Medical hypotheses最新文献

{"title":"Beyond antibiotics: 3d-transition metal ions − serum albumin −indocyanine green complex as a novel multifunctional NIR-responsive therapeutic platform for treating diabetic foot ulcer","authors":"Jayashree Roy,&nbsp;Indranil Banerjee","doi":"10.1016/j.mehy.2025.111628","DOIUrl":"10.1016/j.mehy.2025.111628","url":null,"abstract":"<div><div>Diabetic Foot Ulcer (DFU) is a severe chronic diabetes mellitus complication with delayed wound healing. A number of factors such as antibiotic-resistant bacterial infection, ischemia, matrix metalloproteinases (MMPs)- mediated degradation of granulating tissue, fibroblast senescence and hypoalbuminemia contribute to the severity of DFU. Present therapies are often found to be inactive since they fail to provide a comprehensive solution. To address this challenge, here we have hypothesized that a novel NIR-responsive phototherapeutic complex made with 3d-transition metal ions (preferably Zn²⁺), serum albumin (SA) and indocyanine green (ICG) will effectively work as a multifunctional therapeutic solution for the treatment of DFU. Under exposure to 808 nm Laser, ICG present in the Zn²⁺-SA-ICG complex will generate heat (photothermal effect) and ROS (photodynamic effect) which will kill the antibiotic-resistant bacteria in the wound milieu, Zn²⁺ released from the complex will activate the endothelial cells and help in angiogenesis, and SA will serve as a sacrificial substrate to nullify the degrading effect of MMPs and will activate fibroblast and compensate the hypoalbuminemia. The hypothesis can be tested through a series of biophysical experiments, in vitro microbial and cellular studies, in vivo analysis in MRSA bacteria-infected wound models in STZ-induced diabetic mice and finally through clinical trials. If successful, a new domain of clinical management for DFU will be opened. This will also facilitate the pathway of similar innovation for even better therapy.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111628"},"PeriodicalIF":2.1,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Could the administration of SGLT2i agents serve as a viable prophylactic approach against CNI-induced toxicities?","authors":"Yu-Hsiang Lin,&nbsp;Kuo-Jen Lin,&nbsp;Hsu-Han Wang","doi":"10.1016/j.mehy.2025.111626","DOIUrl":"10.1016/j.mehy.2025.111626","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111626"},"PeriodicalIF":2.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic Diet as a Brain-targeted Therapy in Psychogenic Nonepileptic Seizures: A Neuroimaging Findings-based Nutritional Hypothesis","authors":"Hamid Abbasi","doi":"10.1016/j.mehy.2025.111625","DOIUrl":"10.1016/j.mehy.2025.111625","url":null,"abstract":"<div><div>Psychogenic nonepileptic seizures (PNES) are non-epileptic events characterized by altered consciousness and motor activity that mimic epileptic seizures but lack abnormal brain discharges. Despite their prevalence, PNES remain diagnostically challenging, often coexisting with psychiatric and medical conditions. While ketogenic diets (KDs) have shown potential in treating neurological and psychiatric disorders, their impacts on PNES are underexplored. KDs, by shifting metabolism toward lipid oxidation and producing ketone bodies, offer neuroprotective and anti-inflammatory benefits, which may modulate brain connectivity and neurotransmitter balance. Neuroimaging studies, including electroencephalography, functional magnetic resonance imaging, and diffusion tensor imaging, have demonstrated altered brain activity and connectivity in PNES, particularly in regions responsible for emotional regulation, executive function, and motor control. The KD’s ability to restore these disrupted patterns through its anticonvulsant, anti-inflammatory, and neuroprotective properties makes it a potential treatment option for PNES. Preliminary studies, including a pilot trial, have shown promising results in reducing PNES frequency with KD use. However, further research with larger sample sizes and more rigorous methodologies is necessary to confirm these findings. This article proposes KD as a viable treatment for PNES, emphasizing the need for personalized, multidisciplinary approaches and the importance of using neuroimaging techniques and monitoring for potential metabolic complications to ensure long-term safety and efficacy.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111625"},"PeriodicalIF":2.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive sentinel lymph node biopsy on promotion of metastasis: An unexpected effect?","authors":"Lenan Shao ,&nbsp;Ariunbuyan Sukhbaatar ,&nbsp;Tsuyoshi Sugiura ,&nbsp;Tetsuya Kodama","doi":"10.1016/j.mehy.2025.111624","DOIUrl":"10.1016/j.mehy.2025.111624","url":null,"abstract":"<div><div>The paradigm of most metastases has been interpreted as an orderly pattern of spread from the primary tumor to sentinel lymph nodes (SLNs). SLN biopsy (SLNB) has long been considered the standard of care for staging malignancy and guiding treatment. However, the process of SLNB may have awakened or inadvertently provided more “seeds” and/or “soil” to the early anchored tumor foci in regional or distant sites from the “disturbed” SLNs. Furthermore, tumor-positive SLNs are excised, and the angiogenesis inhibition of the distant metastasis dormancy foci is attenuated by the cessation of anti-angiogenic extracellular matrix proteins released from the tumor foci in the SLNs. Here, we hypothesize that tumor-positive SLNB risks the promotion of metastasis. The strong correlation between positive SLNB and consequent metastasis is unexpected but can be fatal. Therefore, verifying the phenomenon and exploring the mechanisms involved is essential to allow steps to be taken to offset this highly potential iatrogenic complication.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111624"},"PeriodicalIF":2.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143800526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing hyperphosphatemia in dialysis patients with renal-specific oral nutritional supplements","authors":"Luka Grgar","doi":"10.1016/j.mehy.2025.111615","DOIUrl":"10.1016/j.mehy.2025.111615","url":null,"abstract":"<div><div>Hyperphosphatemia is a common issue in dialysis patients and a significant risk factor for mineral bone disorders, cardiovascular complications, and mortality. Various therapeutic modalities are available for managing high serum phosphorus, though their effectiveness remains limited. A combination of adequate dialysis, dietary restrictions on phosphorus intake, and phosphate binder therapy are routinely employed in the treatment. However, patient adherence to dietary recommendations and phosphate-binder therapy is often unsatisfactory. This paper proposes replacing phosphorus-rich meals with renal-specific oral nutritional supplements (RS-ONS). Specifically, RS-ONS with low phosphorus content should be used, which allows its use without the need for phosphate binders and with minimal fluid contribution. This approach could lower serum phosphorus levels, decrease the phosphate-binders pill burden, and improve patient compliance and quality of life.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111615"},"PeriodicalIF":2.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A theory on the pathogenesis of Leber hereditary optic neuropathy: Two hits and the role of light toxicity","authors":"Julio González-Martín-Moro ,&nbsp;Fernando J Gómez-Sanz ,&nbsp;Arturo Bravo-Nuevo ,&nbsp;Miguel Ángel García Cabezas","doi":"10.1016/j.mehy.2025.111623","DOIUrl":"10.1016/j.mehy.2025.111623","url":null,"abstract":"<div><div>Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder that leads to rapid, often irreversible central visual loss. While the mitochondrial inheritance of LHON was clarified in 1988, key aspects of its pathophysiology remain unexplained, particularly its selective impact on retinal ganglion cells (RGCs). Conventional hypotheses attribute this specificity to RGCs’ small, unmyelinated axons; however, these characteristics exist in other unaffected central nervous system (CNS) areas. Here, we propose that light exposure acts as a critical cofactor in mitochondrial dysfunction, contributing to RGC susceptibility in LHON. Unlike other CNS tissues, RGC axons in the retinal nerve fiber layer are highly exposed to light, which may disrupt mitochondrial function by generating reactive oxygen species (ROS) and increasing mitochondrial DNA (mtDNA) mutation rates. Given that retinal mitochondria contain numerous chromophores that may act as photosensitizers, the retina’s high metabolic activity combined with this unprotected light exposure could uniquely predispose RGCs to mitochondrial damage in LHON.</div><div>This hypothesis provides a novel framework for understanding LHON’s cell specificity and opens possibilities for broader applications, including other optic neuropathies where light exposure and mitochondrial vulnerability intersect. Future research should examine the impact of light protection on LHON progression and test for higher LHON prevalence in northern latitudes or seasonal shifts. Our approach underscores the need for further investigation into the role of environmental factors in LHON, opening a door to novel ways for prevention and intervention for patients with this neuropathy.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111623"},"PeriodicalIF":2.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “A hypothesis linking the Renin-Angiotensin, Kallikrein-Kinin systems, and disseminated coagulation in Covid-19” [Med. Hypothesis 192 (2024) 111488]","authors":"Paula Fernanda Ribas Neves ,&nbsp;Lisiê Valéria Paz ,&nbsp;Andrea Wieck ,&nbsp;Léder Leal Xavier","doi":"10.1016/j.mehy.2025.111603","DOIUrl":"10.1016/j.mehy.2025.111603","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111603"},"PeriodicalIF":2.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothesizing glucagon-like peptide 1 (GLP-1), agonists promote hypodopaminergia, resulting in heightened addictive reward-seeking and altered mood: Breaking the bubble and adding salt to a wound","authors":"Kenneth Blum ,&nbsp;Catherine A. Dennen ,&nbsp;Kai-Uwe Lewandrowski ,&nbsp;Alireza Sharafshah ,&nbsp;Albert Pinhasov ,&nbsp;Abdalla Bowirrat ,&nbsp;Igor Elman ,&nbsp;Jean Lud Cadet ,&nbsp;Eric R. Braverman ,&nbsp;Panayotis K. Thanos ,&nbsp;Milan Makale ,&nbsp;David Baron ,&nbsp;J.Wesson Ashford ,&nbsp;Brian Fuehrlein ,&nbsp;Nicole Avena ,&nbsp;Eliot Gardner ,&nbsp;Rajendra D. Badgaiyan ,&nbsp;Marjorie Gondré—Lewis ,&nbsp;Edward J. Modestino ,&nbsp;Jag Khalsa ,&nbsp;Mark S. Gold","doi":"10.1016/j.mehy.2025.111612","DOIUrl":"10.1016/j.mehy.2025.111612","url":null,"abstract":"<div><div>Recent articles have suggested that the agonistic effects of GLP-1 in alcohol use disorder and substance use disorder are mediated centrally, partly through the downregulation of dopamine signaling. This hypothesis, from a consortium of multidisciplinary scientists and clinicians, explores the role of GLP-1 receptor agonists as compounds with broad antiaddiction properties. Short-term dopamine downregulation is relevant in treating metabolic disorders to reduce hyperdopaminergia, which increases insulin resistance and decreases insulin secretion. Single-nuclei transcriptomics and Fluorescent in situ Hybridization (FISH) studies revealed that GLP-1Rs are expressed primarily on GABA neurons in the VTA. Scientists using in-vivo fiber photometry found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. However, to our knowledge, this is the first hypothesis to expose the potential of GLP-1 receptor agonists for heightened addictive reward-seeking behavior. Therefore, we caution against promoting chronic stimulation via GLP-1 agonists. Indeed, basic research findings have linked GLP-1 receptor agonists and several genes within the dopaminergic reward pathway. Therefore, stimulation of GLP-1 receptor agonists, especially chronically, can lead to the dysregulation of the dopaminergic pathway, which in turn can putatively cause depression, suicidality, and other mood disturbances. <em>We therefore hypothesize that while employing GLP-1 agonism offers therapeutic benefits in instances of recognized hyperdopaminergia, it could be detrimemtal in patients with hypodopaminergia at risk for SUD.</em></div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111612"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle fatigue and interference phenomenon during concurrent aerobic and strength training: An alternative hypothetical model","authors":"Benedito Sérgio Denadai,&nbsp;Camila Coelho Greco","doi":"10.1016/j.mehy.2025.111614","DOIUrl":"10.1016/j.mehy.2025.111614","url":null,"abstract":"<div><div>Concurrent training, defined as the combination of strength and aerobic exercise in a periodized program, has been shown to be important in both health and athletic performance contexts. Prescribing concurrent training is challenging because some studies have shown that improvements in strength and muscle mass may be attenuated when compared to strength training alone (i.e., the interference phenomenon). In a previous theoretical model, primarily based on manipulating training intensity, training zones were proposed to either maximize (aerobic training: 95–100 % VO₂max + resistance training: 3–4 sets of &gt; 10 maximal repetitions; RM) or minimize (30 to 60 min of moderate-intensity continuous training; MICT + resistance training performed at different % RM) the interference phenomenon. The model proposes that the primary location of adaptations promoted by MICT (i.e., central − cardiovascular) differs from those promoted by strength training protocols (neural and/or peripheral adaptations), thereby attenuating the interference effect on muscle strength. However, there is substantial evidence that the peripheral adaptations (muscle oxidative capacity) from endurance training are not dependent on exercise intensity. In this paper, we propose an alternative hypothetical model of the concurrent training interference phenomenon based on the acute hypothesis (i.e., residual fatigue). We discuss the strengths of the model, considering moderator variables (sex, within-session exercise order, between-mode recovery, endurance training volume, intensity, and modality), which can maximize or minimize the interference phenomenon.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111614"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota as a potential mechanism besides ketone bodies in Ameliorating Parkinson’s disease symptoms with the ketogenic diet","authors":"Xian-Mu Luo ,&nbsp;Jun Luo ,&nbsp;Ling-Yong Zeng ,&nbsp;Chun-Ling Chi","doi":"10.1016/j.mehy.2025.111609","DOIUrl":"10.1016/j.mehy.2025.111609","url":null,"abstract":"<div><div>Current research indicates that the ketogenic diet effectively alleviates symptoms in Parkinson’s disease (PD) patients, presenting a promising novel therapy. The prevailing view attributes the ketogenic diet’s efficacy in PD improvement to ketone bodies. Studies in epilepsy have demonstrated that the ketogenic diet improves epilepsy by modulating gut microbiota. Inspired by this, we hypothesize that the gut microbiota mediates the ketogenic diet’s alleviation of PD symptoms. On one hand, evidence from epilepsy and Alzheimer’s research supports the ketogenic diet’s influence on gut microbiota. On the other hand, PD studies indicate that gut microbiota can influence PD progression. Potential mechanisms may involve the production of neuroprotective metabolites, the modulation of the brain-gut microbiota axis, and the reduction of pathological protein aggregation. This hypothesis can be tested through animal models or clinical experiments. If validated, it could strongly support the widespread application of ketogenic diet therapy in PD and signify gut microbiota as a target for PD treatment, fostering simple and effective therapeutic approaches.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111609"},"PeriodicalIF":2.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}