shown between rs738409 SNP and lipid/lipoprotein levels in patients with dyslipidemia. In subgroup analysis, TC was higher in non-obese, but not in obese, patients with CC, compared to CG carriers.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43670024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in metabolic status of healthy individuals with and without obesity during transition from adolescence to young adulthood","authors":"S. Sonoli, V. Kothiwale, Reshma D. Channashetti","doi":"10.37349/emed.2023.00120","DOIUrl":"https://doi.org/10.37349/emed.2023.00120","url":null,"abstract":"Aim: Extensive research is carried out throughout the world in healthy persons with obesity phenotype in concern with prevalence, metabolic profiling, etc. To the best of the authors’ knowledge, not many studies have investigated the status of adiponectin, specific inflammatory changes, oxidative damage in healthy adolescents and young adults with obesity. Present study was undertaken in adolescents and young adults of urban population in a district of North Karnataka, India, in a view to understand relationship between hormone adiponectin, oxidative stress markers like C3, C4, high sensitivity C-reactive protein (hs-CRP) in non-hypertensive, non-diabetic, euthyroid individuals with and without obesity.\u0000Methods: Participant selection was done using cluster sampling technique. Participating adolescents and young adults, each with and without obesity were included in the study. Screening of participants for diabetes, hypertension, and thyroid disorders was done, their serum level of adiponectin, hs-CRP, C3, C4, ceruloplasmin (Cp), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TAC) were estimated using standardized methods in National Accreditation Board for Testing and Calibration Laboratories (NABL) laboratory.\u0000Results: Adiponectin (young adults lower than adolescents, P = 0.01) levels were low, while hs-CRP and Cp (young adults higher than adolescents, P = 0.01) levels were high with increasing age in non-obese. While in persons having obesity, aging adiponectin levels were low while hs-CRP, C3, Cp levels were high significantly. Females without obesity had significantly higher values of C3 than males. Adiponectin showed higher levels in females than males, however, statistical significance could not be achieved (P = 0.308). While females with obesity, exhibited statistically lower levels of adiponectin, and higher levels of C3 and C4.\u0000Conclusions: Being non-diabetic and non-hypertensive yet obese, tagged by one time of assay, does not suffice to be categorized as healthy. Healthy young adults with obesity are exhibiting lower levels of adiponectin and higher levels of inflammatory and oxidative stress markers compared to adolescents with obesity. This implies, the so categorized “healthy obese” participants are in a phase of transition towards an unhealthy state.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45329518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-widefield imaging technologies in the peripheral retinal pathologies","authors":"L. Balyen","doi":"10.37349/emed.2023.00119","DOIUrl":"https://doi.org/10.37349/emed.2023.00119","url":null,"abstract":"","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43314498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality by design based development of nanostructured lipid carrier: a risk based approach","authors":"Tausif Alam","doi":"10.37349/emed.2022.00118","DOIUrl":"https://doi.org/10.37349/emed.2022.00118","url":null,"abstract":"The aim of this review is to discuss the development of nanostructured lipid carrier (NLC) by the application of quality by design (QbD). QbD started with the evolution of the quality concept and slow adaptation of quality guidelines, which has now become a regulatory requirement. In this review, brief history and elements of QbD including risk assessment (RA) have been discussed followed by the design of experiments (DoEs) that acts as a tool to analyze the input whose variation can optimize the output with the desired goal. NLC is a versatile delivery system as researchers widely use it to administer therapeutics with different physicochemical properties. The surface of NLC can be modified, making it a suitable delivery system with targeting potential for therapeutics. Implementation of QbD provides a high-quality robust formulation that can consistently meet the patient’s requirement throughout its life cycle without compromising the safety and effectiveness of the drug and delivery system. This review discusses QbD concepts followed by the systematic development of NLC by the application of DoE. Process analytical technology (PAT) and six sigma concepts have also been included which can benefit in the development of optimized NLC.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46654548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right atrial thrombus, junctional tachycardia, and critical lower limb ischemia: three rare complications of severe acute respiratory syndrome coronavirus 2 infection","authors":"Said Makani, A. Laarje, Meryem Mabrouk, Y. Zaid, Malak Chahid, Zaynab Hifdi, Meriem Azhari, C. Elkettani, H. Belmir, Youssef Tijani","doi":"10.37349/emed.2022.00115","DOIUrl":"https://doi.org/10.37349/emed.2022.00115","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can engender multi-system inflammatory syndrome. Its main symptoms are cardiovascular and thromboembolic problems that can develop into severe complications. The present case is about a 55-year-old patient who was admitted for critical ischemia of the right lower limb and necrosis of the right forefoot. The patient was infected with coronavirus disease 2019 (COVID-19) one month before her admission. The patient also has cardiovascular risks including type 2 diabetes and hypertension. The performance of ultrasounds revealed a thrombus in the right atrium and the pulmonary artery, and arteriography detected an occlusion of the right popliteal joint for which she had an endovascular recanalization and amputation of the right forefoot. This case highlights that SARS-CoV-2 infection could be considered a serious cardiovascular disease requiring cardiovascular explorations to initiate hospital management and avoid severe complications.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49570790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant and photoprotective potential of Polypodium leucotomos","authors":"R. Cruz, Sharon Velásquez Arévalo, Anas Rashid, Marco Rolando Aronés Jara, M. S. Prado","doi":"10.37349/emed.2022.00117","DOIUrl":"https://doi.org/10.37349/emed.2022.00117","url":null,"abstract":"In recent years, Polypodium leucotomos has emerged with a great interest for having medicinal and therapeutic potential. It is producing very promising results due to the presence of antioxidant and photoprotective properties. Electronic libraries and databases, including Scopus, PubMed, Google Scholar, Science Direct, and Web of Science were searched to identify relevant studies; 79 publications contributed to this review regarding Polypodium leucotomos botanical aspects, chemical composition, antioxidant and photoprotective activity. It is used in complementary and alternative therapies with various pharmaceutical dosage forms (systemic or topical). Thanks to the composition of phytochemical constituents present in the leaves and rhizomes which confer antioxidant and photoprotective activity that has clinical therapeutic potential to be used as systemic and topical sunscreen of natural origin for the prevention of different types of skin diseases caused by harmful ultraviolet A and ultraviolet B radiations. However, more studies are needed in the future to test the ability and enhance the capacity of sunscreen and sunblock in cosmetic formulations. To conclude, it is recommended to carry out scientific studies based on different analytical methods to evaluate the phytoconstituents potential and to develop stable pharmaceutical formulations according to the skin phototype.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69832968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incursions by severe acute respiratory syndrome coronavirus-2 on the host anti-viral immunity during mild, moderate, and severe coronavirus disease 2019 disease","authors":"Saksena Nitin, Bonam Srinivasa R., Miranda-Saksena Monica, Cardoso Thyago H.","doi":"10.37349/ei.2022.00084","DOIUrl":"https://doi.org/10.37349/ei.2022.00084","url":null,"abstract":"The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the human host can lead to various clinical manifestations, from symptomless carriers to mild to moderate to severe/critical illness. Therefore, the clinical classification of SARS-CoV-2 disease, based on severity, is a reliable way to predict disease states in SARS-CoV-2 infection. Recent studies on genomics, transcriptomics, epigenomics, and immunogenomics, along with spatial analysis of immune cells have delineated and defined the categorization of these disease groups using these high throughout technologies. These technologies hold the promise of providing not only a detailed but a holistic view of SARS-CoV-2-led pathogenesis. The main genomic, cellular, and immunologic features of each disease category, and what separates them spatially and molecularly are discussed in this brief review to provide a foundational spatial understanding of SARS-CoV-2 immunopathogenesis.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48114841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}